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Renal‐hepatic‐pancreatic dysplasia: A sibship with skeletal and central nervous system anomalies and NPHP3 mutation
Author(s) -
Copelovitch Lawrence,
O'Brien Maureen M.,
Guttenberg Marta,
Otto Edgar A.,
Kaplan Bernard S.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35958
Subject(s) - medicine , anatomy , pathology , ciliopathy , foramen , nephronophthisis , maldevelopment , biology , biochemistry , gene , phenotype
We report on five consecutive sibs three with fatal renal‐hepatic‐pancreatic dysplastic (RHPD) syndrome and two pregnancies ending in early abortion. Three of the fetuses reached term and two survived for 15 and 58 days. They had diffusely cystic kidneys with absence of the distal collecting tubules, hepatic fibrosis, bile duct paucity, and pancreatic fibrosis with irregularly dilated ducts. These findings correspond to many of those reported by Ivemark et al. [Ivemark et al. (1959); Acta Paediat Scand 48: 1–11] as part of the RHPD syndrome. There are several notable differences in this family: one patient had hypocalvaria and a choroid plexus cyst at the right foramen of Luschka, multiple bone abnormalities including widened growth plates and abnormal development of the trabeculae of the ribs, “handle‐bar” clavicles, wedge defects of the inferior margin of several thoracic vertebrae; the second patient had hypocalvaria and abnormally developed brain with bilateral exposure of the insulae; and a third patient had anencephaly. Mutational analysis of the two who survived beyond post‐delivery demonstrated compound heterozygous novel frameshift mutations in the nephronophthisis type 3 gene ( NPHP3 ). © 2013 Wiley Periodicals, Inc.