A 12-year-old boy with mild intellectual disability is brought to the office by his adoptive parents for a routine physical examination. The parents say that the boy is adjusting well to a new school that has increased resources for children with learning disabilities. The patient was adopted as an infant and the birth family's history is unknown. His immunizations are up to date, and he has no allergies. Review of the patient's medical records is notable for cytogenetic studies that showed a small gap near the tip of the long arm of the X chromosome. Which of the following findings are likely to be present on this patient's physical examination?

Question

A 12-year-old boy with mild intellectual disability is brought to the office by his adoptive parents for a routine physical examination.  The parents say that the boy is adjusting well to a new school that has increased resources for children with learning disabilities.  The patient was adopted as an infant and the birth family's history is unknown.  His immunizations are up to date, and he has no allergies.  Review of the patient's medical records is notable for cytogenetic studies that showed a small gap near the tip of the long arm of the X chromosome.  Which of the following findings are likely to be present on this patient's physical examination?

Quizplus · Accepted Answer

11ec160b_3782_c100_9249_dba5e3b89d9b_MD0001_00 Fragile X syndrome, an X-linked disorder, is the most common inherited cause of intellectual disability. The defect is an unstable expansion of trinucleotide repeats (CGG) in the fragile X mental retardation 1 (FMR1) gene, located on the long arm of the X chromosome. When the cells of affected individuals are cultured in folate-deficient medium, the area of increased repeats does not stain and appears "broken," hence the name "fragile X." Cytogenetic studies (chromosomal analysis) typically show a small gap near the tip of the long arm of the X chromosome. The earliest manifestations of fragile X syndrome involve developmental delay, including delayed attainment of motor and language milestones. Mild to moderate intellectual disability is common. Classic physical features in fragile X syndrome include macrocephaly, a long narrow face, and a prominent forehead, jaw, chin, and ears. Macroorchidism (testicular enlargement) is also a key finding. All examination findings tend to be subtle during infancy and become most noticeable after puberty. (Choice A) Cardinal features of Marfan syndrome are lens dislocation (ectopia lentis) and aortic root dilation. Other common abnormalities include arachnodactyly, scoliosis, and mitral valve prolapse. Cognition and chromosomal studies are typically normal in these patients. (Choice C) Down syndrome is the most common genetic cause of intellectual disability. Classic findings include short neck, low-set ears, epicanthic folds, and slanted palpebral fissures. Cytogenetic studies usually show a karyotype with 47 chromosomes, including 3 copies of chromosome 21. (Choice D) Fetal alcohol syndrome is characterized by facial dysmorphisms (short palpebral fissures, indistinct philtrum, thin vermillion border), poor growth, and neurobehavioral problems. (Choice E) Klinefelter syndrome (47,XXY) presents with tall stature, gynecomastia, and small, firm testes. Decreased testosterone secretion by fibrotic testes causes oligospermia and infertility. Educational objective: Fragile X syndrome, an X-linked disorder, is the most common cause of inherited intellectual disability. The pathogenesis involves an unstable expansion of trinucleotide repeats (CGG) in the fragile X mental retardation 1 (FMR1) gene. Key physical findings include dysmorphic facial features (eg, large jaw, protruding ears, long face) and macroorchidism. __________ References: Fragile X syndrome: a review of associated medical problems. (http://www.ncbi.nlm.nih.gov/pubmed/25287458) Health supervision for children with fragile X syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/21518720)

A 12-Year-Old Boy with Mild Intellectual Disability Is Brought to the Office