Lujan-Fryns syndrome
Encyclopedia
Lujan–Fryns syndrome also referred to as X-linked mental retardation with Marfanoid habitus and Lujan syndrome, is an X-linked
genetic disorder
that causes mild to moderate mental retardation
and features described as Marfanoid habitus
, referring to a group of physical characteristics similar to those found in Marfan syndrome
. These features include a tall, thin stature and long, slender limbs. LFS is also associated with psychopathology
and behavioral
abnormalities, and it exhibits a number of malformations affecting the brain
and heart
. The disorder is inherited in an X-linked dominant
manner, and is attributed to a missense mutation
in the MED12
gene. There is currently no treatment or therapy for the underlying MED12 malfunction, and the exact etiology
of the disorder remains unclear.
anomaly seen with LFS is agenesis of the corpus callosum
, an error of embryo
nic development in which the corpus callosum
(a structure of the mammal
ian brain
composed of nerve
s that allows communication between the left and right cerebral hemispheres
) is not present. Among a number of adverse neurological effects sometimes found with an absence of the corpus callosum, mental retardation has been shown to occur at a rate of approximately 73 percent. A correlation between agenesis of the corpus callosum and mental retardation in LFS, however, has not been suggested.
, and LFS is considered as one of a number of genetic disorders associated with autism
. Additional alterations of psychopathology with behavioral manifestations that have been observed in LFS include: psychotic behavior
, schizophrenia
, hyperactivity and attention-deficit hyperactivity disorder
, aggression
, oppositional defiant disorder
, obsessive compulsive disorder, extreme shyness
, learning disability
, cognitive impairment
, short-term memory
deficit, low frustration tolerance
, social dysfunction
, lack of impulse control
, eating disorder
and associated malnutrition
, attributed to psychogenic
loss of
appetite
; and pyromania
.
While psychiatric
conditions like these are to be expected with LFS, there have also been cases of the disorder with some preservation of mental and behavioral abilities, such as problem solving
, reasoning and normal intelligence
.
The psychopathology of LFS usually exhibits schizophrenia. When schizophrenia is diagnosed in an individual known to be affected by mental retardation, LFS may be considered in the differential diagnosis
of schizophrenia, with confirmation of etiology through appropriate psychiatric and genetic evaluation methods.
.
In LFS, specific features identified as marfanoid include: a long, narrow face; tall, thin stature
; long, slender limbs
, finger
s and toe
s (not unlike arachnodactyly
) with joint
hyperextensibility, shortened halluces
(the big toes) and long second toes.
The diagnosis of marfanoid habitus in LFS is often delayed because many of the physical features and characteristics associated with it are usually not evident until adolescence
.
ry hypoplasia
(underdevelopment of the upper jaw
bone
), a small mandible (lower jaw bone) and receding chin
, a high-arched palate
(the roof of the mouth), with crowding and misalignment of the upper teeth; macrocephaly
(enlarged skull
) with a prominent forehead
, hypernasal speech
(voice
), a long nose
with a high, narrow nasal bridge
; a deep, short philtrum
(the indentation in the upper lip, beneath the nose), low-set ear
s with some apparent retroversion
, hypotonia
(decreased muscle
tone
), pectus excavatum
(a malformity of the chest
), slightly enlarged to normal testicular
size in males, and seizure
s.
Hypernasal speech, or"hypernasality" , is primarily the result of velopharyngeal insufficiency
, a sometimes congenital
aberration in which the velopharyngeal sphincter
allows too much air into the nasal cavity
during speech. In LFS, hypernasality may also be caused by failure of the soft palate
and uvula to reach the back wall of the pharynx
(the interior cavity of the throat
where swallowing
generally occurs) during speech, a condition that can be associated with a submucosa
l cleft palate.
have been noted in several LFS cases, the most significant being dilation of the aortic root, a section of the ascending aorta
. Aortic root dilation (enlargement) is associated with a greatly increased risk of dissection
of the aortic
wall, resulting in aortic aneurysm
. As this presents a possible life-threatening consequence of LFS, routine cardiac
evaluation methods such as echocardiogram are implemented when the disorder is first diagnosed, along with MRI
scans of the brain to screen for suspected agenesis of the corpus callosum. Additional effects on the heart that have been reported with LFS are ventricular
and atrial septal defect
.
in the MED12
gene, located on the human X chromosome
, has been established as the cause of LFS. Missense mutations are genetic point mutation
s in which an amino acid
codon that does not belong in the nucleotide sequence of a particular protein
is erroneously substituted for an amino acid that is supposed to be included in the sequence, at a specific location. The missense mutation in the MED12 gene, that causes LFS, is identified as p.N1007S. This indicates that the amino acid asparagine
, normally located at position 1007 along the MED12 sequence, has been mistakenly replaced by serine
. This mutation in MED12 causes incorrect expression and activity of the protein it encodes, resulting in the disorder.
