A 5-year-old boy presents to the physician's office with coa

[Hijeck]

A 5-year-old boy presents to the physician's office with coarse facies, short stature, stiffening of the joints, and mental retardation. His parents, a 10-year-old sister, and an 8-year-old brother all appear unaffected. The patient's mother is pregnant. She had a brother who died at 15 years of age with similar findings that seemed to worsen with age. She also has a nephew (her sister's son) who exhibits similar features. Based on the probable mode of inheritance, which of the following is the risk that her fetus is affected?
A. 100%
B. 67%
C. 50%
D. 25%
E. Virtually 0

[Hijeck]

25%

The fact that the mother of the affected child has an affected brother and an affected nephew through her sister suggests X-linked recessive inheritance. This is made more likely because the symptoms suggest a mucopolysaccharidosis (storage of glycosaminoglycans) . When evaluating the possibility of an X-linked disorder, it is important to remember the pattern of inheritance of the X chromosome. Females have two X chromosomes, which are passed along in a random fashion. They pass any given X chromosome to 50% of their sons and 50% of their daughters. For an X-linked recessive condition, those daughters who inherit the affected allele are heterozygous carriers of the disorder but are not affected (in practice, some female carriers show mild expression). Since males have only one X chromosome, those who inherit the affected allele are affected with the disorder. Given X-linked recessive inheritance, the mother must have the abnormal allele on one of her X chromosomes (she is an obligate carrier) in order for her son and brother to be affected. The fetus thus has a ½ chance of being a boy and a ½ chance of being affected if male, resulting in a 1/4 (25%) overall risk of being affected.