Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails

J Hum Genet. 2017 Apr;62(4):465-471. doi: 10.1038/jhg.2016.151. Epub 2016 Dec 22.

Abstract

Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay allowed us to make a diagnosis of KOS. In conclusion, our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Adult
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • Diagnosis, Differential*
  • Eczema / diagnosis
  • Eczema / genetics
  • Eczema / physiopathology
  • Eye Abnormalities / diagnosis
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / physiopathology
  • Face / abnormalities
  • Face / physiopathology
  • Facies
  • Female
  • Growth Disorders / diagnosis
  • Growth Disorders / genetics
  • Growth Disorders / physiopathology
  • Hand Deformities, Congenital / diagnosis
  • Hand Deformities, Congenital / genetics
  • Hand Deformities, Congenital / physiopathology
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Karyotype
  • Limb Deformities, Congenital / diagnosis
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / physiopathology
  • Male
  • Membrane Proteins
  • Microcephaly / diagnosis
  • Microcephaly / genetics*
  • Microcephaly / physiopathology
  • Micrognathism / diagnosis
  • Micrognathism / genetics
  • Micrognathism / physiopathology
  • Mutation
  • Neck / abnormalities
  • Neck / physiopathology
  • Nerve Tissue Proteins
  • Pathology, Molecular
  • Sequence Analysis, DNA
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • TBC1D24 protein, human
  • UBE3B protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Coffin-Siris syndrome
  • Dubowitz syndrome
  • Kaufman oculocerebrofacial syndrome