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

## TL;DR

A 12-month-old girl with a UBE3B gene variant is reported, adding to the understanding of Kaufman oculocerebrofacial syndrome and its clinical features.

## Contribution

This case report confirms the pathogenicity of a specific UBE3B splice site variant and expands the clinical description of Kaufman syndrome.

## Key findings

- A homozygous UBE3B splice site variant (c.1741 + 2T > C) was identified in a Jordanian girl with KOS.
- The variant was classified as pathogenic using ACMG/AMP criteria and previously reported in ClinVar.
- The case highlights the importance of considering KOS in infants with craniofacial features and developmental delay.

## Abstract

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.

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.

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.