title: 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.
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.affiliation: CHU-Sainte Justine Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Norbert Fonya
authors.initials: NF
authors.lastname: Ajeawung
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Bozorgmehr
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dionne-Laporte
authors.affiliation: CHU-Sainte Justine Research Centre, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Sirinart
authors.initials: S
authors.lastname: Molidperee
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran.
authors.forename: Kimia
authors.initials: K
authors.lastname: Najafi
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Brendan H
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Hennekam
authors.affiliation: CHU-Sainte Justine Research Centre, University of Montreal, Montreal, Quebec, Canada.|Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Campeau
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004485:Eczema / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005145:Face / Q000002:abnormalities / Q000503:physiopathology; D019066:Facies; D005260:Female; D020690:GTPase-Activating Proteins; D006130:Growth Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D059785:Karyotype; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008844:Micrognathism / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D009333:Neck / Q000002:abnormalities / Q000503:physiopathology; D009419:Nerve Tissue Proteins; D057089:Pathology, Molecular; D017422:Sequence Analysis, DNA; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C552551:TBC1D24 protein, human; C482647:UBE3B protein, human; D044767:Ubiquitin-Protein Ligases