BNAR syndrome

BNAR syndrome is a very rare congenital condition characterized by a bifid nose with a bulbous nasal tip and, in some cases, associated anorectal defects and renal anomalies. The syndrome is linked to pathogenic variants in the FREM1 gene and follows an autosomal recessive inheritance pattern. It is considered extremely rare, affecting fewer than 1 in one million people. Diagnosis and management typically occur in childhood when the characteristic facial and organ anomalies become apparent.

The hallmark feature of BNAR syndrome is a bifid nose, which is always present, giving rise to its distinctive facial appearance. Additional clinical features that may be observed include a short lingual frenulum, widely-spaced maxillary central incisors, thick eyebrows, and abnormalities of the ears such as low-set and posteriorly rotated ears with an overfolded helix. A subset of individuals may present with unilateral renal agenesis, Ebstein anomaly of the tricuspid valve, precocious puberty, and brachycephaly. Although the original description noted an absence of intellectual disability, some patients have been reported to show mild intellectual challenges. Not all individuals experience all features, and severity varies considerably.

BNAR syndrome is caused by pathogenic variants in the FREM1 gene, which plays a role in developmental processes. The condition is inherited in an autosomal recessive pattern, meaning an affected individual has received one altered copy of the gene from each parent. This condition is more common when parents share a common ancestor, as the likelihood that both carry the same rare variant increases. Genetic counseling is recommended for families to better understand the inheritance implications and recurrence risk.

Currently, management focuses on supportive care and symptom management as there are no specifically approved treatments for BNAR syndrome. Treatment is individualized and typically involves a multidisciplinary team that may include pediatric specialists, surgeons, and other experts as needed. Regular surveillance is an essential part of long-term care, helping to identify any emerging complications across the affected systems. Patients should discuss treatment options with their healthcare team and consider genetic counseling for further guidance.

The long-term outlook for BNAR syndrome is variable, with outcomes differing based on the severity and combination of the involved features. With current standards of care, many individuals are able to achieve a good quality of life and live into adulthood. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition to receive ongoing guidance and support.