Other X Chromosome Abnormalities
There are a number of other chromosome abnormalities with regard to the X chromosome.
Triple X syndrome or 47,XXX syndrome
This syndrome occurs 1 in 1000 births, so that in the US five to ten triple X syndrome girls are born every day. The are growing a few centimeters taller than their female siblings, but usually weigh less. The extra X chromosome came from a random error in cell division in the formation of the reproductive cells (ovum or sperm), which is called “non disjunction”. Some individuals have a mix of cells with 46,XX (normal) and 47,XXX cells; they are said to be 46,XX/47,XXX mosaics. Advanced maternal age (age above 40) plays a role in causing a non disjunction in the mother and most cases are maternally derived.
Girls with triple X syndrome may be noticed first when they display a learning disability. They may have delayed speech and language skills. The have normal sexual development, but often have an early onset of menstruation. They tend to have more menstrual irregularities. Most triple X syndrome women can conceive children normally and they often do not get diagnosed during prenatal check-ups as genetic tests are not routinely done. However, a minority may present at infertility clinics for a work-up. If they have an amniocentesis done, they may be diagnosed by chance. Many professionals do not consider this to be an abnormality, just a variation of normal. The only reason it is of value to know about triple X syndrome as parents is that a learning disability can be detected earlier and thus get remedied early with better long-term results.
48,XXXX and 49,XXXXX syndromes
These women with more than 3 x chromosomes do exist. However, if there are more than 3 X chromosome, the degree of mental retardation is getting very severe. Also the amount of associated congenital abnormalities in various organ systems increases markedly.
48,XXXX (or Tetrasomy X) patients have a characteristic face with epicanthal folds, a small mouth and a cleft palate or high arched palate. Teeth can be missing or be delayed with enamel defects. There is moderate mental retardation with an IQ of 60 to 70. Developmental delays are common with walking occurring at only 1 ½ to 4 years. Puberty is normal in half the cases, the others have significant delays or fail to develop secondary sexual characteristics. Many XXXX syndrome girls have menstrual irregularities and premature menopause, often in their teens. Maldeveloped eyes (microphthalmos) and optic nerve hypoplasia can cause severe visual loss or blindness. Otherwise myopia and nystagmus are common. Severe heart and kidney abnormalities are common. Seizures without documentable brain abnormalities also are found not infrequently. Ear abnormalities affecting hearing are common as a re recurrent ear infections. The prognosis of tetrasomy girls is relatively good, if mental retardation is not too severe. Many will need estrogen therapy during puberty to help initiate breast development. Otherwise speech therapy, learning assistance and physical therapy is often required.
XXXXX syndrome (or Pentasomy X) has microcephaly and micrognathia (small head and small jaw). The neck is webbed much like Turner syndrome. There is scoliosis and hypotonia (weak muscles). Toes are overlapping. The mouth often shows a cleft palate, a highly arched palate and dental abnormalities. They often have severe cardiac abnormalities and kidney defects. There is retarded growth and severe mental retardation with an IQ of only 45 to 55.
Fragile X syndrome
This is an inherited condition that is X chromosome linked, but is recessively inherited. In other words, there can be an apparently healthy female that is a carrier and she can have a son who gets the disease. This is a syndrome that causes mental retardation, a number of malformations in the head, heart, musculoskeletal system and also causes autism. Here is an image of a child with fragile X syndrome. It occurs with a frequency of 1 in 3,600 boys and a frequency of about 1 in 5,000 girls. This image shows the genetic transmission of fragile X syndrome: For more detailed information see Ref.2 below.
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