Spectrum of skeletal muscle channelopathies in a cohort of Inherited neuromuscular disorders

Skeletal muscle channelopathies are rare genetic neuromuscular disorders comprising periodic paralyses and non-dystrophic myotonias. Paroxysmal symptoms, near-normal clinical examination and investigations may sometimes make these disorders challenging. All clinically suspected patients with skeletal muscle channelopathy were recruited prospectively in the MRC-funded International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) cohort. All patients underwent serum electrolytes, creatine kinase, TFT, Cortisol, Autoimmune profile, urinary potassium, ECG, Echocardiography, NCS, EMG, Exercise test and whole exome sequencing. We enrolled 18 probands with suspected clinical features suggestive of skeletal muscle channelopathy in the form of myotonia and/or episodic weakness. The mean age of the patients was 23 years, with 16 males. Clinical feature as isolated myotonia was seen in 5 patients, episodic weakness in 12 patients and both in 1 patient. Among six patients having myotonia, a warm-up phenomenon was seen in 4 patients, cold phenomenon, i.e. paradoxical myotonia, in 2 patients. Positive family history was seen in 7 patients. CPK levels were > 1000 U/L in 2 patients with periodic paralysis. The clinical diagnosis of the probands was myotonia congenita (5), paramyotonia congenita (1) and Periodic paralysis (12). WES results are available in eight probands and awaited in 10 probands. Among myotonia congenita, one was solved (CLCN1 c1096G>A; c.2083G>T), and the other was unsolved. The suspected paramyotonia congenita was unsolved after WES. Among periodic paralysis, four were solved (one hyperkalemic periodic paralysis and three hypokalemic periodic paralysis - SCN4A, CACNA1S). We describe the clinical and genetic spectrum of skeletal muscle channelopathy from a cohort of inherited neuromuscular disorders in India. Skeletal muscle channelopathies are rare genetic neuromuscular disorders comprising periodic paralyses and non-dystrophic myotonias. Paroxysmal symptoms, near-normal clinical examination and investigations may sometimes make these disorders challenging. All clinically suspected patients with skeletal muscle channelopathy were recruited prospectively in the MRC-funded International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) cohort. All patients underwent serum electrolytes, creatine kinase, TFT, Cortisol, Autoimmune profile, urinary potassium, ECG, Echocardiography, NCS, EMG, Exercise test and whole exome sequencing. We enrolled 18 probands with suspected clinical features suggestive of skeletal muscle channelopathy in the form of myotonia and/or episodic weakness. The mean age of the patients was 23 years, with 16 males. Clinical feature as isolated myotonia was seen in 5 patients, episodic weakness in 12 patients and both in 1 patient. Among six patients having myotonia, a warm-up phenomenon was seen in 4 patients, cold phenomenon, i.e. paradoxical myotonia, in 2 patients. Positive family history was seen in 7 patients. CPK levels were > 1000 U/L in 2 patients with periodic paralysis. The clinical diagnosis of the probands was myotonia congenita (5), paramyotonia congenita (1) and Periodic paralysis (12). WES results are available in eight probands and awaited in 10 probands. Among myotonia congenita, one was solved (CLCN1 c1096G>A; c.2083G>T), and the other was unsolved. The suspected paramyotonia congenita was unsolved after WES. Among periodic paralysis, four were solved (one hyperkalemic periodic paralysis and three hypokalemic periodic paralysis - SCN4A, CACNA1S). We describe the clinical and genetic spectrum of skeletal muscle channelopathy from a cohort of inherited neuromuscular disorders in India.