MED12, or mediator of RNA polymerase II trancription, subunit 12 homolog of S. cerevisiae, is one of several subunits in the mammalian mediator complex
, which regulates RNA polymerase II
during mRNA
transcription
.
The Mediator complex is required for polymerase II transcription and acts as a bridge between the polymerase II enzyme and different gene-specific transcription factors. Mediator can contain up to 30 subunits, but some of the subunits are only required for regulation of transcription in particular tissues or cells. Currently, the exact mechanism by which dysfunction of MED12 results in LFS and its associated neuropsychopathic and physical characteristics is unclear. Marfanoid habitus, a highly arched palate and several other features of LFS can be found with Marfan syndrome, a connective tissue disorder. The finding of aortic root dilation in both disorders suggests that a mutation in an unspecified connective tissue
regulating gene may contribute to the etiology of LFS.
A number of interesting experimental results have been obtained by studying MED12 mutations in the zebrafish, an animal model
representing vertebrate
s. In zebrafish, a mutation in MED12 was found to be responsible for the mutant motionless (mot). Zebrafish with the mot mutation have neuronal and cardiovascular defects, although not all types of neurons are affected. Introduction of human MED12 mRNA into the zebrafish restores normal development. MED12 is also a critical coactivator
for the gene SOX9
, which is involved in the developmental regulation of neurons, cartilage
and bone
. In the zebrafish, MED12 defects cause maldevelopment of vertebrate embryonic structures such as the neural crest
, which would alter function of the autonomic
and peripheral nervous system
s; and they also cause malformations of cell type
s serving as precursors to cartilage
and bone
, such as osteocyte
s. Some features found in LFS, like agenesis of the corpus callosum and cartilage-related craniofacial anomalies, are similar to defects found in zebrafish with MED12 and associated mutations.
manner. This means the defective gene responsible for the disorder (MED12) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity
in males than females. This phenomenon is thought to occur with LFS.
As the X chromosome is one of the sex chromosomes (the other being the Y chromosome
), X-linked
inheritance is determined by the gender
of the parent carrying a specific gene and can often seem complex. This is because, typically, female
s have two copies of the X-chromosome, while male
s have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.
In LFS, X-linked dominant inheritance was suspected, as boy and girl siblings in one family both exhibited the disorder. A scenario such as this would also be possible with X-linked recessive
inheritance, but in this particular case report, the girl was believed to be a manifesting heterozygote., carrying one copy of the mutated gene.
Sporadic cases of LFS, where the disorder is present in an individual with no prior family history of it, have also been reported in a small number of affected males.
in the short arm
of chromosome 5. Deletion of this area of chromosome 5 is associated with mental retardation, psychotic behavior, autism, macrocephaly and hypernasal-like speech, as well as the disorder Cri du chat syndrome. Fryns (2006) suggests a detailed examination of chromosome 5 with FISH
should be performed as part of the differential diagnosis of LFS.
Mutations in the UPF3B
gene, also found on the X chromosome, are another cause of X-linked mental retardation. UPF3B is part of the nonsense-mediated mRNA decay
(NMD) complex, which performs mRNA surveillance
, detecting mRNA sequences that have been erroneously truncated (shortened) by the presence of nonsense mutation
s. Mutations in UPF3B alter and prevent normal function of the NMD pathway, resulting in translation and expression of truncated mRNA sequences into malfunctioning proteins that can be associated with developmental errors and mental retardation. Individuals from two families diagnosed with LFS and one family with FGS were found to have mutations in UPF3B, confirming that the clinical presentations of the different mutations can overlap.
of LFS, another disorder that exhibits some features and symptoms of LFS and is also associated with a missense mutation of MED12 is Opitz-Kaveggia syndrome
(FGS). Common features shared by both LFS and FGS include X-linked mental retardation, hyperactivity, macrocephaly, corpus callosum agenesis and hypotonia. Notable features of FGS that have not been reported with LFS include excessive talkativness, consistent strength in socialization skills, imperforate anus
(occlusion of the anus
) and ocular hypertelorism
(extremely wide-set eye
s).
