Neonatal intestinal obstruction in Hoyeraal–Hreidarsson syndrome with novel RTEL1 variants

Abstract

Hoyeraal-Hreidarsson syndrome (HHS) is an early-onset telomere biology disorder (TBD), characterized by intrauterine growth retardation (IUGR), cerebellar hypoplasia, bone marrow failure (BMF), immunodeficiency, and gastroenteropathy. 1,2 There is scarce information about genotype-phenotype correlation among patients with 11 causative genes for dyskeratosis congenita (DC) or HHS. 3,4 Flow cytometry-fluorescence in situ hybridization (flow-FISH) analysis of peripheral blood lymphocytes effectively screens TBD, but age-dependent relative telomere lengths do not represent disease severity. [5][6][7] Enteropathy is not a specific sign of TBDs, but can precede the onset of BMF. 8 We describe a case of neonatal-onset bowel disease in a patient with two novel RTEL1 variants, whose cytopenias later developed.A 902-g, male proband was born at 29 weeks of gestation by cesarean section because of non-reassuring fetal status, IUGR, and hydrops fetalis with fetal ascites and oligohydramnios. There was no hydrops or asphyxia at birth. Within the first 24 hours of life prior to feeding, he presented with abdominal distention, pneumoperitoneum, small bowel obstruction, and perforation requiring an urgent surgical intervention. This infant had no structural or vascular anomalies of the gastrointestinal tract. Complete blood counts at birth were unremarkable, although elevated serum levels of immunoglobulin (Ig)M and IgA suggested prenatal inflammation or infection (Table S1). He remained to be hospitalized for 5 months to control feeding difficulty. After the hospital discharge, he showed delayed catch-up growth and received the regular vaccination program in Japan uneventfully without recurrent infections.