Proteus syndrome

Proteus syndrome is a very rare and complex hamartomatous overgrowth disorder marked by progressive enlargement affecting the skeleton, skin, adipose tissue, and central nervous system. The condition is associated with a mosaic alteration in the AKT1 gene, which occurs sporadically rather than being inherited. It typically presents in early childhood with distinctive features that evolve over time. As it affects fewer than 1 in 1,000,000 people, diagnosis and management are tailored to the individual based on the specific clinical presentation.

A key characteristic of Proteus syndrome is the presence of a cerebriform connective tissue nevus, which is observed in all affected individuals. Other features may include progressive overgrowth of various tissues, with the severity and combination of manifestations varying considerably from person to person. While the overgrowth can affect multiple systems, the clinical presentation is highly variable and not everyone will experience additional complications beyond the hallmark skin finding. Not all individuals experience all features, and severity varies considerably.

Proteus syndrome is caused by a mutation in the AKT1 gene that occurs as a sporadic event early in development. This mutation is not inherited from the parents, and the condition is considered multifactorial owing to its complex presentation. As a result of the mutation, abnormal cellular growth and differentiation occur, leading to the progressive overgrowth seen in affected individuals. Families are encouraged to seek genetic counseling to better understand the nature of this sporadic condition and its implications for family planning.

Currently, management focuses on supportive care and symptom management, as no treatments have been specifically approved for Proteus syndrome. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include specialists in genetics, orthopedics, dermatology, and other fields as needed. Regular monitoring is important to address evolving complications, and patients are encouraged to discuss treatment options with their healthcare team to determine the most appropriate interventions for their situation.

The course of Proteus syndrome is highly variable, with outcomes that can differ substantially among affected individuals. With current standards of care, many individuals experience a period of stability after the initial manifestation of symptoms, although some may face progressive challenges over time. Outcomes described in medical literature continue to evolve as standards of care improve, and it is important to recognize that severity and symptoms vary widely between individuals. Families often find it helpful to connect with genetic counselors and specialist centers to better understand the potential trajectory and to navigate ongoing care.

Clinical trials are underway exploring new treatment approaches for Proteus syndrome. Although no therapies have been approved specifically for this condition, several investigational therapies are being evaluated to address the complex symptoms associated with the disorder. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.