Whereas LFS is associated with missense mutation p.N1007S, FGS is associated with missense mutation p.R961W. As both disorders originate from an identical type of mutation in the same gene, while exhibiting similar, yet distinct characteristics; LFS and FGS are considered to be allelic
. In the context of MED12, this suggests that the phenotype of each disorder is related to the way in which their respective mutations alter the MED12 sequence and its function.
s J. Enrique Lujan and Jean-Pierre Fryns. The initial observation of suspected X-linked mental retardation with Marfanoid features and craniofacial effects such as a high-arched palate
was described by Lujan et al. in 1984. In the report, four affected male members of a large kindred
(consanguinous
family) were noted. Additional investigations of combined X-linked mental retardation and Marfanoid habitus in other families, including two brothers, were reported by Fryns et al., beginning in 1987. The disorder soon became known as Lujan–Fryns syndrome.
Sex linkage
Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...
genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that causes mild to moderate mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
and features described as Marfanoid habitus
Marfanoid
Marfanoid is a term used to describe a constellation of findings including long limbs, arachnodactyly and hyperlaxity.Associated conditions include:* Marfan syndrome...
, referring to a group of physical characteristics similar to those found in Marfan syndrome
Marfan syndrome
Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....
. These features include a tall, thin stature and long, slender limbs. LFS is also associated with psychopathology
Psychopathology
Psychopathology is the study of mental illness, mental distress, and abnormal/maladaptive behavior. The term is most commonly used within psychiatry where pathology refers to disease processes...
and behavioral
Human behavior
Human behavior refers to the range of behaviors exhibited by humans and which are influenced by culture, attitudes, emotions, values, ethics, authority, rapport, hypnosis, persuasion, coercion and/or genetics....
abnormalities, and it exhibits a number of malformations affecting the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
and heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. The disorder is inherited in an X-linked dominant
X-linked dominant
X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type...
manner, and is attributed to a missense mutation
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
in the MED12
MED12
Mediator of RNA polymerase II transcription, subunit 12 homolog , also known as MED12, is a human gene found on the X chromosome...
gene. There is currently no treatment or therapy for the underlying MED12 malfunction, and the exact etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of the disorder remains unclear.
Characteristics
Mental retardation in LFS usually ranges from mild to moderate, but severe cases have also been reported. A relatively common brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
anomaly seen with LFS is agenesis of the corpus callosum
Agenesis of the corpus callosum
Agenesis of the corpus callosum is a rare birth defect in which there is a complete or partial absence of the corpus callosum. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally,...
, an error of embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
nic development in which the corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
(a structure of the mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
composed of nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
s that allows communication between the left and right cerebral hemispheres
Cerebral hemisphere
A cerebral hemisphere is one of the two regions of the eutherian brain that are delineated by the median plane, . The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres has an outer layer of grey matter called the cerebral cortex that is...
) is not present. Among a number of adverse neurological effects sometimes found with an absence of the corpus callosum, mental retardation has been shown to occur at a rate of approximately 73 percent. A correlation between agenesis of the corpus callosum and mental retardation in LFS, however, has not been suggested.
Psychiatric manifestations
Psychopathology and related behavioral abnormalities are typically seen in LFS, and they may be considered in the diagnosis of the disorder. The most common of these in LFS is an autism-like spectrum disorderAutism spectrum
The term "autism spectrum" is often used to describe disorders that are currently classified as pervasive developmental disorders. Pervasive developmental disorders include autism, Asperger syndrome, Childhood disintegrative disorder, Rett syndrome and Pervasive Developmental Disorder Not Otherwise...
, and LFS is considered as one of a number of genetic disorders associated with autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
. Additional alterations of psychopathology with behavioral manifestations that have been observed in LFS include: psychotic behavior
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, hyperactivity and attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
, aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
, oppositional defiant disorder
Oppositional defiant disorder
Oppositional defiant disorder is a diagnosis described by the Diagnostic and Statistical Manual of Mental Disorders as an ongoing pattern of disobedient, hostile and defiant behavior toward authority figures which goes beyond the bounds of normal childhood behavior...
