Flynn Aird syndrome
Encyclopedia
Flynn-Aird Syndrome is a rare, hereditary, neurological disease that is inherited in an autosomal dominant fashion. The syndrome involves defects in the nervous, auditory, skeletal, visual, and endocrine systems and encompasses numerous symptoms, bearing striking similarity to other known syndromes of neuroectodermal nature such as: Werner syndrome
, Cockayne syndrome
and Refsum syndrome.
The onset of Flynn-Aird Syndrome typically occurs between ten and twenty years of age, however, the earliest case was diagnosed at age seven. As the syndrome progresses, initial symptoms tend to intensify and new symptoms become apparent. Unlike related syndromes and despite the intensity of symptoms in the disease progression, Flynn-Aird syndrome does not appear to shorten life expectancy.
The disease is characterized by early-onset dementia
, ataxia
, muscle wasting, skin atrophy
, and eye abnormalities. In addition, patients have the potential of developing a number of other related symptoms such as: cataracts, retinitis pigmentosa
, myopia
(nearsightedness), dental caries
, peripheral neuropathy
(peripheral nerve damage), deafness, and cystic bone changes. This syndrome was first discovered in the early 1950s by American neurologists P. Flynn and Robert B. Aird
who analyzed one family lineage inheritance pattern of this disease.
. This is supported by the fact that the disease failed to skip generations even in the absence of intermarriages and that disease incidence was independent of sex. The current findings suggest that the cause of the disease could be narrowed down to one enzymatic defect that is involved in the development of neuroectodermal tissue, however the exact molecular mechanisms are currently unknown. The other symptoms that arise such as bone defects and diabetes may be secondary to this enzymatic defect.
and is known as bilateral nerve deafness. Another early symptom is the development of myopia (nearsightedness). In addition to bilateral nerve deafness and myopia, other symptoms that plague infected individuals early in disease progression include ataxia, muscle wasting, severe peripheral neuritic pain sometimes accompanied by elevated spinal fluid protein, and joint stiffness
.
The central nervous system
(CNS) is affected with deficits in the cerebral cortex
which indicate signs of mental retardation
even though psychological observations appear relatively normal for individuals studied. Atypical epilepsy
is also a common feature of CNS malfunctioning including aphasia
expressions, blurred vision, and numbness of the face and limbs.
In the third decade of the condition, individuals develop further visual problems including retinitis pigmentosa, and bilateral cataracts. Sufferers endure the restriction of visual fields, night blindness, and eventually severe or complete blindness
.
Individuals with this syndrome exhibit many physical deformities including skeletal, epidermal, and subcutaneous abnormalities. The skeletal problems are characterized by scoliosis and muscle weakness indicative of the kyphoscoliotic type which follow muscle wasting and peripheral neuritis (nerve inflammation). Osteoporosis
is also observed in many cases. Skin and subcutaneous atrophy is common as well as skin ulcerations due to inability of the skin to heal. One of the final manifestations of disease is baldness
.
There is no evidence that the progression of Flynn-Aird disease shortens the patient's life-span, but the terrible conditions certainly increase morbidity.
Werner syndrome
Werner syndrome is a very rare, autosomal recessive disorder characterized by the appearance of premature aging....
, Cockayne syndrome
Cockayne syndrome
Cockayne syndrome is a rare autosomal recessive, congenital disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight , and premature aging...
and Refsum syndrome.
The onset of Flynn-Aird Syndrome typically occurs between ten and twenty years of age, however, the earliest case was diagnosed at age seven. As the syndrome progresses, initial symptoms tend to intensify and new symptoms become apparent. Unlike related syndromes and despite the intensity of symptoms in the disease progression, Flynn-Aird syndrome does not appear to shorten life expectancy.
The disease is characterized by early-onset dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, muscle wasting, skin atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
, and eye abnormalities. In addition, patients have the potential of developing a number of other related symptoms such as: cataracts, retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
, myopia
Myopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...
(nearsightedness), dental caries
Dental caries
Dental caries, also known as tooth decay or a cavity, is an irreversible infection usually bacterial in origin that causes demineralization of the hard tissues and destruction of the organic matter of the tooth, usually by production of acid by hydrolysis of the food debris accumulated on the...
, peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
(peripheral nerve damage), deafness, and cystic bone changes. This syndrome was first discovered in the early 1950s by American neurologists P. Flynn and Robert B. Aird
Robert B. Aird
Robert Burns Aird , an American educator and physician, founded the department of neurology at the University of California at San Francisco...
who analyzed one family lineage inheritance pattern of this disease.
History
P.Flynn and Robert B. Aird observed this neuroectodermal syndrome after studying one family whose members suffered a number of neurological symptoms that were consistent from generation to generation. A number of the symptoms overlapped with several known neurological diseases such as Werner syndrome, Refsum syndrome, and Cockayne syndrome, which could be indicative of similar causative origins. However, it should be noted that these syndromes are recessively inherited as opposed to the dominant inheritance seen in the family studied by P. Flynn and Robert B. Aird. About 15% of family members exhibited full-blown symptoms characteristic of the disease while others showed some symptoms that overlapped with the general clinical manifestation of the syndrome.Genetics
One family of 68 individuals over 5 generations was studied and the prevalence of disease among the family members suggests that it is indicative of dominant inheritance that is not sexually linkedSex 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...
. This is supported by the fact that the disease failed to skip generations even in the absence of intermarriages and that disease incidence was independent of sex. The current findings suggest that the cause of the disease could be narrowed down to one enzymatic defect that is involved in the development of neuroectodermal tissue, however the exact molecular mechanisms are currently unknown. The other symptoms that arise such as bone defects and diabetes may be secondary to this enzymatic defect.
Pathophysiology
The exact pathophysiological mechanism of Flynn-Aird Syndrome is unknown. However, several theories are in place with regards to the nature of this disease including the presence of a genetically defective enzyme involving a neuroectodermal tissue constituent. This explanation provides evidence for the late onset of the condition, the intricate findings, the varied nature of the disorder, as well as the genetic incidence. In addition, some aspects of the condition may be linked to a suppressing (S) gene due to the fact that only a small amount of stigmata appeared while the defects were still transmitted in the family studied. A suppressing gene down regulates the phenotypic expression of another gene, especially of a mutant gene. Other abnormalities may be due to endocrine system diseases.Symptoms
Individuals with this syndrome typically develop normally until reaching the second decade of their lives but the onset of symptoms has been observed as early as age seven. The first defect observed in individuals who suffer from this condition affects the auditory systemAuditory system
The auditory system is the sensory system for the sense of hearing.- Outer ear :The folds of cartilage surrounding the ear canal are called the pinna...
and is known as bilateral nerve deafness. Another early symptom is the development of myopia (nearsightedness). In addition to bilateral nerve deafness and myopia, other symptoms that plague infected individuals early in disease progression include ataxia, muscle wasting, severe peripheral neuritic pain sometimes accompanied by elevated spinal fluid protein, and joint stiffness
Joint stiffness
Joint stiffness may be either the symptom of pain on moving a joint, the symptom of loss of range of motion or the physical sign of reduced range of motion. Doctors prefer the latter two uses but patients often use the first meaning....
.
The central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) is affected with deficits in the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
which indicate signs of 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...
even though psychological observations appear relatively normal for individuals studied. Atypical epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
is also a common feature of CNS malfunctioning including aphasia
Aphasia
Aphasia is an impairment of language ability. This class of language disorder ranges from having difficulty remembering words to being completely unable to speak, read, or write....
expressions, blurred vision, and numbness of the face and limbs.
In the third decade of the condition, individuals develop further visual problems including retinitis pigmentosa, and bilateral cataracts. Sufferers endure the restriction of visual fields, night blindness, and eventually severe or complete blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
.
Individuals with this syndrome exhibit many physical deformities including skeletal, epidermal, and subcutaneous abnormalities. The skeletal problems are characterized by scoliosis and muscle weakness indicative of the kyphoscoliotic type which follow muscle wasting and peripheral neuritis (nerve inflammation). Osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
is also observed in many cases. Skin and subcutaneous atrophy is common as well as skin ulcerations due to inability of the skin to heal. One of the final manifestations of disease is baldness
Baldness
Baldness implies partial or complete lack of hair and can be understood as part of the wider topic of "hair thinning". The degree and pattern of baldness can vary greatly, but its most common cause is male and female pattern baldness, also known as androgenic alopecia, alopecia androgenetica or...
.
There is no evidence that the progression of Flynn-Aird disease shortens the patient's life-span, but the terrible conditions certainly increase morbidity.