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

TitleKaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails.
Publication TypeJournal Article
Year of Publication2017
AuthorsKariminejad, A, Ajeawung, NFonya, Bozorgmehr, B, Dionne-Laporte, A, Molidperee, S, Najafi, K, Gibbs, RA, Lee, BH, Hennekam, RC, Campeau, PM
JournalJ Hum Genet
Date Published2017 Apr
KeywordsAbnormalities, Multiple, Adult, Carrier Proteins, Child, Child, Preschool, Diagnosis, Differential, Eczema, Eye Abnormalities, Face, Facies, Female, Growth Disorders, Hand Deformities, Congenital, Humans, Intellectual Disability, Karyotype, Limb Deformities, Congenital, Male, Microcephaly, Micrognathism, Mutation, Neck, Pathology, Molecular, Sequence Analysis, DNA, Ubiquitin-Protein Ligases

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.

Alternate JournalJ. Hum. Genet.
PubMed ID28003643
PubMed Central IDPMC5370204
Grant ListU54 HG006542 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 HD024064 / HD / NICHD NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
P30 AI036211 / AI / NIAID NIH HHS / United States
S10 RR024574 / RR / NCRR NIH HHS / United States