, obsessive compulsive disorder, extreme shyness
Shyness
In humans, shyness is a social psychology term used to describe the feeling of apprehension, lack of comfort, or awkwardness experienced when a person is in proximity to, approaching, or being approached by other people, especially in new situations or with unfamiliar people...
, learning disability
Learning disability
Learning disability is a classification including several disorders in which a person has difficulty learning in a typical manner, usually caused by an unknown factor or factors...
, cognitive impairment
Cognitive dysfunction
Cognitive dysfunction is defined as unusually poor mental function, associated with confusion, forgetfulness and difficulty concentrating...
, short-term memory
Short-term memory
Short-term memory is the capacity for holding a small amount of information in mind in an active, readily available state for a short period of time. The duration of short-term memory is believed to be in the order of seconds. A commonly cited capacity is 7 ± 2 elements...
deficit, low frustration tolerance
Low frustration tolerance
Proponents of Albert Ellis' Rational Emotive Behavioral Therapy cite a construct or concept they call low frustration tolerance, or "short-term hedonism" in order to partly explain behaviors like procrastination and certain other apparently paradoxical or self-defeating behavior...
, social dysfunction
Social anxiety disorder
Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
, lack of impulse control
Impulse control disorder
Impulse control disorder is a set of psychiatric disorders including intermittent explosive disorder, kleptomania, pathological gambling, pyromania , and three body-focused repetitive or compulsive behaviors of trichotillomania , onychophagia and dermatillomania...
, eating disorder
Eating disorder
Eating disorders refer to a group of conditions defined by abnormal eating habits that may involve either insufficient or excessive food intake to the detriment of an individual's physical and mental health. Bulimia nervosa, anorexia nervosa, and binge eating disorder are the most common specific...
and associated malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
, attributed to psychogenic
Psychogenic disease
A psychogenic disease is a set of symptoms or complaints whose origin likely lies within the complex interactions of the frontal lobes of the brain and the system in which the complaint manifests...
loss of
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...
; and pyromania
Pyromania
Pyromania in more extreme circumstances can be an impulse control disorder to deliberately start fires to relieve tension or for gratification or relief. The term pyromania comes from the Greek word πῦρ . Pyromania and pyromaniacs are distinct from arson, the pursuit of personal, monetary or...
.
While psychiatric
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
conditions like these are to be expected with LFS, there have also been cases of the disorder with some preservation of mental and behavioral abilities, such as problem solving
Problem solving
Problem solving is a mental process and is part of the larger problem process that includes problem finding and problem shaping. Consideredthe most complex of all intellectual functions, problem solving has been defined as higher-order cognitive process that requires the modulation and control of...
, reasoning and normal intelligence
Intelligence
Intelligence has been defined in different ways, including the abilities for abstract thought, understanding, communication, reasoning, learning, planning, emotional intelligence and problem solving....
.
The psychopathology of LFS usually exhibits schizophrenia. When schizophrenia is diagnosed in an individual known to be affected by mental retardation, LFS may be considered in the differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
of schizophrenia, with confirmation of etiology through appropriate psychiatric and genetic evaluation methods.
Marfanoid habitus
LFS is clinically distinguished from other X-linked forms of mental retardation by the accompanying presence of marfanoid habitus. Marfanoid habitus describes a group of physical features common to Marfan syndrome. Including Marfan syndrome and LFS, marfanoid features of this type have also been observed with several other disorders, one of which is multiple endocrine neoplasia type 2Multiple endocrine neoplasia type 2
Multiple endocrine neoplasia type 2 is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant . They generally occur in endocrine organs Multiple endocrine neoplasia type 2 (also known as "Pheochromocytoma and amyloid producing medullary...
.
In LFS, specific features identified as marfanoid include: a long, narrow face; tall, thin stature
Human height
Human height is the distance from the bottom of the feet to the top of the head in a human body standing erect.When populations share genetic background and environmental factors, average height is frequently characteristic within the group...
; long, slender limbs
Limb (anatomy)
A limb is a jointed, or prehensile , appendage of the human or other animal body....
, finger
Finger
A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates....
s and toe
Toe
Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being digitigrade. Humans, and other animals that walk on the soles of their feet, are described as being plantigrade; unguligrade animals are those that walk on hooves at the tips of...
s (not unlike arachnodactyly
Arachnodactyly
Arachnodactyly or achromachia, is a condition in which the fingers are abnormally long and slender in comparison to the palm of the hand...
