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

J Hum Genet 2017 Apr 22;62(4):465-471. Epub 2016 Dec 22.

CHU-Sainte Justine Research Centre, 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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http://dx.doi.org/10.1038/jhg.2016.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370204PMC
April 2017
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References

(Supplied by CrossRef)

RL Kaufman et al.
Birth Defects Orig. Artic. Ser. 1971

L Basel-Vanagaite et al.
Am. J. Hum. Genet. 2012

L Basel-Vanagaite et al.
Hum. Genet. 2014

E Flex et al.
J. Med. Genet. 2013

CR Pedurupillay et al.
Am. J. Med. Genet. A 2015

HV Toriello et al.
Am. J. Med. Genet. 2003

I Buntinx et al.
Am. J. Med. Genet. 1990

PM Campeau et al.
Hum. Mol. Genet. 2012

K Wang et al.
Nucleic acids Res. 2010

D Popovic et al.
Nat. Med. 2014

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