FLNA – Congenital Short Bowel Syndrome

Filamin A (FLNA) encodes a cytoskeletal cross-linking protein essential for cellular scaffolding and organ morphogenesis. Congenital short bowel syndrome (MONDO:0014097) is defined by a markedly reduced small intestine length at birth, leading to malabsorption, diarrhea, weight loss, and intestinal obstruction. In a single kindred, two male siblings exhibited severe CSBS: one infant suffered massive intestinal torsion with only 60 cm of residual small bowel and died postoperatively, while his brother presented with recurrent abdominal pain, chronic diarrhea, and weight loss. Genetic analysis revealed a segregating FLNA mutation in both affected children and their mother, consistent with X-linked recessive inheritance (PMID:39173431). Diagnosis was confirmed via exploratory surgery, and there are currently no consensus nutritional or surgical guidelines specific to FLNA-related CSBS.

Based on ClinGen criteria, the FLNA–CSBS association is classified as Limited owing to a single family harboring two affected siblings, absence of unrelated probands, and lack of functional studies. The inheritance mode is X-linked recessive, with carrier mothers asymptomatic and two hemizygous offspring affected. No experimental or in vivo models have evaluated the impact of FLNA variants on intestinal development in CSBS. Additional unrelated cases, extended segregation, and mechanistic data are required to upgrade the classification. Despite limited evidence, FLNA genetic testing should be considered in familial CSBS presentations. Key Take-home: FLNA mutations represent a rare but emerging genetic etiology for congenital short bowel syndrome, warranting targeted genetic analysis and multidisciplinary management.

References

• International journal of surgery case reports • 2024 • Congenital short bowel syndrome: Cases series in the same family and review of literature. PMID:39173431

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