XXXX syndrome
Encyclopedia
XXXX syndrome is a rare chromosomal disorder
caused by the presence of four X chromosome
s instead of two X chromosomes. This condition occurs only in females, as there are no Y chromosomes present. Tetrasomy X was first described in 1961, and since then approximately 100 cases have been reported worldwide. Approximately 60 females have been described in medical literature with this condition.
, meaning it arises from a defect in meiosis
. This can occur when homologous X chromosomes fail to separate in the formation of the egg or sperm. Tetrasomy X is usually suspected based on symptoms present in the individual and is confirmed via karyotyping
, which reveals the extra X chromosomes.
s, flat nasal bridges, upslanting palpebral fissure
s, midface hypoplasia
, small mouths, cleft or high arched palates, delayed or absent teeth, or enamel defects. The majority have also been reported as being longer and taller. Many also show joint and muscle tone abnormalities, including hypotonia
and joint looseness in the hips. Skeletal problems may also be present, including abnormal curvatures of the spine. An informal study conducted by Tetrasomy & Pentasomy X Syndrome Information and Support found that 10% of girls had joint laxity in the hips and 20% had joint limitations in a sample size of 20 tetrasomy and pentasomy patients.
Developmentally, tetrasomy X patients frequently show mild delays in the areas of speech development and articulation, language expression and understanding, and reading skills. Delays in motor development are also present, with walking ages ranging from 16 months to 4.5 years. About 50% of patients undergo puberty
normally, whereas the other 50% experiences no puberty, partial puberty without secondary sexual characteristics, or complete puberty with menstrual irregularities and/or early menopause (possibly as early as the teens). Medical literature reports four tetra-X pregnancies, two healthy, one with trisomy 21, one stillborn with omphalocele
.
In terms of internal organ systems, tetrasomy X patients may have abnormal vision, hearing, circulatory systems, kidneys, or nervous systems. Disorders of the eye include myopia
, nystagmus, coloboma
, microphthalmus, or optic nerve hypoplasia
. In terms of hearing, patients are more prone to ear infections, sound blockage, or nerve abnormalities. Several cardiac defects have also been reported, including ventricular/atrial septal defects, atresia
, hypoplastic right heart syndrome
, patent ductus arteriosus
, and conotruncal or valvular cardiac defects. Tetrasomy X patients also appear to be more prone to seizure activity, although there is no documented abnormalities in brain function or structure when analyzed using an EEG
or MRI.
this kind of chromosomal arrangement is normal. In this species genetic sex differentiation works like this
Chromosome abnormalities
A chromosome anomaly, abnormality or aberration reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes. A Karyotype refers to a full set of chromosomes from an individual which can be compared to a "normal" Karyotype for the species via genetic testing. A...
caused by the presence of four 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...
s instead of two X chromosomes. This condition occurs only in females, as there are no Y chromosomes present. Tetrasomy X was first described in 1961, and since then approximately 100 cases have been reported worldwide. Approximately 60 females have been described in medical literature with this condition.
Causes and diagnosis
Tetrasomy X is a chromosomal aneuploidyAneuploidy
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate...
, meaning it arises from a defect in meiosis
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
. This can occur when homologous X chromosomes fail to separate in the formation of the egg or sperm. Tetrasomy X is usually suspected based on symptoms present in the individual and is confirmed via karyotyping
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
, which reveals the extra X chromosomes.
Symptoms
Symptoms of tetrasomy X are highly variable, ranging from relatively mild to severe. Physically, tetrasomy X patients tend to have distinctive facial features such as epicanthal foldEpicanthal fold
An epicanthic fold, epicanthal fold, or epicanthus is a skin fold of the upper eyelid, covering the inner corner of the eye....
s, flat nasal bridges, upslanting palpebral fissure
Palpebral fissure
Palpebral fissure is the anatomic name for the separation between the upper and lower eyelids. In adults, this measures about 10mm vertically and 30mm horizontally.It can be reduced in horizontal size by fetal alcohol syndrome and in Williams Syndrome...
s, midface 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...
, small mouths, cleft or high arched palates, delayed or absent teeth, or enamel defects. The majority have also been reported as being longer and taller. Many also show joint and muscle tone abnormalities, including 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...
and joint looseness in the hips. Skeletal problems may also be present, including abnormal curvatures of the spine. An informal study conducted by Tetrasomy & Pentasomy X Syndrome Information and Support found that 10% of girls had joint laxity in the hips and 20% had joint limitations in a sample size of 20 tetrasomy and pentasomy patients.
Developmentally, tetrasomy X patients frequently show mild delays in the areas of speech development and articulation, language expression and understanding, and reading skills. Delays in motor development are also present, with walking ages ranging from 16 months to 4.5 years. About 50% of patients undergo puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
normally, whereas the other 50% experiences no puberty, partial puberty without secondary sexual characteristics, or complete puberty with menstrual irregularities and/or early menopause (possibly as early as the teens). Medical literature reports four tetra-X pregnancies, two healthy, one with trisomy 21, one stillborn with omphalocele
Omphalocele
An omphalocele is a type of abdominal wall defect in which the intestines, liver, and occasionally other organs remain outside of the abdomen in a sac because of a defect in the development of the muscles of the abdominal wall.-Presentation:The sac, which is formed from an outpouching of...
.
In terms of internal organ systems, tetrasomy X patients may have abnormal vision, hearing, circulatory systems, kidneys, or nervous systems. Disorders of the eye include 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...
, nystagmus, coloboma
Coloboma
A coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid or optic disc...
, microphthalmus, or optic nerve hypoplasia
Optic nerve hypoplasia
Optic nerve hypoplasia is a medical condition arising from the underdevelopment of the optic nerve. This condition is the most common congenital optic nerve anomaly. The optic disc appears abnormally small, because not all the optic nerve axons have developed properly...
. In terms of hearing, patients are more prone to ear infections, sound blockage, or nerve abnormalities. Several cardiac defects have also been reported, including ventricular/atrial septal defects, atresia
Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.Examples of atresia include:* Imperforate anus - malformation of the opening between the rectum and anus....
, hypoplastic right heart syndrome
Hypoplastic right heart syndrome
Hypoplastic right heart syndrome is a condition where the right atrium and right ventricle are underdeveloped.It is less common than hypoplastic left heart syndrome.In some cases it can be identified prenatally.It can be associated with aortic stenosis....
, patent ductus arteriosus
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
, and conotruncal or valvular cardiac defects. Tetrasomy X patients also appear to be more prone to seizure activity, although there is no documented abnormalities in brain function or structure when analyzed using an EEG
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...
or MRI.
Treatment and prognosis
The general prognosis for girls with tetrasomy X is relatively good. Due to the variability of symptoms, some tetrasomy X girls are able to function normally, whereas others will need medical attention throughout their lives. Traditionally, treatment for tetrasomy X has been management of the symptoms and support for learning. Most girls are placed on estrogen treatment to induce breast development, arrest longitudinal growth, and stimulate bone formation to prevent osteoporosis. Speech, occupational, and physical therapy may also be needed depending on the severity of the symptoms.In other species
With the EchidnaEchidna
Echidnas , also known as spiny anteaters, belong to the family Tachyglossidae in the monotreme order of egg-laying mammals. There are four extant species, which, together with the platypus, are the only surviving members of that order and are the only extant mammals that lay eggs...
this kind of chromosomal arrangement is normal. In this species genetic sex differentiation works like this
- 63 (XXY, male)
- 64 (XXXX, female)