) with joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
hyperextensibility, shortened halluces
Hallux
In tetrapods, the hallux is the innermost toe of the foot. Despite its name it may not be the longest toe on the foot of some individuals...
(the big toes) and long second toes.
The diagnosis of marfanoid habitus in LFS is often delayed because many of the physical features and characteristics associated with it are usually not evident until adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
.
Craniofacial abnormalities
Craniofacial and other features of LFS include: maxillaMaxilla
The maxilla is a fusion of two bones along the palatal fissure that form the upper jaw. This is similar to the mandible , which is also a fusion of two halves at the mental symphysis. Sometimes The maxilla (plural: maxillae) is a fusion of two bones along the palatal fissure that form the upper...
ry hypoplasia
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
(underdevelopment of the upper jaw
Jaw
The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term jaws is also broadly applied to the whole of the structures constituting the vault of the mouth and serving to open and close it and is part of the body plan of...
bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
), a small mandible (lower jaw bone) and receding chin
Chin
In the human anatomy, the chin is the lowermost part of the face.It is formed by the lower front of the mandible.People show a wide variety of chin structures. See Cleft chin....
, a high-arched palate
Palate
The palate is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but, in most other tetrapods, the oral and nasal cavities are not truly separate. The palate is divided into two parts, the anterior...
(the roof of the mouth), with crowding and misalignment of the upper teeth; macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
(enlarged skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...
) with a prominent forehead
Forehead
For the Arsenal striker see GervinhoIn human anatomy, the forehead is the fore part of the head. It is, formally, an area of the head bounded by three features, two of the skull and one of the scalp. The top of the forehead is marked by the hairline, the edge of the area where hair on the scalp...
, hypernasal speech
Speech
Speech is the human faculty of speaking.It may also refer to:* Public speaking, the process of speaking to a group of people* Manner of articulation, how the body parts involved in making speech are manipulated...
(voice
Human voice
The human voice consists of sound made by a human being using the vocal folds for talking, singing, laughing, crying, screaming, etc. Its frequency ranges from about 60 to 7000 Hz. The human voice is specifically that part of human sound production in which the vocal folds are the primary...
), a long nose
Human nose
The visible part of the human nose is the protruding part of the face that bears the nostrils. The shape of the nose is determined by the ethmoid bone and the nasal septum, which consists mostly of cartilage and which separates the nostrils...
with a high, narrow nasal bridge
Nasal bridge
The nasal bridge is the name given to the upper, bony part of the nose, overlying the nasal bones.A lower or higher than average nasal bridge can be a sign of various genetic disorders, such as fetal alcohol syndrome. A flat nasal bridge can be a sign of Down syndrome, Fragile X syndrome, and Fetal...
; a deep, short philtrum
Philtrum
The philtrum , is a medial cleft common to many mammals, extending from the nose to the upper lip, and, together with a glandular rhinarium and slit-like nostrils, is believed to constitute the primitive condition for mammals in general...
(the indentation in the upper lip, beneath the nose), low-set ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
s with some apparent retroversion
Anteversion
Anteversion and retroversion are complementary anatomical terms of location, describing the degree to which an anatomical structure is rotated forwards or backwards respectively, relative to some datum position.More specifically, neck anteversion is a neck tilted further forward than normal.A...
, hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
(decreased muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
), pectus excavatum
Pectus excavatum
Pectus excavatum is the most common congenital deformity of the anterior wall of the chest, in which several ribs and the sternum grow abnormally. This produces a caved-in or sunken appearance of the chest...
(a malformity of the chest
Chest
The chest is a part of the anatomy of humans and various other animals. It is sometimes referred to as the thorax or the bosom.-Chest anatomy - Humans and other hominids:...
), slightly enlarged to normal testicular
Testicle
The testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...
size in males, and seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s.
Hypernasal speech, or
Velopharyngeal inadequacy
Velopharyngeal inadequacy is a malfunction of a velopharyngeal mechanism.The velopharyngeal mechanism is responsible for directing the transmission of sound energy and air pressure in both the oral cavity and the nasal cavity. When this mechanism is impaired in some way, the valve does not fully...
