A female with complete lack of Müllerian fusion, postaxial polydactyly, and tetralogy of fallot: Genetic heterogeneity of McKusick–Kaufman syndrome or a unique syndrome?
- 15 July 2004
- journal article
- case report
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 129A (1), 69-72
- https://doi.org/10.1002/ajmg.a.30071
Abstract
We report a 19‐year‐old, non‐Amish Caucasian female patient with primary amenorrhea caused by complete lack of Müllerian fusion with vaginal agenesis or Müllerian aplasia (MA), postaxial polydactyly (PAP), and tetralogy of Fallot. The genital tract anomaly of MA with and without renal or skeletal anomalies comprises Mayer–Rokitansky–Kuster–Hauser syndrome, which has not been reported with tetralogy of Fallot. The phenotypic triad of anomalies most closely resembled McKusick–Kaufman syndrome (MKS; OMIM 236700), a rare multiple congenital anomaly syndrome comprised of hydrometrocolpos (HMC), PAP, and congenital heart malformation that is inherited in an autosomal recessive pattern. While upper reproductive tract anomalies have not been reported with MKS, they have been reported with Bardet–Biedl syndrome (BBS), a syndrome that significantly overlaps with MKS. Both MKS and BBS can be caused by mutations in the MKKS or BBS6 gene on chromosome 20p12 and BBS is also associated with mutations in other genes (BBS1, BBS2, BBS4, and BBS7). To address this heterogenity, we sequenced the causative genes in MKS and BBS but no mutations in these five genes were identified. Fluorescence in situ hybridization (FISH) excluded large deletions of chromosome 20p12 and microsatellite marker studies confirmed biparental inheritance for all of the known BBS loci. The dual midline fusion defects of tetralogy of Fallot and MA suggests that either this patient has a unique syndrome with a distinct genetic etiology or that she has a genetically heterogeneous or variant form of MKS. Published 2004 Wiley‐Liss, Inc.Keywords
This publication has 41 references indexed in Scilit:
- Identification of a Novel Bardet-Biedl Syndrome Protein, BBS7, That Shares Structural Features with BBS1 and BBS2American Journal of Human Genetics, 2003
- Genetic and Mutational Analyses of a Large Multiethnic Bardet-Biedl Cohort Reveal a Minor Involvement of BBS6 and Delineate the Critical Intervals of Other LociAmerican Journal of Human Genetics, 2001
- Familial Tetralogy of Fallot caused by mutation in the jagged1 geneHuman Molecular Genetics, 2001
- M??llerian Agenesis: Etiology, Diagnosis, and ManagementObstetrical & Gynecological Survey, 2000
- Atrioventricular canal defect and postaxial polydactyly indicating phenotypic overlap of Ellis-van Creveld and Kaufman-McKusick syndromesPediatric Cardiology, 1997
- Report from the workshop on Pallister-Hall syndrome and related phenotypesAmerican Journal of Medical Genetics, 1996
- MURCS association: case report and review.Journal of Medical Genetics, 1996
- Cardiac abnormalities in the Bardet‐Biedl syndrome: Echocardiographic studies of 22 patientsAmerican Journal of Medical Genetics, 1994
- Hydrometrocolpos, postaxial polydactyly, congenital heart disease, and anomalies of the gastrointestinal and genitourinary tracts: A rare autosomal recessive syndromeEuropean Journal of Pediatrics, 1981
- Congenital Absence of the VaginaAnnals of Internal Medicine, 1976