Hirschsprung's disease in a patient with translocation resulting in a partial trisomy of the long arm of chromosome

Abstract

Review of the literature reveals a relatively well defined phenotype associated with partial trisomies of chromosome 1q. We report a patient with the karyotype 46,XX, der(14) t(1;14) (q32.1;q32.3) who shows several of the features previously described in patients with partial trisomy of the distal part of chromosome 1q: Growth retardation, dysmorphic features including a high forehead, small ears and eyes, large anterior fontanel, pronounced nasal bridge with long nose, triangular mouth, micro-retrognathia, overlapping of the 3rd and 4th toe, clinodactyly of the 5th finger, sacral dimple and hirsutism. An echocardiogram revealed anomalous return of the upper left pulmonary vein and a large secundum atrial septal defect. On head ultrasound a left choroid plexus cyst was noted.In addition, the newborn manifested acute bowel obstruction on the third day of life due to Hirschsprung's disease (aganglionosis proven on biopsy). While other abnormalities of the gastrointestinal system such as pyloric stenosis and gallbladder abnormalities have been reported in partial trisomy 1q, to our knowledge, there are no previous reports of Hischsprung's disease in these patients.Hirschsprung's disease is a polygenic disorder. Several loci on different chromosomes (such as chromosomes 5, 10, 20, and especially the endothelin-B receptor gene on chromosome 13q22) have been associated with the condition. No links to either the long arm of chromosome 1 nor chromosome 14q have been reported. While a causative relationship between the partial trisomy 1q and the presence of aganglionosis of the colon can not be established in our patient at this point, the definition of the exact break points, comparison with the clinical phenotypes of patients with slightly different breakpoints and patients with Hirschsprung's disease without chromosomal abnormalities, and review of the genes assigned to the distal parts of the long arms of chromosomes 1 and 14 seem of interest and may provide further understanding of the pathophysiology of this trisomy and the associated gastrointestinal malformation.