Polycythemia at birth (hematocrit levels >70%) is common and may require treatment. Some infants with DS showa leukemoid reaction, with markedly elevated white blood cellcounts. Although this resembles congenital leukemia, it is a self-limited condition, resolving on its own over the first monthof life. Nonetheless, children with DS also have an increased risk of leukemia, with a 10to 20-fold increase in risk compared with individuals without DS. In children with DS youngerthan 2 year of age, the type is generally acute megakaryoblasticleukemia; in individuals older than 3 years of age, the types ofleukemia are similar to those of other children, with acute lymphoblastic leukemia being the predominant type.
Children with DS are more susceptible to infection, more likely to develop cataracts, and approximately 10% have atlantoaxial instability, an increased distance between the first and second cervical vertebrae that may predispose to spinal cord injury. Many individuals older than 35 years of age develop Alzheimer-like features.
The recurrence risk for parents who have had a child with DS depends on the child’s cytogenetic findings. If the child has trisomy 21, the empiric recurrence risk is 1% (added to the age-specific risk for women up to 40 years of age; after 40, the age-specific risk alone is used for subsequent pregnancies). If the child has a robertsonian translocation, chromosomal analysis of both parents must be performed. In approximately 65% of cases, the translocation is found to have arisen de novo (i.e., spontaneously, with both parents having normal karyotypes), and in 35% of cases, one parent has a balanced translocation. The recurrence risk depends on which parent is the carrier: if the mother is the carrier, the risk is 10% to 15%; if the father is the carrier, the recurrence risk is 2% to 5%.
Trisomy 18 (47,XX,+18 or 47,XY,+18) is the second most common autosomal trisomy, occurring in approximately 1 in 7500 live births. More than 95% of conceptuses with trisomy 18 are spontaneously aborted in the first trimester. Trisomy 18 is usually lethal; fewer than 10% of affected infants survive until their first birthday. Most infants with trisomy 18 are small for gestational age. Clinical features include hypertonia, prominent occiput, micrognathia, low-set and malformed ears, short
Head and face Scalp defects (e.g., cutis aplasia) Microphthalmia, corneal abnormalities Cleft lip and palate in 60%–80% of cases Microcephaly Sloping forehead Holoprosencephaly (arrhinencephaly) Capillary hemangiomas Deafness Small and premature appearance Tight palpebral fissures Narrow nose and hypoplastic nasal alae Narrow bifrontal diameter Prominent occiput Micrognathia Cleft lip or palate
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Occurring in 1 in 500 male births, KS is the most commongenetic cause of hypogonadism and infertility in men. It is causedby the presence of an extra X chromosome (47,XXY) (see Chapter 174). The extra X chromosome arises from a nondisjunctionin either the sperm or the egg. About 15% of boys with featuresof KS are found to be mosaic, with 46,XY/47,XXY mosaicismbeing the most common. Before puberty, boys with KS are phenotypically indistinguishable from the rest of the population.