Neonatal Hypotonia with an Incomplete Genotype–Phenotype Correlation: A Diagnostic Challenge Suggestive of Ullrich Congenital Muscular Dystrophy

A bstract Neonatal hypotonia represents a diagnostic challenge in pediatric neuroscience, particularly when genetic investigations fail to provide definitive molecular confirmation. Ullrich congenital muscular dystrophy, a collagen VI-related disorder, often presents early with hypotonia and respiratory involvement but may evade complete detection on routine sequencing. We describe the case of a 10-day-old female neonate born to consanguineous parents who presented with severe generalized hypotonia, feeding difficulty, and weak respiratory effort. Two previous siblings had died in early infancy with similar features. Neurological examination revealed marked hypotonia with preserved reflexes and distal joint hyperlaxity. Creatine kinase and metabolic evaluation were normal. Whole-exome sequencing identified a heterozygous pathogenic COL6A2 variant, but no second pathogenic allele was detected. Supportive multidisciplinary management was initiated. On follow-up, progressive weakness and impaired swallowing necessitated tube feeding and intensified respiratory surveillance. This case highlights the importance of phenotype-driven diagnosis in neonatal neuromuscular disorders and underscores the limitations of whole-exome sequencing in collagen VI-related dystrophies. Clinical judgment remains central when managing infants with severe hypotonia and inconclusive genetic results.