Borjeson-Forssman-Lehman syndrome (BFLS) is a rare X-linked genetic disorder characterized by a variety of symptoms, including seizures, intellectual disability, obesity, developmental delay, and distinctive facial appearance. It is caused by mutations in the PHF6 gene located on the X-chromosome, and the primary clinical symptoms vary within and between families.
The history of BFLS dates back six decades when Börjeson, Forssman, and Lehman first identified the syndrome in three males with significant intellectual disability, developmental delay, obesity, hypogonadism, and hypometabolism. Other symptoms included narrow palpebral fissures, thickening of subcutaneous tissue of the face, big ears, dwarfism, and moderate mental retardation in carrier females.
Subsequent studies expanded upon these observations and revealed that the phenotypic characteristics of BFLS are milder and more diverse than initially thought. Newborns with BFLS may exhibit floppy muscles, poor growth, small external genitalia, and large ears. As they grow older, developmental delays, learning difficulties, truncal obesity, and gynecomastia become more prominent. Facial features also become coarser in late adolescence and adulthood.
BFLS is primarily caused by mutations in the PHF6 gene, which is expressed during the early stages of central nervous system development. This gene is involved in transcriptional control and plays a role in regulating gene expression.
Diagnosing BFLS is typically based on a clinical evaluation, medical history, and physical examination, with confirmation through genetic testing. There is no specific cure for BFLS, but treatment focuses on managing individual symptoms and providing early developmental intervention.
Despite being a relatively rare condition, BFLS affects both males and females. However, the phenotypic expression in females is highly varied and can be difficult to predict. The exact incidence of BFLS is unknown, but it may be underestimated due to the identification of isolated affected females.
Further research and genetic counseling are essential for a better understanding of BFLS and to provide appropriate support to affected individuals and their families.
Sources:
– Bellad A, Bandari AK, Pandey A, et al. (2020). A Novel Missense Variant in PHF6 Gene Causing Börjeson-Forssman-Lehman Syndrome.
– Zhang X, Fan Y, Liu X, et al. (2019). A Novel Nonsense Mutation of PHF6 in a Female with Extended Phenotypes of Borjeson-Forssman-Lehmann Syndrome.
– Kasper BS, Dörfler A, Di Donato N, et al. (2017). Central nervous system anomalies in two females with Borjeson-Forssman-Lehmann syndrome.
– Jahani-Asl A, Cheng C, Zhang C, et al. (2016). Pathogenesis of Börjeson-Forssman-Lehmann syndrome: Insights from PHF6 function.
– Gécz J, Turner G, Nelson J, et al. (2006). The Börjeson-Forssman-Lehman syndrome (BFLS, MIM #301900).
– NIH-GARD. Borjeson-Forssman-Lehmann syndrome.
– OMIM. BORJESON-FORSSMAN-LEHMANN SYNDROME; BFLS.
– National organization for Rare Disorders. Börjeson-Forssman-Lehman Syndrome.
