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Case Reports
. 2020 Sep 18;46(1):135.
doi: 10.1186/s13052-020-00901-9.

Total colonic aganglionosis and cleft palate in a newborn with Janus-cysteine 618 mutation of RET proto-oncogene: a case report

Ingrid Anne Mandy Schierz  1 , Marcello Cimador  2 , Mario Giuffrè  3 , Claudia Maria Aiello  3 , Vincenzo Antona  3 , Giovanni Corsello  3 , Ettore Piro  3
Affiliations
Case Reports

Total colonic aganglionosis and cleft palate in a newborn with Janus-cysteine 618 mutation of RET proto-oncogene: a case report

Ingrid Anne Mandy Schierz et al. Ital J Pediatr. .

Abstract

Background: Hirschsprung disease, the most important congenital colonic dysmotility in children results from neural crest migration, differentiation, proliferation, or apoptosis defects where the rearranged during transfection (RET)-Protooncogene pathway has a central role. Although palatal and retinal anomalies in the context of chromosomopathies and some mono-/oligogenic syndromes are reported associated with Hirschsprung disease the role of inactivating RET mutations in these cases is not clarified.

Case presentation: We report on a dysmorphic newborn with cleft palate and palatal synechia, who showed intestinal obstruction after 24 h of life. Transient ileostomy and surgical biopsies were performed to diagnose aganglionosis of the colon and last ileal loop. No chromosomal anomalies or copy number variations were found. We identified a paternal heterozygous germline mutation c.1852 T > C, which results in the substitution of cysteine by arginine in the RET-receptor tyrosine kinase (p.C618R mutation). There was no family history of Hirschsprung disease, but the father underwent surgery for medullary thyroid carcinoma and was affected by retinal dystrophy.

Conclusions: The occurrence of Hirschsprung disease and carcinoma shows how a single mutation may be responsible for adverse effects: gain and loss of function of the same receptor. Furthermore, it would be interesting to study its dual role in face and retina embryology, and to extend targeted investigations of RET hotspots in these developmental abnormalities to facilitate counselling, follow-up, and tumor prevention. Complex surgical procedures and genetic testing as well as socio-economic impact are a challenge for familiar compliance.

Keywords: Case-report; Congenital digestive system abnormalities; Hirschsprung disease; Neurocristopathy; REarranged during Transfection.

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Conflict of interest statement

Not applicable.

Figures

Fig. 1
Fig. 1
Plain abdominal radiogram shows distended small bowel loops, distal obstruction, and absent rectal gasification, consisting with total colonic aganglionosis. There are no peritoneal free fluid or air and no associated skeletal anomalies or maturation defects, except for the still absent first coccygeal ossification center
See this image and copyright information in PMC

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