Severe Neonatal Apnea Episodes Associated with a Nondystrophic Congenital Myotonia Caused by a Mutation in the Gene SCN4A

Case Study: A neonate showed daily episodes of apnea associated with cyanosis and stridor followed by generalized stiffness lasting no more than 20 seconds. These episodes occur only in the supine position or during feeding. The neurological examination showed moderate muscular hypotonia of the trunk and hypertrophic shoulder girdle muscles. The psychomotor development was normal.

Diagnostics: Initial cardiac, cerebral, and metabolic tests had normal results. The advanced diagnostics revealed elevated creatine kinase values between 300 and 600 U/L. The electromyography (EMG) yielded clear evidence of myotonic discharges in both the arm and the leg.

Differential diagnosis: Known causes of recurrent laryngospasms or apneas in infancy include cardiac and respiratory diseases, infections, gastroesophageal reflux, cerebral disorders, or metabolic diseases.

Nondystrophic myotonias are rare with a prevalence of 1:100.000. Mutations in the skeletal muscle sodium (SCN4A) and chloride (CLCN1) channels have been identified.

Genetics: There are individual case reports of diagnosed neonatal nondystrophic myotonia, in which a mutation in the SCN4A gene on chromosome 17q23 was detected. In our patient, a heterozygote mutation was found in the SCN4A gene c.3917G > A;p.Gly1306Glu on chromosome 17q23-q25.3. The disease has an autosomal-dominant inheritance pattern.

Therapy: Some pharmacological treatments have proven efficacy in myotonic sodium channelopathies by blocking the sodium channel. Our patient was treated with carbamazepine (20 mg/kg/d). The treatment reduced the number and severity of daily episodes and was well tolerated.

Discussion: Apnea episodes with cyanosis in neonates and infants are a common phenomenon with a large differential diagnostic spectrum. A congenital myotonia caused by a mutation in the gene SCN4A is a rare disease, but it is easily detected by EMG. Early pharmacological therapy can reduce the frequency of episodes, symptoms, and prevent intensive care procedures. Because of the diverse clinical manifestations of channelopathies the prognosis of the disease is difficult to predict.

Keywords: apnoea, myotonia, SCN4A mutation.