A 38-year-old male visited our clinic for asymmetric upper extremity weakness. The patient reported that, at the age of nine, he had difficulty performing iron bar gymnastics. Since his third decade, he experienced prominent right shoulder and arm weakness, and he presented with facial asymmetry and weakness. Physical examination showed a transverse smile, positive Beevor's sign, and winged scapula (). In addition, he showed facial and bilateral arm and leg weakness with proximal dominance and asymmetricity (right side more severe than the left) on neurological examination. Serum creatinine kinase levels were mildly elevated at 224 unit/L. His mother and elder sister had similar symptoms (). We performed genetic analysis for FSHD. Southern blotting analysis by the EcoRI/BlnI digestion method using genomic DNA revealed that a fragment size of 37 kb, and the number of D4Z4 repeats was nine. Bisulfite sequencing to determine the haplotype of D4Z4 using digestion with HindIII and hybridized with 4qA probe and target sequencing analysis to screen for mutations in the SMCHD1 gene by a next-generation sequencer (Ion PGMTM) were performed for FSHD2 diagnosis. We found reduced DNA methylation ratio (16.8%), D4Z4 haplotype 4qA (homozygous), and c.1580C>T (p.T527M) SMCHD1 mutation, which was previously reported to be a pathogenic allele.\nInformed consent was obtained from the two patients regarding the reporting and publication of this case report.
Patient 1 was a 30-yr-old woman complaining of progressive limb muscle weakness. She was in good health until age 12 yr, at which time she began to have a difficulty in raising her right arm above her head. Later, she developed increasing difficulties climbing stairs. By report, her mother had similar symptoms from the age of 40. His 35-yr-old brother was not affected clinically (). The neurological examination was remarkable for moderate facial weakness; moderate (Medical Research Council [MRC] grade 3) and mild (MRC grade 4) weakness of proximal upper and lower limb muscles, respectively; humeral atrophy; anterior axillary folds; winged scapulae; waddling gait; and hypoactive deep tendon reflexes. The serum creatine kinase (CK) was 233 IU/L (normal, <270 IU/L). Other routine laboratory tests including thyroid and parathyroid function were normal. Audiogram, electrocardiogram, echocardiogram, nerve conduction studies were unremarkable. Needle electromyography showed chronic myopathic changes in the left deltoid, biceps brachii, and vastus lateralis muscles. A muscle biopsy from the right vastus lateralis revealed marked fiber size variations, increased internalized nuclei, endomyseal fibrosis and fat ingrowth, and frequent lobulated myofibers.