Bannayan-Riley-Ruvalcaba syndrome (Bannayan syndrome)

Bannayan-Riley-Ruvalcaba syndrome (BRRS; Bannayan syndrome) is a rare genetic overgrowth disorder that forms part of the broader PTEN hamartoma tumour syndrome (PHTS) spectrum. It is caused by changes affecting the PTEN (phosphatase and tensin homolog) tumour-suppressor gene, which helps regulate cell growth. It is usually inherited in an autosomal dominant manner, although de novo variants also occur, so absence of a relevant family history does not exclude the diagnosis. A distinctive presentation may include macrocephaly, gastrointestinal polyposis, and pigmented macules of the penis.

It can present with psychiatric features such as autism spectrum disorder (ASD), ADHD, anxiety, depression, obsessive-compulsive symptoms (and OCD), and other behavioural or psychiatric difficulties. Psychotic disorders have also been reported. Neuropsychiatric manifestations can occur in childhood and adulthood.

From a morphologic lens perspective, other features include (but are not limited to):

• Macrocephaly

• Downslanted palpebral fissures

Other characteristic features include developmental delay or intellectual disability, seizures, hypotonia, and motor or speech delay. Other important manifestations include multiple gastrointestinal polyps, penile macules, lipomas, vascular malformations, thyroid abnormalities, and increased risk of several benign and malignant tumours.

Early diagnosis is important to identify neurodevelopmental and neurological manifestations; detect gastrointestinal polyps, vascular abnormalities, and other complications; and establish appropriate long-term surveillance for the increased risk of malignancy associated with PTEN hamartoma tumour syndrome.