Johanson-Blizzard syndrome

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive multisystem disorder caused by mutations in the UBR1 gene, which encodes a ubiquitin ligase involved in protein degradation. The condition is typically recognized at birth due to its characteristic features, which include aplasia or hypoplasia of the nasal alae (underdeveloped or absent nasal wings), giving the nose a distinctive beak-like appearance. Other hallmark features include exocrine pancreatic insufficiency leading to malabsorption and failure to thrive, congenital scalp defects (aplasia cutis congenita), and abnormalities of the permanent teeth (oligodontia or absence of permanent teeth). Many affected individuals also have sensorineural hearing loss, which can range from mild to profound. Additional features may include hypothyroidism, genitourinary malformations (such as imperforate anus, rectovaginal fistula, or ambiguous genitalia), short stature, and variable degrees of intellectual disability, though some individuals have normal cognitive function. Cardiac defects and midline anomalies such as absent or malformed nasal septum may also occur. The pancreatic insufficiency results from replacement of the exocrine pancreas with fatty tissue, while the endocrine function is usually preserved, though diabetes mellitus may develop later in life. Treatment is supportive and multidisciplinary. Pancreatic enzyme replacement therapy is essential for managing malabsorption and improving nutritional status. Hearing aids or cochlear implants may be needed for hearing loss, and thyroid hormone replacement is given when hypothyroidism is present. Surgical interventions may be required for craniofacial, genitourinary, or anorectal anomalies. Dental prosthetics and orthodontic care address the dental abnormalities. With appropriate management, survival into adulthood is possible, though outcomes depend on the severity of the associated malformations and complications.

Common questions about Johanson-Blizzard syndrome