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

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.

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Acknowledgements

We thank the family for participating in this project, and The Réseau de Médecine Génétique Appliquée du Québec for help with bioinformatics analyses. NFA is funded by the CHU Sainte-Justine Foundation, the Fonds de recherche du Québec-Santé postdoctoral scholarship. PMC is funded by the Canadian Institutes of Health Research Grants CIHR RN315908 and RN324373, and the Fonds de recherche du Québec Santé grant FRQS 30647. This work was supported by the BCM Intellectual and Developmental Disabilities Research Center (HD024064) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, the BCM Advanced Technology Cores with funding from the NIH (AI036211, CA125123, and RR024574), the Rolanette and Berdon Lawrence Bone Disease Program of Texas, and the BCM Center for Skeletal Medicine and Biology and NIH grants U54 HG006542 (to RAG) and U54 HG003273-09 (to RAG).

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Correspondence to Philippe M Campeau.

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Kariminejad, A., Ajeawung, N., Bozorgmehr, B. et al. Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails. J Hum Genet 62, 465–471 (2017). https://doi.org/10.1038/jhg.2016.151

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