A novel ASCC1 splice-site variant broadens the phenotypic spectrum of spinal muscular atrophy with congenital bone fractures type 2.
Justyna Paprocka, Adrianna Ściślicka-Stelmach, Dominika Bieczek et al.
✦ AI-curated · Sources linked
Case in brief
A 7-year-old girl presented with generalized hypotonia, areflexia, and progressive respiratory insufficiency requiring tracheostomy and gastrostomy, but notably lacked congenital fractures, which are typical in spinal muscular atrophy with congenital bone fractures type 2 (SMABF2). Genetic analysis revealed a novel homozygous intronic donor-site variant in ASCC1, broadening the phenotypic spectrum of this disorder.
What made this case unusual
The absence of congenital fractures in a patient with a novel ASCC1 variant is atypical for SMABF2, suggesting variability in the phenotype associated with different ASCC1 mutations.
Diagnostic / clinical pearl
Clinicians should consider that not all ASCC1 variants lead to a classic loss-of-function phenotype, as evidenced by atypical presentations like the absence of congenital fractures.
Why it matters
This case highlights the importance of genetic testing in understanding the diverse phenotypic expressions of ASCC1-related disorders, which may influence management and prognosis.