Case of autosomal-recessive spinal muscular atrophy with respiratory distress type 1 caused by compound heterozygous mutations in immunoglobulin-binding protein 2 gene: expansion in clinical features

Background
The etiological factors for early-onset infantile hypotonia with respiratory distress are variable. Spinal muscle atrophy with respiratory-distress type 1 (SMARD1) is usually presented with early-onset severe hypotonia and respiratory insufficiency that may require mechanical ventilation.
Patients and methods
Herein, we report on an Egyptian male infant who was born to nonconsanguineous parents, presented at the age of 2 months with acute onset of respiratory distress and severe hypotonia and required mechanical ventilatory support. As an expansion to the typical SMARD1 clinical features, hepatomegaly, elevated liver transaminases, and subdural hygroma were identified. Additionally, computed tomography chest showed pulmonary consolidation without evidence of diaphragmatic paralysis. The patient was mechanically ventilated and fed by nasogastric tube. There were multiple trials of extubation, which failed and tracheostomy was done. The patient died at the age of 11-month old. Whole-exome sequencing was done for the index patient and followed by variant filtration. Parental segregation was done to evaluate the phase of the detected variants.
Results
Whole-exome sequencing revealed two heterozygous variants in the immunoglobulin-binding protein 2 () gene, c.138 T>A and c.1616C>T, a pathogenic variant, and another of uncertain significance, respectively. In addition, a variant of uncertain significance was identified in gene (c.389 A>T). Biallelic variants are causative for SMARD1 and axonal Charcot–Marie–Tooth disease type 2S. Segregation study and clinical presentation prioritize the compound heterozygous variants in gene (c.138 T>A) and (c.1616C>T) as the causing disease molecular pathology.
Conclusion
Both SMARD1 and congenital myasthenic syndromes are possible genetic diagnoses for this patient. However, the clinical phenotype was more compatible with SMARD1. Nevertheless, the additional manifestations such as microcephaly, hepatomegaly, hypothyroidism, and neuroimaging were not featured in SMARD1.