Serpentine Fibula Polycystic Kidney Syndrome is Part of the Phenotypic Spectrum of Hajdu-Cheney Syndrome

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2011 Jun 30

PMID 21712856

Citations 33

Authors

Mary J Gray

Chong Ae Kim

Debora Romeo Bertola

Paula Ricci Arantes

Helen Stewart

Michael A Simpson

Melita D Irving

Stephen P Robertson

Affiliations

Soon will be listed here.

Abstract

Serpentine fibula polycystic kidney syndrome (SFPKS; MIM600330) is a rare skeletal dysplasia that has polycystic kidneys and dysmorphic facies as additional defining phenotypic components. The nosological classification of this disease has been debated as the condition shares features common to other skeletal dysplasias such as Melnick Needles syndrome (MNS; MIM309350) and Hajdu-Cheney Syndrome (HCS; MIM102500). Here, two previously reported cases of SFPKS are presented with emphasis on their phenotypic evolution. With the recent discovery that HCS is caused by mutations in NOTCH2, DNA from the both cases was examined and both were found to have truncating mutations in exon 34 of NOTCH2. The phenotypic evolution of SFPKS and this molecular analysis strongly suggest that SFPKS is part of the phenotypic spectrum of HCS and should no longer be classified as a distinct disease entity.

Citing Articles

Molecular landscape of congenital vertebral malformations: recent discoveries and future directions.

Szoszkiewicz A, Bukowska-Olech E, Jamsheer A Orphanet J Rare Dis. 2024; 19(1):32.

PMID: 38291488 PMC: 10829358. DOI: 10.1186/s13023-024-03040-0.

Hajdu-Cheney syndrome with a novel variant in NOTCH2 gene: A case report.

Abdelkarim M, Alageel D, Ahsan F, Alhuthil R, Alsarhani H, Alsagheir A Bone Rep. 2023; 19:101709.

PMID: 37664144 PMC: 10474580. DOI: 10.1016/j.bonr.2023.101709.

Hajdu-Cheney syndrome with atypical cardiovascular abnormalities.

Ekure E, Sokunbi O, Kruszka P, Muenke M, Adeyemo A Am J Med Genet A. 2022; 191(1):271-274.

PMID: 36301051 PMC: 9742292. DOI: 10.1002/ajmg.a.63013.

Progress and Current Status in Hajdu-Cheney Syndrome with Focus on Novel Genetic Research.

Aida N, Ohno T, Azuma T Int J Mol Sci. 2022; 23(19).

PMID: 36232677 PMC: 9570194. DOI: 10.3390/ijms231911374.

Pathogenic Novel Heterozygous Variant c.1076c>T p. (Ser359Phe) chr1: 120512166 in NOTCH2 Gene, Type 2 Alagille Syndrome Causing Neonatal Cholestasis: A Case Report.

Uddin M, Al Fulayyih S, Al Denaini F, Al Hatlani M Am J Case Rep. 2022; 23:e935840.

PMID: 36201396 PMC: 9552858. DOI: 10.12659/AJCR.935840.

References

Kaplan P, Ramos F, Zackai E, Bellah R, Kaplan B . Cystic kidney disease in Hajdu-Cheney syndrome. Am J Med Genet. 1995; 56(1):25-30. DOI: 10.1002/ajmg.1320560108. View

Brennan A, Pauli R . Hajdu--Cheney syndrome: evolution of phenotype and clinical problems. Am J Med Genet. 2001; 100(4):292-310. DOI: 10.1002/1096-8628(20010515)100:4<292::aid-ajmg1308>3.0.co;2-4. View

Currarino G . Hajdu-Cheney syndrome associated with serpentine fibulae and polycystic kidney disease. Pediatr Radiol. 2008; 39(1):47-52. DOI: 10.1007/s00247-008-0992-9. View

Isidor B, Lindenbaum P, Pichon O, Bezieau S, Dina C, Jacquemont S . Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat Genet. 2011; 43(4):306-8. DOI: 10.1038/ng.778. View

McDaniell R, Warthen D, Sanchez-Lara P, Pai A, Krantz I, Piccoli D . NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006; 79(1):169-73. PMC: 1474136. DOI: 10.1086/505332. View

Hamada Y, Kadokawa Y, Okabe M, Ikawa M, Coleman J, Tsujimoto Y . Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development. 1999; 126(15):3415-24. DOI: 10.1242/dev.126.15.3415. View

Exner G . Serpentine fibula--polycystic kidney syndrome. A variant of the Melnick-Needles syndrome or a distinct entity?. Eur J Pediatr. 1988; 147(5):544-6. DOI: 10.1007/BF00441987. View

Majewski F, Enders H, Ranke M, Voit T . Serpentine fibula--polycystic kidney syndrome and Melnick-Needles syndrome are different disorders. Eur J Pediatr. 1993; 152(11):916-21. DOI: 10.1007/BF01957530. View

Albano L, Bertola D, Barba M, Valente M, Robertson S, Kim C . Phenotypic overlap in Melnick-Needles, serpentine fibula-polycystic kidney and Hajdu-Cheney syndromes: a clinical and molecular study in three patients. Clin Dysmorphol. 2006; 16(1):27-33. DOI: 10.1097/01.mcd.0000228418.74413.52. View

10.

Warman M, Cormier-Daire V, Hall C, Krakow D, Lachman R, Lemerrer M . Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011; 155A(5):943-68. PMC: 3166781. DOI: 10.1002/ajmg.a.33909. View

11.

Dereymaeker A, Christens J, EECKELS R, Heremans G, Fryns J . Melnick-Needles syndrome (osteodysplasty). Clinical and radiological heterogeneity. Helv Paediatr Acta. 1986; 41(4):339-51. View

12.

Rosser E, Mann N, Hall C, Winter R . Serpentine fibula syndrome: expansion of the phenotype with three affected siblings. Clin Dysmorphol. 1996; 5(2):105-13. DOI: 10.1097/00019605-199604000-00002. View

13.

Simpson M, Irving M, Asilmaz E, Gray M, Dafou D, Elmslie F . Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet. 2011; 43(4):303-5. DOI: 10.1038/ng.779. View

14.

Fryns J . Serpentine fibula syndrome: a variant clinical presentation of Hajdu-Cheney syndrome?. Clin Dysmorphol. 1997; 6(3):287-8. DOI: 10.1097/00019605-199707000-00016. View

15.

Ramos F, Kaplan B, Bellah R, Zackai E, Kaplan P . Further evidence that the Hajdu-Cheney syndrome and the "serpentine fibula-polycystic kidney syndrome" are a single entity. Am J Med Genet. 1998; 78(5):474-81. DOI: 10.1002/(sici)1096-8628(19980806)78:5<474::aid-ajmg14>3.0.co;2-c. View