A 16-year-old boy with mild intellectual disability is brought to the office to be evaluated for attention deficit-hyperactivity disorder. The parents state that he has always been impulsive and inattentive and that teachers are concerned about his inattentiveness and poor grades. Review of medical records shows a history of gross motor and speech delay for which he received physical and speech therapies during childhood. On physical examination, the boy has a long and narrow face, a prominent mandible, and large testes. There is hyperlaxity of his finger and thumb joints. Which of the following is the most likely diagnosis in this patient?

Question

A 16-year-old boy with mild intellectual disability is brought to the office to be evaluated for attention deficit-hyperactivity disorder.  The parents state that he has always been impulsive and inattentive and that teachers are concerned about his inattentiveness and poor grades.  Review of medical records shows a history of gross motor and speech delay for which he received physical and speech therapies during childhood.  On physical examination, the boy has a long and narrow face, a prominent mandible, and large testes.  There is hyperlaxity of his finger and thumb joints.  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec160b_3783_f982_9249_3f9e9670fce1_MD0001_00 This patient has fragile X syndrome (FXS), the most common inherited and the second most common congenital cause of intellectual disability. FXS is an X-linked disorder caused by a loss-of-function mutation in the fragile X mental retardation 1 (FMR1) gene on the long arm of the X chromosome. Males who inherit the full mutation will manifest the features of FXS, whereas females with one abnormal X chromosome will have a milder and variable presentation. The clinical features of FXS are most apparent after puberty in males; affected individuals have a long, narrow face, a prominent forehead and chin, and large testes. Patients often have hyperlaxity of the joints in the hand. Developmental delay (speech and motor) is common in infancy, but neuropsychiatric features often present in childhood (eg, anxiety, attention deficit-hyperactivity disorder, autism spectrum disorder). (Choice A) Down syndrome, or trisomy 21, is the most common cause of congenital intellectual disability. In patients with Down syndrome mosaicism, some cells (but not all) have an extra copy of chromosome 21. These patients may have a milder presentation than those with classic Down syndrome. (Choice B) Ehlers-Danlos syndrome is a connective tissue disorder that is most commonly due to defective type V collagen production. Patients typically have skin hyperelasticity and fragility as well as joint hyperlaxity. Ehlers-Danlos syndrome is not associated with intellectual disability. (Choice D) Patients with Klinefelter syndrome (47,XXY) often have mild intellectual disability in addition to tall stature, gynecomastia, small testes (often undescended), and infertility. (Choice E) Marfan syndrome is an autosomal dominant connective tissue disorder characterized by tall stature, arachnodactyly (long and thin fingers), ectopia lentis (lens displacement), and dilation of the proximal aorta. Intellectual disability is not associated with Marfan syndrome. (Choice F) Prader-Willi syndrome is an imprinting disorder caused by a paternal deletion of part of chromosome 15. In infancy, hypotonia and hyperphagia lead to gross motor delays and obesity, respectively. Intellectual disability and behavioral problems (eg, autistic-like behaviors, obsessive compulsive features) are common. Educational objective: Fragile X syndrome is an X-linked disorder that presents with a long, narrow face, a prominent chin and forehead, and large testes. Patients often have developmental delay and neuropsychiatric findings that overlap with anxiety disorders, autism, and attention deficit-hyperactivity disorder. __________ References: Fragile X syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/25767309)

A 16-Year-Old Boy with Mild Intellectual Disability Is Brought to the Office