Infants with trisomy 13 have numerous malformations (seeTable 49-1). These infants are small for gestational age and microcephalic. Midline facial defects such as cyclopia (singleorbit), cebocephaly (single nostril), and cleft lip and palate arecommon, as are midline central nervous system anomalies, suchas alobar holoprosencephaly. The forehead is generally sloping,ears are often small and malformed, and microphthalmia oranophthalmia may occur. Postaxial polydactyly of the hands iscommon, as is clubfeet or rocker-bottom feet. Hypospadias andcryptorchidism are common in boys, whereas girls generallyhave hypoplasia of the labia minora. Most infants with trisomy13 also have congenital heart disease. Many infants with thiscondition have a punched-out scalp lesion over the occiputcalled aplasia cutis congenita; when seen in conjunction with polydactyly and some or all of the facial findings, this findingis essentially pathognomonic for the diagnosis of trisomy 13.
and feet. Internal malformations may include congenital heartdefect (in 45%, coarctation of the aorta is the most commonanomaly, followed by bicuspid aortic valve; later in life, poststenotic aortic dilation with aneurysm may develop). Renalanomalies, including horseshoe kidney, are seen in more than50% of patients. Short stature is a cardinal feature of this condition, and acquired hypothyroidism is estimated to occur fivetimes more frequently in women with TS than in the generalpopulation.
The presence of streak gonads (gonadal dysgenesis) instead of well-developed ovaries leads to estrogen deficiency, which prevents these women from developing secondary sexual characteristics and results in amenorrhea. Although 10% of women with TS may have normal pubertal development and are even fertile, most affected women require estrogen replacement to complete secondary sexual development.
Infertility in these women is not corrected by estrogen replacement. Assisted reproductive technology using donor ova hasallowed women with TS to bear children. During pregnancy,these women must be followed carefully, because poststenoticdilatation of the aorta, leading to dissecting aneurysm, may occur.
Many girls with TS escape detection during the newborn period because phenotypic features are subtle. About 33% of children with TS are diagnosed in the newborn period because of the presence of heart disease and physical features; another 33% are diagnosed in childhood, often during a workup for short stature (and receive growth hormone therapy); the final 33% are diagnosed during adolescence when they fail to develop secondary sexual characteristics.
The karyotypic spectrum in girls with TS is wide. Only 50% have a 45,X karyotype; 15% have an isochromosome Xq [46,X,i(Xq)], in which one X chromosome is represented by two copies of the long arm (leading to a trisomy of Xq and a monosomy of Xp); and approximately 25% are mosaic (45,X/46,XX or 45,X/46,XY). Deletions involving the short (p) arm of the X chromosome (Xp22) produce short stature and congenital malformations, whereas deletions of the long arm (Xq) cause gonadal dysgenesis.
Although monosomy X is caused by nondisjunction, TS is not associated with advanced maternal age. Rather, it is believed that the 45,X karyotype results from a loss of either an X or a Y chromosome after conception; that is, it is a postconceptual mitotic (rather than meiotic) nondisjunctional event.