Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Centronuclear myopathy (CNM) is a group of rare inherited muscle disorders.
• Dynamin 2 (DNM2) mutations are associated with some forms of CNM.
• The phenotypic spectrum of DNM2-related CNM is not fully characterized.

Purpose of the Study:

• To investigate the genetic basis and clinical presentation of centronuclear myopathy in young patients.
• To expand the understanding of the phenotypic spectrum of dynamin 2-related centronuclear myopathy.

Main Methods:

• Genetic analysis to identify mutations in the dynamin 2 (DNM2) gene.
• Clinical assessment of patients, including neurological examination and muscle weakness evaluation.
• Electrophysiological studies and muscle biopsy for diagnostic confirmation.

Main Results:

• Four heterozygous DNM2 mutations were identified in five patients aged 1 to 15 years.
• Patients presented with neonatal hypotonia and weak suckling, with subsequent improvement.
• Muscle weakness was prominent in lower limbs, with facial weakness, ptosis, and ophthalmoparesis in most.
• Muscle biopsies revealed central nuclei and type 1 fiber hypotrophy/predominance.

Conclusions:

• The study identifies novel heterozygous DNM2 mutations associated with a severe neonatal phenotype of centronuclear myopathy.
• This expands the known clinical spectrum of DNM2-related CNM, including a more severe presentation than previously described.
• Findings highlight the importance of genetic testing for DNM2 in neonatal hypotonia cases.