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

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

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Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
CHU-Sainte Justine Research Centre, University of Montreal, Montreal, Quebec, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Department of Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.


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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