, a sometimes congenital
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
aberration in which the velopharyngeal sphincter
Sphincter
A sphincter is an anatomical structure, or a circular muscle, that normally maintains constriction of a natural body passage or orifice and which relaxes as required by normal physiological functioning...
allows too much air into the nasal cavity
Nasal cavity
The nasal cavity is a large air filled space above and behind the nose in the middle of the face.- Function :The nasal cavity conditions the air to be received by the other areas of the respiratory tract...
during speech. In LFS, hypernasality may also be caused by failure of the soft palate
Soft palate
The soft palate is the soft tissue constituting the back of the roof of the mouth. The soft palate is distinguished from the hard palate at the front of the mouth in that it does not contain bone....
and uvula to reach the back wall of the pharynx
Pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...
(the interior cavity of the throat
Throat
In vertebrate anatomy, the throat is the anterior part of the neck, in front of the vertebral column. It consists of the pharynx and larynx...
where swallowing
Swallowing
Swallowing, known scientifically as deglutition, is the process in the human or animal body that makes something pass from the mouth, to the pharynx, and into the esophagus, while shutting the epiglottis. If this fails and the object goes through the trachea, then choking or pulmonary aspiration...
generally occurs) during speech, a condition that can be associated with a submucosa
Submucosa
In the gastrointestinal tract, the submucosa is the layer of dense irregular connective tissue or loose connective tissue that supports the mucosa, as well as joins the mucosa to the bulk of underlying smooth muscle .-Contents:Blood vessels, lymphatic vessels, and nerves will run through...
l cleft palate.
Cardiovascular abnormalities
A number of features involving the heartHeart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
have been noted in several LFS cases, the most significant being dilation of the aortic root, a section of the ascending aorta
Ascending aorta
The ascending aorta is a portion of the aorta commencing at the upper part of the base of the left ventricle, on a level with the lower border of the third costal cartilage behind the left half of the sternum; it passes obliquely upward, forward, and to the right, in the direction of the heart’s...
. Aortic root dilation (enlargement) is associated with a greatly increased risk of dissection
Aortic dissection
Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta and force the layers apart. The dissection typically extends anterograde, but can extend retrograde from the site of the intimal tear. Aortic dissection is a medical...
of the aortic
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
wall, resulting in aortic aneurysm
Aortic aneurysm
An aortic aneurysm is a general term for any swelling of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location...
. As this presents a possible life-threatening consequence of LFS, routine cardiac
Cardiology
Cardiology is a medical specialty dealing with disorders of the heart . The field includes diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology...
evaluation methods such as echocardiogram are implemented when the disorder is first diagnosed, along with MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
scans of the brain to screen for suspected agenesis of the corpus callosum. Additional effects on the heart that have been reported with LFS are ventricular
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
and atrial septal defect
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
.
Cause
A missense mutationMissense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
in the MED12
MED12
Mediator of RNA polymerase II transcription, subunit 12 homolog , also known as MED12, is a human gene found on the X chromosome...
gene, located on the human X chromosome
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
, has been established as the cause of LFS. Missense mutations are genetic point mutation
Point mutation
A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA. Often the term point mutation also includes insertions or deletions of a single base pair...
s in which an amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
codon that does not belong in the nucleotide sequence of a particular protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
is erroneously substituted for an amino acid that is supposed to be included in the sequence, at a specific location. The missense mutation in the MED12 gene, that causes LFS, is identified as p.N1007S. This indicates that the amino acid asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
, normally located at position 1007 along the MED12 sequence, has been mistakenly replaced by serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
. This mutation in MED12 causes incorrect expression and activity of the protein it encodes, resulting in the disorder.
Pathophysiology
Mediator (coactivator)
Mediator is a multiprotein complex that functions as a transcriptional coactivator. It was discovered by Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry...
, which regulates RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
during mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
.
The Mediator complex is required for polymerase II transcription and acts as a bridge between the polymerase II enzyme and different gene-specific transcription factors. Mediator can contain up to 30 subunits, but some of the subunits are only required for regulation of transcription in particular tissues or cells. Currently, the exact mechanism by which dysfunction of MED12 results in LFS and its associated neuropsychopathic and physical characteristics is unclear. Marfanoid habitus, a highly arched palate and several other features of LFS can be found with Marfan syndrome, a connective tissue disorder. The finding of aortic root dilation in both disorders suggests that a mutation in an unspecified connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
regulating gene may contribute to the etiology of LFS.
