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Abstract Details

Facioscapulohumeral Muscular Dystrophy Type 2 due to a Novel Pathogenic Variant (c.180_183delGTGT : p.Cys61ArgfsX47) in the SMCHD1 Gene, Confirmed by Molecular Testing: A Case Report
Neuromuscular and Clinical Neurophysiology (EMG)
Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)
025
To describe a case of facioscapulohumeral muscular dystrophy type 2 (FSHD2) with a novel pathogenic variant in SMCHD1.
FSHD2 is a rare muscular dystrophy presenting with weakness predominantly in facial, shoulder girdle, and distal lower extremity muscles.  Pathogenic mutations in SMCHD1 result in hypomethylation of the D4Z4 region. This leads to DUX4 expression in the setting of a 4qA allele (another independent genetic variation), so producing the FSHD2 phenotype. Testing demonstrating hypomethylation at D4Z4 is necessary to confirm diagnosis in these cases.   
Case report.
A 61 year-old woman presented with a 9-month history of fatigue, right leg weakness and difficulty walking.  Exam demonstrated subtle orbicularis oris weakness,  and mild asymmetric weakness of shoulder abduction, internal rotation, and external rotation without clear scapular winging. Additionally, there was mild weakness of right ankle dorsiflexion and bilateral finger and thumb flexion and abduction.  Left leg strength was normal.  Mild atrophy was noted in intrinsic hand and deltoid muscles.  Reflexes were normal throughout.  Sensation was reduced to pinprick and vibration below the ankles bilaterally, but intact to proprioception and temperature.  There was difficulty with tandem gait, otherwise ambulation was normal.  A known family history of “limb girdle muscular dystrophy” was reported, affecting her father and sister. CK was mildly elevated at 421 U/L.  EMG revealed myopathic motor unit potentials in the orbicularis oris as well as proximal upper and distal lower extremities.  FSHD was suspected, but testing for D4Z4 contraction was negative.  Whole exome sequencing identified a likely pathogenic but novel variant (c.180_183delGTGT : p.Cys61ArgfsX47) in SMCHD1.  Subsequent testing confirmed hypomethylation of the D4Z4 region in the setting of a 4qA allele to secure the diagnosis of FSHD2.
This case describes a novel pathogenic variant (c.180_183delGTGT : p.Cys61ArgfsX47) in SMCHD1, responsible for a late presentation of FSHD2. 
Authors/Disclosures
Mathieu Cuchanski, DO
PRESENTER 		Dr. Cuchanski has nothing to disclose.
John A. Morren, MD, FÂ鶹´«Ã½Ó³»­ (Cleveland Clinic) Dr. Morren has received publishing royalties from a publication relating to health care.