UNASSIGNED: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive hereditary disease. Immunoglobulin μ-binding protein 2 (IGHMBP2) gene mutations are the main cause of SMARD1.
UNASSIGNED: Here we describe a female infant with SMARD1 carrying heterozygous mutations in IGHMBP2 genes, c.1334A > C(p.His445Pro) and c.1666C > G(p.His556Asp), which were inherited from both parents. Clinical presentations included frequent respiratory infections, respiratory failure, distal limb muscle weakness, and fat pad found at the distal toe.
UNASSIGNED: c.1666C > G(p.His556Asp) is a novel site mutation in IGHMBP2. This case expanded knowledge on the genetic profile of SMARD1 and it provides a basis for genetic testing of parents and for genetic counseling to assess the risk of fetal disease.

A rare autosomal recessive genetic disease is spinal muscular atrophy with respiratory distress type 1 (SMARD 1; OMIM #604320), which is characterized by progressive distal limb muscle weakness, muscular atrophy, and early onset of respiratory failure. Herein, we report the case of a 4-month-old female infant with SMARD type 1 who was admitted to our hospital owing to unexplained distal limb muscle weakness and early respiratory failure. This report summarizes the characteristics of SMARD type 1 caused by heterozygous variation in the immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene by analyzing its clinical manifestations, genetic variation characteristics, and related examinations, aiming to deepen clinicians\' understanding of the disease, assisting pediatricians in providing medical information to parents and improving the decision-making process involved in establishing life support.

Immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) mutations are associated with partial continuum between two extremes of rapidly lethal disorder of spinal muscular atrophy with respiratory distress type 1 (SMARD1), with infantile axonal neuropathy, diaphragmatic weakness and commonly death before 1 year of age, and Charcot-Marie-Tooth disease (CMT) type 2S with slowly progressive weakness and sensory loss but no significant respiratory compromise. We present an atypical case of CMT2S. A 9 month old boy presented with bilateral feet deformities and axonal neuropathy. Genetic testing revealed two heterozygous variants in the IGHMBP2 gene: c.1156 T > C p.(Trp386Arg) in exon 8 and c.2747G > A p.(Cys916Tyr) in exon 14, that were inherited from his father and mother respectively. At 9 years, he developed diaphragmatic weakness, following which he was established on non-invasive ventilation. Our case emphasizes the importance of life long respiratory surveillance for patients with CMT2S and expands the phenotype of this condition.