A number of interesting experimental results have been obtained by studying MED12 mutations in the zebrafish, an animal model
Animal model
An animal model is a living, non-human animal used during the research and investigation of human disease, for the purpose of better understanding the disease without the added risk of causing harm to an actual human being during the process...
representing vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s. In zebrafish, a mutation in MED12 was found to be responsible for the mutant motionless (mot). Zebrafish with the mot mutation have neuronal and cardiovascular defects, although not all types of neurons are affected. Introduction of human MED12 mRNA into the zebrafish restores normal development. MED12 is also a critical coactivator
Coactivator (genetics)
A coactivator is a protein that increases gene expression by binding to an activator which contains a DNA binding domain. The coactivator is unable to bind DNA by itself....
for the gene SOX9
SOX9
Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.- Function :SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins...
, which is involved in the developmental regulation of neurons, cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
. In the zebrafish, MED12 defects cause maldevelopment of vertebrate embryonic structures such as the neural crest
Neural crest
Neural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....
, which would alter function of the autonomic
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
and peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
s; and they also cause malformations of cell type
Cell type
A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...
s serving as precursors to cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
, such as osteocyte
Osteocyte
An osteocyte, a star-shaped cell, is the most abundant cell found in compact bone. Cells contain a nucleus and a thin ring of cytoplasm. When osteoblasts become trapped in the matrix they secrete, they become osteocytes...
s. Some features found in LFS, like agenesis of the corpus callosum and cartilage-related craniofacial anomalies, are similar to defects found in zebrafish with MED12 and associated mutations.
Genetics
Lujan–Fryns syndrome is inherited in an X-linked dominantX-linked dominant
X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome. As an inheritance pattern, it is less common than the X-linked recessive type...
manner. This means the defective gene responsible for the disorder (MED12) is located on the X chromosome, and only one copy of the defective gene is sufficient to cause the disorder when inherited from a parent who has the disorder. Males are normally hemizygous for the X chromosome, having only one copy. As a result, X-linked dominant disorders usually show higher expressivity
Expressivity
Expressivity is a term used in genetics to refer to variations in a phenotype among individuals carrying a particular genotype. The term can be used to characterize qualitatively or quantitatively the extent of phenotypic variation given a particular genotype. The term is analogous to the...
in males than females. This phenomenon is thought to occur with LFS.
As the X chromosome is one of the sex chromosomes (the other being the Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
), X-linked
inheritance is determined by the gender
Gender
Gender is a range of characteristics used to distinguish between males and females, particularly in the cases of men and women and the masculine and feminine attributes assigned to them. Depending on the context, the discriminating characteristics vary from sex to social role to gender identity...
of the parent carrying a specific gene and can often seem complex. This is because, typically, female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
s have two copies of the X-chromosome, while male
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
s have only one copy. The difference between dominant and recessive inheritance patterns also plays a role in determining the chances of a child inheriting an X-linked disorder from their parentage.
In LFS, X-linked dominant inheritance was suspected, as boy and girl siblings in one family both exhibited the disorder. A scenario such as this would also be possible with X-linked recessive
X-linked recessive
X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
inheritance, but in this particular case report, the girl was believed to be a manifesting heterozygote., carrying one copy of the mutated gene.
Sporadic cases of LFS, where the disorder is present in an individual with no prior family history of it, have also been reported in a small number of affected males.
Similarities to other genetic diseases
An individual exhibiting mental retardation and other symptoms similar to LFS was found to have a terminal deletion of the subtelomeric regionSubtelomere
Subtelomeres are segments of DNA "sub-" or "below" telomeric caps. Telomeres are specialized protein-DNA constructs present at the ends of eukaryotic chromosomes, which prevent them from degradation and end-to-end chromosomal fusion...
in the short arm
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
of chromosome 5. Deletion of this area of chromosome 5 is associated with mental retardation, psychotic behavior, autism, macrocephaly and hypernasal-like speech, as well as the disorder Cri du chat syndrome. Fryns (2006) suggests a detailed examination of chromosome 5 with FISH
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
should be performed as part of the differential diagnosis of LFS.
Mutations in the UPF3B
UPF3B
Regulator of nonsense transcripts 3B is a protein that in humans is encoded by the UPF3B gene.-Interactions:UPF3B has been shown to interact with UPF2 and UPF1.-Further reading:...
gene, also found on the X chromosome, are another cause of X-linked mental retardation. UPF3B is part of the nonsense-mediated mRNA decay
Nonsense mediated decay
Nonsense-mediated decay is a cellular mechanism of mRNA surveillance that functions to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. Following transcription, precursor mRNA undergoes an assemblage of ribonucleoprotein components followed by regulatory...
