Hereditary Multiple Intestinal Atresia With a Novel TTC7A Pathogenic Variant: Gastrointestinal Manifestations in Two...

Hereditary multiple intestinal atresia (HMIA) with TTC7A mutation is caused by homozygous or compound heterozygous TTC7A gene mutation. It is characterized by multiple small and large intestinal atresias and/or stenoses. TTC7A mutation is described in some patients with inflammatory bowel disease and mild-severe forms of severe combined immunodeficiency without intestinal atresia or stenosis. We present 2 cases of intestinal atresia and documented TTC7A mutation with a novel variant. Both cases had different clinical and pathological manifestations. The first case is a male infant born at 35 weeks of gestation with failure to pass meconium. Intestinal biopsy reveals apoptotic enteropathy with villous atrophy and increased mucosal eosinophils. The second case is referred at birth for antenatally detected umbilical hernia, polyhydramnios and possible upper intestinal obstruction. The resected specimen reveals ileal atresia with partial villous atrophy, decreased number of lamina propria inflammatory cells and absence of plasma cells. In conclusion, these cases reflect an emerging TTC7A pathogenic variant with different histological manifestations and leads to characterization as immune dysregulation disorder. There is a need to differentiate TTC7A mutation associated ones from cases labeled as very early onset IBD and rule out other hereditary immunodeficiencies.