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Case Reports
. 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

Ariana Kariminejad  1 , Norbert Fonya Ajeawung  2 , Bita Bozorgmehr  1 , Alexandre Dionne-Laporte  3 , Sirinart Molidperee  2 , Kimia Najafi  1 , Richard A Gibbs  4 , Brendan H Lee  5 , Raoul C Hennekam  6 , Philippe M Campeau  2   7
Affiliations
Case Reports

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

Ariana Kariminejad et al. J Hum Genet. 2017 Apr.

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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Conflict of interest statement

Authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Individual 1 and 2. (a) Individual 1 at 9 months, (b) frontal view of individual 2 at age ten, (c) individual 2 at age 16 years, (d) lateral view of individual 2 at 16 years, (e) note the absent terminal phalanx and nail of the fifth finger of left hand and terminal hypoplasia of other fingers, (f) hallux valgus developed after surgery to repair severe hallux varus.
Figure 2
Figure 2
X-rays of left hand and foot. (a) Note hypoplasia of terminal phalanges and absence of terminal phalanx of fifth finger. (b) Note severe hallux varus before surgery.
Figure 3
Figure 3
Sanger sequencing analysis and alignment of a segment of UBE3B HECT domain. (a) Sanger sequencing demonstrating heterozygous mutation in parents and homozygous deletion in proband. (b) Conservation of amino acids that are in close proximity to the active site of UBE3B HECT domain, including lys1047.
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