(NMD) complex, which performs mRNA surveillance
MRNA surveillance
mRNA surveillance mechanisms are pathways utilized by organisms to ensure fidelity and quality of messenger RNA molecules. There are a number of surveillance mechanisms present within cells...
, detecting mRNA sequences that have been erroneously truncated (shortened) by the presence of nonsense mutation
Nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
s. Mutations in UPF3B alter and prevent normal function of the NMD pathway, resulting in translation and expression of truncated mRNA sequences into malfunctioning proteins that can be associated with developmental errors and mental retardation. Individuals from two families diagnosed with LFS and one family with FGS were found to have mutations in UPF3B, confirming that the clinical presentations of the different mutations can overlap.
Diagnosis
Although LFS is usually suspected when mental retardation and marfanoid habitus are observed together in a patient, the diagnosis of LFS can be confirmed by the presence of the p.N1007S missense mutation in the MED12 gene.Differential diagnosis
In the differential diagnosisDifferential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...
of LFS, another disorder that exhibits some features and symptoms of LFS and is also associated with a missense mutation of MED12 is Opitz-Kaveggia syndrome
FG syndrome
FG syndrome is a rare genetic syndrome linked to the X chromosome and causing physical anomalies and developmental delays...
(FGS). Common features shared by both LFS and FGS include X-linked mental retardation, hyperactivity, macrocephaly, corpus callosum agenesis and hypotonia. Notable features of FGS that have not been reported with LFS include excessive talkativness, consistent strength in socialization skills, imperforate anus
Imperforate anus
An imperforate anus or anal atresia is a birth defect in which the rectum is malformed. Its cause is unknown.-Features:There are several forms of imperforate anus:* A low lesion, in which the colon remains close to the skin...
(occlusion of the anus
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
) and ocular hypertelorism
Hypertelorism
Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits . In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal...
(extremely wide-set eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
s).
Whereas LFS is associated with missense mutation p.N1007S, FGS is associated with missense mutation p.R961W. As both disorders originate from an identical type of mutation in the same gene, while exhibiting similar, yet distinct characteristics; LFS and FGS are considered to be allelic
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
. In the context of MED12, this suggests that the phenotype of each disorder is related to the way in which their respective mutations alter the MED12 sequence and its function.
Treatment
While there is no specific treatment for the underlying genetic cause of LFS; corrective procedures, preventive intervention measures and therapies may be considered in the treatment and management of the many craniofacial, orthopedic and psychiatric problems associated with the disorder. More pressing issues such as cardiac involvement or epileptic seizures should be routinely examined and monitored. Close attention and specialized follow-up care, including neuropshycological evaluation methods and therapies, and special education, should be given to diagnose and prevent psychiatric disorders and related behavioral problems such as psychosis and outbursts of aggression.Epidemiology
Lujan–Fryns syndrome is a rare X-linked dominant syndrome, and is therefore more common in males than females. Its prevalence within the general population has not yet been determined.History
Lujan–Fryns syndrome is named after physicianPhysician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s J. Enrique Lujan and Jean-Pierre Fryns. The initial observation of suspected X-linked mental retardation with Marfanoid features and craniofacial effects such as a high-arched palate
Palate
The palate is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but, in most other tetrapods, the oral and nasal cavities are not truly separate. The palate is divided into two parts, the anterior...
was described by Lujan et al. in 1984. In the report, four affected male members of a large kindred
Kinship
Kinship is a relationship between any entities that share a genealogical origin, through either biological, cultural, or historical descent. And descent groups, lineages, etc. are treated in their own subsections....
(consanguinous
Consanguinity
Consanguinity refers to the property of being from the same kinship as another person. In that respect, consanguinity is the quality of being descended from the same ancestor as another person...
family) were noted. Additional investigations of combined X-linked mental retardation and Marfanoid habitus in other families, including two brothers, were reported by Fryns et al., beginning in 1987. The disorder soon became known as Lujan–Fryns syndrome.
See also
- Fragile X syndromeFragile X syndromeFragile X syndrome , Martin–Bell syndrome, or Escalante's syndrome , is a genetic syndrome that is the most commonly known single-gene cause of autism and the most common inherited cause of intellectual disability...
- Aarskog syndrome
- Coffin–Lowry syndrome
- FG syndromeFG syndromeFG syndrome is a rare genetic syndrome linked to the X chromosome and causing physical anomalies and developmental delays...