X-linked myotubular myopathy in a neonate: a case report and literature review

X-linked centronuclear myopathy (XLCNM) is a rare congenital neuromuscular disorder caused by pathogenic variants in MTM1, typically presenting with severe neonatal hypotonia, respiratory failure, and poor survival. Early diagnosis is essential for prognosis and genetic counseling, though clinical recognition is often challenging.

We report a male infant, born at 38 + 1 weeks via cesarean section, who presented immediately after birth with apnea, cyanosis, hypotonia, and poor responsiveness. Despite resuscitation and intensive care for neonatal asphyxia and sepsis, he remained ventilator-dependent with persistent hypotonia and feeding difficulties. Laboratory evaluation showed anemia of chronic disease, hypoproteinemia, vitamin D insufficiency, and mild hepatic dysfunction. Imaging revealed laryngomalacia and a patent foramen ovale. Given the family history of neonatal death in a male sibling, whole-exome sequencing (WES) was performed and identified a hemizygous nonsense mutation in MTM1 (NM_000252.2): c.373C > T (p.Gln125Ter), confirming XLCNM. Maternal heterozygosity was verified by Sanger sequencing, consistent with X-linked recessive inheritance. In view of the severe clinical course and poor prognosis, the family declined further treatment. The patient was discharged for palliative care and died shortly after from respiratory failure.

This case reveals the importance of early recognition and genetic diagnosis of XLCNM, particularly in neonates with unexplained hypotonia and a suggestive family history. Through our literature review, we emphasize the need for heightened clinical awareness, summarize current therapeutic and research advances, and discusses supportive strategies that may optimize survival and quality of life in affected infants.