A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome)
- Alice S Brooksa,b,
- Martijn H Breuninga,c,
- Jan Osingad,
- Jasper J vd Smagtc,
- Corine E Catsmane,
- Charles H C M Buysd,
- Carel Meijersb,f,
- Robert M W Hofstrad
- aDepartment of Clinical Genetics, Erasmus University and University Hospital, Rotterdam, The Netherlands, bDepartment of Paediatric Surgery, Erasmus University and University Hospital, Rotterdam, The Netherlands, cDepartment of Clinical Genetics, University Hospital Leiden, The Netherlands, dDepartment of Medical Genetics, University of Groningen, The Netherlands, eDepartment of Child Neurology, Erasmus University and University Hospital, Rotterdam, The Netherlands, fDepartment of Cell Biology and Genetics, Erasmus University and University Hospital, Rotterdam, The Netherlands
- Dr Meijers, Department of Cell Biology and Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
- Received 10 June 1998
- Revised 22 October 1998
Abstract
Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family. A fourth child showed similar clinical features, with the exception of Hirschsprung disease. The association of these abnormalities in these children represents the Goldberg-Shprintzen syndrome (OMIM 235730).
Mutation scanning of genes potentially involved in Hirschsprung disease, RET, GDNF, EDN3, and EDNRB, showed a sequence variant, Ser305Asn, in exon 4 of the EDNRB gene in the index patient of this family. The Ser305Asn substitution present in two of the four patients and four healthy relatives and absent in one of the remaining two patients illustrates the difficulties in interpreting the presence of mutations in families with Hirschsprung disease. It is unlikely that the EDNRB variant contributes to the phenotype. This consanguineous family might be useful for the identification of a Goldberg-Shprintzen locus.
