Year: 2026
Type: article
Study design: Case Report
Abstract: Johanson-Blizzard syndrome (JBS), also known as UBR1-related disorder, is a very rare autosomal recessive disorder caused by pathogenic variants in the UBR1 gene and characterized by significant phenotypic variability. The condition is known to be mainly characterized by craniofacial abnormalities, exocrine pancreatic insufficiency, growth retardation, and sensorineural hearing loss. We describe three affected siblings from a consanguineous Yemeni family with JBS. Two brothers suffered from profound symptoms resulting in infant death, which included failure to thrive, exocrine pancreatic dysfunction, anemia, hypoalbuminemia, aplasia cutis congenita, and cardiomyopathy, which was only present in one sibling. The third sibling, who is still alive, is a one-year-old girl who presented with vomiting, diarrhea, failure to thrive, and marked facial dysmorphic features, including hypoplastic alae nasi, a beaked nose, brachycephaly, and a fifth-finger anomaly, without significant visceral malformations. Genome analysis of the affected sibling revealed a homozygous missense mutation in the UBR1 gene, following the American College of Medical Genetics and Genomics (ACMG) guidelines. Moreover, the familial form, consanguinity, and typical presentation are highly suggestive of a diagnosis of JBS. The current case report draws attention to the significant variability of JBS within families and, once again, emphasizes the need for precise clinical assessment in order to make a diagnosis, especially when molecular testing might be equivocal in resource-poor environments. Early multidisciplinary supportive care and genetic counseling are pivotal for optimizing patient survival and minimizing the rate of recurrence within affected kindreds. A narrative review of the literature was conducted to contextualize the clinical findings and highlight intrafamilial phenotypic variability.
Source: Cureus
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7128921012