Tatton-Brown-Rahman overgrowth syndrome

Tatton-Brown-Rahman overgrowth syndrome is a rare disorder characterized by overgrowth, distinctive facial features, and mild to moderate intellectual disability. Caused by changes in the DNMT3A gene, this condition affects multiple systems including the central nervous system and skeletal development. It is inherited in an autosomal dominant pattern and is recognized for its characteristic facial dysmorphism and neurodevelopmental challenges. In plain terms, it affects fewer than 1 in 1,000,000 people.

Individuals with Tatton-Brown-Rahman overgrowth syndrome typically present with a constellation of features. The characteristic findings include a round face, heavy horizontal eyebrows, and narrow palpebral fissures along with an exaggerated cupid's bow, everted upper lip vermilion, deep philtrum, and anteverted nares. Additional consistent features are overgrowth, intellectual disability, global developmental delay, and hypotonia; many also experience congenital heart defects such as ventricular septal defect and other anomalies including Chiari type I malformation and talipes valgus. Not all individuals experience all features, and severity varies considerably, with some developing scoliosis, macrocephaly, or even febrile seizures during early childhood.

Tatton-Brown-Rahman overgrowth syndrome is caused by pathogenic variants in the DNMT3A gene, a gene important for regulating DNA methylation and normal development. The condition follows an autosomal dominant inheritance pattern, meaning that a single copy of the altered gene can result in the disorder. As with many autosomal dominant conditions, there can be variable expressivity, with affected individuals showing a range of symptom severity. Families are encouraged to seek genetic counseling to discuss inheritance implications and options for family planning.

Currently, management focuses on supportive care and symptom management, as no treatments are specifically approved for Tatton-Brown-Rahman overgrowth syndrome. Treatment is tailored to the individual and typically involves a multidisciplinary team to address the various aspects of the condition. Regular surveillance is an essential part of long-term care, helping to identify potential complications—in particular, monitoring developmental progress, cardiac function, and musculoskeletal issues. Patients and families are encouraged to discuss treatment options with their healthcare team and consider genetic counseling for further guidance.

Outcomes for individuals with Tatton-Brown-Rahman overgrowth syndrome vary depending on the severity of symptoms and access to specialized care. With current standards of care, many individuals achieve a good quality of life, although they may face challenges related to intellectual disability and other congenital anomalies. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists experienced in managing this condition. Overall, the course of the syndrome is variable, with some individuals experiencing a relatively stable developmental trajectory while others may require ongoing interventions.