Kaufman oculocerebrofacial syndrome - case report of a UBE3B splice site variant and clinical overview of reported patients

Sep 29, 2026

Kaufman oculocerebrofacial syndrome (KOS) is a rare autosomal recessive disorder caused by pathogenic biallelic UBE3B variants, presenting craniofacial dysmorphism, global developmental delay, hypotonia, and multisystem anomalies. The report describes a 12-month-old Jordanian girl with microcephaly, hypotonia, feeding difficulties, and failure to thrive, plus mild basal septal hypertrophy. Whole-exome sequencing identified a homozygous UBE3B splice-site variant c.1741+2T>C. Family history suggested additional neonatal deaths, supporting an autosomal recessive condition. The case expands limited KOS literature and reinforces the variant’s pathogenicity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages4

Reading Time10 min

AccessFree to download

Abstract

Background

Case presentation

Conclusion

Background

Case presentation

Abdelfattah and Saleh Molecular Cytogenetics (2026) 19:1 Molecular Cytogenetics [https://doi.org/10.1186/s13039-025-00742-3](https://doi.org/10.1186/s13039-025-00742-3) CASE REPORT Open Access Kaufman oculocerebrofacial syndrome: case report of a UBE3B splice site variant and clinical overview of reported patients Abedul rhman S. Abdelfattah 1 and Mohammad Abu Saleh2* Abstract Background Kaufman oculocerebrofacial syndrome (KOS; OMIM \#244450)is a rare autosomal recessive disorder caused by pathogenic biallelic variants in UBE3B, characterized by craniofacial dysmorphism, global developmental delay, hypotonia, and multisystem anomalies. Case presentation We describe a 12-month-old Jordanian girl born to consanguineous parents, who exhibited microcephaly, hypotonia, feeding difficulties, and failure to thrive. Echocardiography revealed a mild basal septal hypertrophy. Developmental evaluation confirmed moderate global delay. Whole-exome sequencing revealed a homozygous UBE3B splice site variant (c.1741 + 2T >C), previously reported as pathogenic in ClinVar and classified as pathogenic according to ACMG/AMP criteria but without a detailed phenotypic description. Family history revealed additional neonatal deaths in a consanguineous context, raising the possibility of an underlying autosomal recessive condition. Conclusion This case adds to the limited body of literature on KOS and provides further evidence for the pathogenicity of the c.1741 + 2T >C variant. This case highlights the importance of considering KOS in infants presenting with characteristic craniofacial features such as blepharophimosis, ptosis, preauricular tags, and developmental delay, particularly in consanguineous families. Keywords Kaufman oculocerebrofacial syndrome, UBE3B gene, Developmental delay, Dysmorphic features, Whole exome sequencing. Background Kaufman oculocerebrofacial syndrome (KOS) (OMIM \#244450) is a very rare autosomal recessive disorder caused by pathogenic biallelic variants in the UBE3B gene. KOS is a multisystem disorder characterized not only by distinctive craniofacial features and global *Correspondence: Mohammad Abu Saleh [mohammad.abusaleh025@gmail.com](mohammad.abusaleh025@gmail.com) 1Department of Pediatrics, Faculty of Medicine, The Hashemite University, Zarqa, Jordan 2Faculty of Medicine, The Hashemite University, Zarqa, Jordan developmental delay, but also by hypotonia, feeding difficulties, growth deficiency, and involvement of multiple organ systems, including the neurologic, ophthalmologic, cardiac, skeletal, and renal systems. Facial features typically include blepharophimosis, ptosis, hypertelorism, short palpebral fissures, low-set ears with preauricular tags, micrognathia, and microcephaly. Kaufman et al. first described four siblings with a consistent constellation of craniofacial, neurologic, and developmental features in 1971, suggesting an autosomal recessive syndrome. The condition was later named Kaufman oculocerebrofacial syndrome (KOS), and in © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. Abdelfattah and Saleh Molecular Cytogenetics

FAQs

What causes Kaufman oculocerebrofacial syndrome (KOS)?

KOS is caused by pathogenic biallelic variants in the UBE3B gene, leading to characteristic craniofacial, neurologic, and multisystem features.

What genetic variant was identified in the reported patient?

Whole-exome sequencing found a homozygous UBE3B splice site variant: c.1741 + 2T > C.

Why is the case important for clinical practice?

It adds to limited KOS literature and supports the pathogenicity of the identified variant, helping clinicians consider KOS in infants with characteristic craniofacial features and developmental delay, especially in consanguineous families.

Sep 29, 2026

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