autosomal dominant Robinow syndrome 2

Autosomal dominant Robinow syndrome 2 is a multi-system developmental condition that chiefly affects skeletal growth and craniofacial formation. It is caused by pathogenic variants in the DVL1 gene, which plays an important role in cellular signaling pathways that guide normal embryonic development. Signs are usually noticeable in infancy or early childhood and can involve the bones, facial features, and neurodevelopment. Precise prevalence figures have not been established, but the condition is considered uncommon, with only several dozen families described in the medical literature. Both males and females can be affected, and the clinical picture can range from mild to more pronounced involvement.

The most recognizable features involve the face and skull. Many children have a depressed and wide nasal bridge, frontal bossing that gives the forehead a prominent appearance, a broad mouth that can appear triangular, thick upper lips, and a short upturned nose. Midface retrusion together with high palate and low-set ears further contribute to the distinctive facial profile. Skeletal findings are also characteristic. Hip dislocation or limited hip extension may be detected early, and shortening or curving of the fingers (brachydactyly and clinodactyly) is common. Some individuals have hypoplasia of the radius and areas of increased bone density in the skull (calvarial osteosclerosis). Macrocephaly is frequently reported. Neurologically, a thin corpus callosum and global developmental delay indicate that brain structure and function can be involved. Developmental delays may affect motor, language, and cognitive milestones, and tailored educational and therapeutic support is often needed. Mixed hearing impairment can further influence speech development, so early audiologic evaluation is important. In males, micropenis has been described. Oligodontia, or congenitally missing teeth, may complicate feeding and dental health. Other less constant features such as anteverted nares or a very long philtrum may appear in a subset of individuals. Not all individuals experience all features, and severity varies considerably, even within the same family.

Autosomal dominant Robinow syndrome 2 results from changes in a single copy of the DVL1 gene. DVL1 encodes the dishevelled segment polarity protein 1, a key component of the Wnt signaling pathway that coordinates tissue patterning during embryonic growth. When one copy of the gene is altered, signaling is disrupted, leading to the distinctive skeletal, craniofacial, and developmental findings described above. The condition follows an autosomal dominant inheritance pattern, meaning an affected individual has a 50 percent chance of passing the pathogenic variant to each child. While most people who inherit the variant develop symptoms, the specific features and their severity can differ markedly among relatives, a phenomenon known as variable expressivity. Genetic counseling is strongly recommended for families to understand their individual risks and reproductive options.

Currently, management focuses on supportive care and symptom-directed interventions. Orthopedic evaluation is important for hip dislocation or limited joint mobility, and some individuals may benefit from surgical correction or physical therapy to improve range of motion. Regular dental care is required for oligodontia and high palate, while hearing aids or other audiologic interventions can address mixed hearing loss. Developmental and educational therapies, including physical, occupational, and speech therapy, help children achieve their best functional outcomes. Because multiple organ systems can be affected, coordination by a multidisciplinary team that may include orthopedic surgeons, medical geneticists, developmental specialists, audiologists, and dentists is recommended. Regular surveillance for orthopedic complications, growth, and developmental progress allows emerging issues to be addressed promptly. Families should discuss individualized care plans and long-term monitoring schedules with their healthcare providers.

Long-term outlook depends on the combination and severity of skeletal, developmental, and medical issues present in each individual. Many people achieve good overall health and can participate in typical daily activities with appropriate medical and educational support, while others may need more intensive interventions. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialist teams familiar with Robinow spectrum disorders and to seek ongoing genetic counseling for future planning.