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NEUROSAE 2018 ANNUAL MEETING EDITION (VOLUME 10, ISSUE 3)
QUESTION 87 OF 100
A 57-year-old man presents with muscle fatigue and weakness, increasing difficulty when rising from a chair or using his arms above his head, and pain in both hips and shoulders, with the left side more affected than the right. He states he never has had much arm strength, walks with a clumsy gait, but exercises on a stationary bike twice weekly, although he has never been able “lose his gut.” History includes moderate hearing loss, sleep apnea, mild dysphagia, and an abdominal hernia repair at a surgical incision scar. Examination reveals weakness of shoulder abduction, with the left side affected more than the right, internal rotation of the left scapula, and atrophy of the left pectoralis muscle. He also has moderate weakness of the proximal muscles more than the distal muscles of the lower extremity. He has a decreased smile, affecting the left side more than the right. EMG/nerve conduction studies confirm a myopathic process. A photograph of the patient are shown. Which of the following studies should be ordered to confirm the diagnosis?
A. Sarcoglycan gene panel testing **
B. SMCHD1 gene testing
C. Muscle immunohistochemistry and electron microscopy
D. Serum anti-NT5C1a antibodies
E. GAA gene sequencing
** = Your answer
Facioscapulohumeral muscular dystrophy (FSHD) typically presents before age 20 years and is characterized by weakness of the facial muscles, the stabilizers of the scapula (scapular winging), and the foot dorsiflexors. FSHD has an autosomal dominant inheritance pattern and is likely caused by inappropriate expression of the double homeobox-containing gene DUX 4 in muscle cells, which lies in the macrosatellite repeat D4Z4 on chromosome 4q35 (normal 11-100 repeats).
FSHD1 accounts for approximately 95% of cases and is caused by shortening of the D4Z4 allele (1-10 repeats), resulting in chromatin relaxation at the D4Z4 locus and DUX4 promoter and in turn depression of DUX4. FSHD2, which accounts for approximately 5% of cases, is characterized by chromatin relaxation at D4Z4 without a D4Z4 contraction, but rather a mutation in SMCHD1 and DUX4 permissive allele. FSHD1 and FSHD2 are clinically indistinguishable.
Clinical presentation typically includes facial weakness, especially of the rhizoris muscles, with a flattened smile and inability to pucker, whistle, or suck through a straw. Patients may have ptosis but more commonly have weak eye closure. Muscle weakness is often asymmetric with rounding of the shoulders, atrophy of the pectoralis muscles, and scapular winging. Additional features include predominant involvement of the humeral and shoulder girdle muscles. Innate weakness of the abdominal muscles often is associated with a protuberant abdomen and a higher incidence of incision-related hernias due to the muscle defect. More than 50% of patients report asymmetric pain attributed to incomplete joint mobility.
* Goyal N. The genetics of inherited and acquired myopathy. Advances in Neurogenetics C28 AAN Annual Meeting 2017.