A 15-year-old, previously healthy boy is brought to the office due to progressive muscle weakness. Over the past 2 months, the patient has had increasing difficulty making facial expressions, including smiling and frowning. He has also had difficulty swallowing but has no pain. The patient takes no medications, and vaccinations are up to date. He was adopted as an infant, and his biological family history is unknown. Physical examination shows ptosis, temporal wasting, thin cheeks, and emaciated extremities. Delayed relaxation is noted on contraction of the thenar and hypothenar muscles, which also appear atrophied. Deep tendon reflexes are normal and Babinski sign is absent. Testicular volume is small for age. What is the most likely mode of genetic transmission of this patient's condition?

Question

A 15-year-old, previously healthy boy is brought to the office due to progressive muscle weakness.  Over the past 2 months, the patient has had increasing difficulty making facial expressions, including smiling and frowning.  He has also had difficulty swallowing but has no pain.  The patient takes no medications, and vaccinations are up to date.  He was adopted as an infant, and his biological family history is unknown.  Physical examination shows ptosis, temporal wasting, thin cheeks, and emaciated extremities.  Delayed relaxation is noted on contraction of the thenar and hypothenar muscles, which also appear atrophied.  Deep tendon reflexes are normal and Babinski sign is absent.  Testicular volume is small for age.  What is the most likely mode of genetic transmission of this patient's condition?

Quizplus · Accepted Answer

11ec25c8_d5b7_c53f_bc81_4f8184f76f42_MD0003_00 This patient has classic myotonic dystrophy type 1, the most common adolescent- and adult-onset muscular dystrophy. An autosomal dominant trinucleotide (CTG) repeat expansion on the dystrophia myotonica protein kinase (DMPK) gene causes myotonia with progressive weakness of skeletal, smooth, and cardiac muscles. Disease onset and severity vary based on the length of CTG repeats, with less common but more severe phenotypes presenting in infancy or early childhood. Myotonia (delayed muscle relaxation) is most notable when an individual is unable to release the hand after a handshake (grip myotonia), as seen in this patient. Skeletal muscle weakness is prominent in the face and distal extremities (eg, forearms, hands, ankle flexors). Subsequent muscle wasting leads to the classic appearance of ptosis, temporal wasting, and limb muscle atrophy. Another feature is dysphagia (due to smooth muscle involvement), which significantly increases the risk of aspiration pneumonia. Cardiac muscle involvement can lead to conduction anomalies and arrhythmias. Other manifestations include cataracts, testicular atrophy/infertility, frontal baldness, and insulin resistance. Genetic testing confirms the diagnosis, and treatment is symptomatic care. Life expectancy is typically reduced (death at age 45-55) due to cardiac or respiratory failure. (Choice B) Congenital muscular dystrophies and some types of limb-girdle muscular dystrophies are inherited in an autosomal recessive manner. Congenital muscular dystrophies present with weakness and hypotonia in the first 2 years of life, and limb-girdle muscular dystrophies are characterized by shoulder and pelvic muscle weakness, with rare involvement of the facial muscles. (Choice C) Duchenne and Becker muscular dystrophies are usually X-linked recessive myopathies, although some cases are due to sporadic de novo mutations. Both present with progressive, proximal weakness of the lower extremities; myotonia and testicular atrophy are not seen. (Choice D) Mitochondrial diseases cause a varying degree of myopathy, which presents with fatigue, myalgia, and exercise intolerance, symptoms not seen in this patient. Myotonia is not seen with mitochondrial myopathies. (Choice E) Fragile X syndrome is an X-linked dominant disorder characterized by macroorchidism, not testicular atrophy. In addition, boys with fragile X syndrome can have low muscle tone but not grip myotonia. There are no X-linked dominant muscular dystrophies. Educational objective: Myotonic dystrophy is an autosomal dominant disorder that presents in adolescence or early adulthood with grip myotonia (delayed muscle relaxation), progressive weakness (eg, facial and hand muscles), dysphagia, and cardiac conduction anomalies. Testicular atrophy/infertility can also occur. References: The myotonic dystrophies: molecular, clinical, and therapeutic challenges. (http://www.ncbi.nlm.nih.gov/pubmed/22995693)

A 15-Year-Old, Previously Healthy Boy Is Brought to the Office