A Novel Mutation Associated with Severe Centronuclear Myopathy in a Neonate
Year: 2024
Type: article
Study design: Case Report
Abstract: Sir, Centronuclear myopathy (OMIM 310400) belongs to the group of congenital myopathies characterized by centrally placed nuclei on muscle biopsy. It can be X-linked recessive, autosomal dominant, or recessive. To date, more than 250 pathogenic variants of the MTMN1 gene have been identified and published in the medical literature.[1] Here, we describe the clinical highlights of a male newborn from North India who presented with severe features of X-linked recessive centronuclear myopathy, and after a thorough evaluation, was proven to have a novel mutation c.610G>T, (pVal204Phe), which has been described as pathogenic. The proband, a male neonate, was referred to our institute on day 21 of life for evaluation of generalized hypotonia since birth. He is firstborn to a nonconsanguineously married, healthy couple. The mother reported decreased perception of fetal movements, and on ultrasound, she had polyhydramnios. At admission, head-to-foot examination revealed dolichocephaly, myopathic facies, long philtrum, pouted upper lips, retrognathia with high-arched palate, pectus excavatum, wrist drop in both hands, less prominent dorsal creases on the fingers, shiny skin over the fingers, a prominent dorsal transverse crease over the foot proximal to the toes, clinodactyly of the fourth and fifth toes, and bilateral undescended testes [Figure 1]. The baby had shallow breathing with poor respiratory efforts, poor state-to-state variability, normal extraocular movements, weak gag reflex, cortical thumb with fisting, severe axial and appendicular hypotonia, and absent primitive reflexes with preserved deep tendon reflexes. Baseline history and clinical examination ruled out any neuromuscular weakness in both parents.Figure 1: Clinical picture showing pectus excavatumClinical possibilities considered were congenital myopathies, spinal muscular atrophy (SMA), SMA with respiratory distress (SMARD), and Prader–Willi syndrome. Fluoroscopy confirmed right hemi-diaphragmatic palsy. Magnetic resonance imaging of the brain was normal. Surprisingly, CK-MB levels were within normal limits. Nerve conduction studies were suggestive of axonal polyneuropathy. An electromyography could not be performed owing to logistic reasons. Initial genetic evaluation using Multiplex Ligation-dependent Probe Amplification (MLPA) was negative for SMA, SMARD, and Prader–Willi syndrome. Subsequently, Next-Generation Sequencing (NGS)-based panel analysis using clinical exome sequencing showed the presence of a hemizygous missense variation (c.610G>T) (pVal204Phe) in exon 8 of the MTMN1 gene. The variation was classified as likely pathogenic per the American College of Medical Genetics guidelines.[2] In the light of supportive clinical findings and a conclusive genetic report, a muscle biopsy was deferred. The lack of common clinical features and the advanced nature of the disease in the neonatal period associated with the mutation make it important to identify such patients. In this way, we hope that our findings could contribute to the diagnostic process of subsequent patients. Though clinical exome sequencing shows a novel pathogenic mutation segregation, targeted Sanger sequencing studies should be done to confirm the real pathogenicity. Unfortunately, further parental genetic evaluation could not be performed owing to financial constraints. Declaration Consent was taken from parents for publication of photographs and data. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Neurology India
Authors: Prabakaran Gangadaran, Sushil Choudhary
Institution: All India Institute of Medical Sciences Jodhpur
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4405507468