skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome is a condition that affects multiple body systems, particularly impacting the skin, skeletal structure, and craniofacial features. It arises from alterations in the PDGFRB gene, which plays a role in cell growth and connective tissue development. The condition is inherited in an autosomal dominant manner, meaning a single pathogenic variant in PDGFRB can cause the syndrome. This condition is very rare, affecting fewer than 1 in 1 million people.

Individuals with this syndrome typically present with characteristic features such as fragile skin, a prominent forehead, overgrowth, and hyperextensible skin, all of which are reported in nearly all affected individuals. Other consistent findings include a thin upper lip vermilion, downslanted palpebral fissures, scoliosis, a wide nasal bridge, and proptosis. In addition, a subset of affected individuals may experience tall stature, thin skin, and xanthelasma, as well as neuropsychiatric features such as depression, anxiety, and intellectual disability. Not all individuals experience every symptom, and severity varies considerably.

The syndrome is caused by pathogenic variants in the PDGFRB gene. The PDGFRB gene encodes a receptor that is important in cell signaling and growth regulation, and alterations in its function can result in the diverse clinical features observed. Inheritance is autosomal dominant, which means that an affected individual has a 50% chance of passing the gene variant to each of their children. Because symptoms and severity can vary, even among family members, genetic counseling is recommended to help families understand the implications for future family planning.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved or specific foundational therapies for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary care team that may include dermatologists, orthopedic specialists, and mental health professionals. Regular surveillance is an essential part of long-term care, and patients are encouraged to monitor their condition through periodic follow-ups with their healthcare team. It is important for patients to consult their doctor to determine which therapies and monitoring strategies are most appropriate for their situation.

The course of skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome is highly variable, with outcomes depending on the severity of the symptoms and the timing of diagnosis. Although many individuals continue to experience the features from childhood into adulthood, improvements in supportive and multidisciplinary care have positively influenced the overall outlook. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to seek genetic counseling and connect with specialists for ongoing support.

There is active research in this area, and clinical trials are underway exploring new treatment approaches for this syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team for more information about eligibility and current research efforts.