Oblique facial clefts in Johanson-Blizzard syndrome

Am J Med Genet A. 2016 Jun;170(6):1495-501. doi: 10.1002/ajmg.a.37630. Epub 2016 Mar 17.

Abstract

Johanson-Blizzard syndrome (JBS) is considered as an infrequent, but clinically easily recognizable autosomal recessive entity by the pathognomonic combination of congenital exocrine pancreatic insufficiency and hypoplastic alae nasi, in addition to other distinctive findings such as scalp defects, hypothyroidism, and rectourogenital malformations. There are few reports of patients with JBS in association with facial clefting, referring all to types 2 to 6 of Tessier's classification that can be characterized properly as oblique facial clefts (OFCs). We describe the clinical aspects in four patients with JBS and extensive OFCs. In all of them, the diagnosis of JBS was confirmed by the demonstration of homozygous or compound-heterozygous mutations in the UBR1 gene. Additionally, we review three previously reported cases of JBS with OFCs. Taking into account a number of approximately 100 individuals affected by JBS that have been published in the literature we estimate that the frequency of OFCs in JBS is between 5% and 10%. This report emphasizes that extensive OFCs may be the severe end of the spectrum of facial malformations occurring in JBS. No obvious genotype phenotype correlation could be identified within this cohort. Thus, UBR1 should be included within the list of contributory genes of OFCs, although the exact mechanism remains unknown. © 2016 Wiley Periodicals, Inc.

Keywords: Tessier classification; UBR1; cleft lip; cleft palate; oblique facial clefts.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Alleles
  • Anus, Imperforate / diagnosis*
  • Anus, Imperforate / genetics*
  • Cleft Palate / diagnosis*
  • Cleft Palate / genetics*
  • Consanguinity
  • Craniofacial Dysostosis / diagnosis*
  • Craniofacial Dysostosis / genetics*
  • DNA Mutational Analysis
  • Diagnostic Imaging
  • Ectodermal Dysplasia / diagnosis*
  • Ectodermal Dysplasia / genetics*
  • Eye Abnormalities / diagnosis*
  • Eye Abnormalities / genetics*
  • Female
  • Genetic Association Studies*
  • Genotype
  • Growth Disorders / diagnosis*
  • Growth Disorders / genetics*
  • Hearing Loss, Sensorineural / diagnosis*
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Hypothyroidism / diagnosis*
  • Hypothyroidism / genetics*
  • Infant, Newborn
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Introns
  • Male
  • Maxillofacial Abnormalities / diagnosis*
  • Maxillofacial Abnormalities / genetics*
  • Mutation
  • Nose / abnormalities*
  • Pancreatic Diseases / diagnosis*
  • Pancreatic Diseases / genetics*
  • Phenotype
  • Ubiquitin-Protein Ligases / genetics

Substances

  • UBR1 protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Johanson Blizzard syndrome
  • Oculomaxillofacial dysostosis