autosomal dominant Robinow syndrome 3

Autosomal dominant Robinow syndrome 3 is a genetic condition that primarily affects skeletal development and facial formation, leading to distinctive physical features recognizable from infancy. It is caused by pathogenic variants in the DVL3 gene, which encodes a protein involved in the Wnt signaling pathway that guides early growth and patterning. Both males and females can be affected, and signs are typically present at birth or early childhood. Exact frequency in the general population is not well established, but the condition is considered very uncommon. Severity and symptoms vary widely between individuals.

The condition affects multiple body systems and has a recognizable combination of craniofacial, skeletal, and genital findings. Craniofacial characteristics include a short nose with anteverted nares, a wide or depressed nasal bridge, midface retrusion, upslanted palpebral fissures, hypertelorism, and a long philtrum. A bifid tongue and gingival overgrowth are distinctive oral features, and some children have cleft palate or missing permanent teeth. Skeletal findings are central to diagnosis. Short stature with mesomelia (shortening of the middle portions of the limbs), brachydactyly, and clinodactyly are consistently reported. Some individuals have scoliosis or short finger bones identified on hand X-rays. Genital differences can include micropenis in males and clitoral hypoplasia in females. Cryptorchidism is common in affected boys. Variable features seen in a subset of individuals include epicanthal folds, proptosis, long eyelashes, a downturned mouth, and agenesis of permanent teeth. Not all individuals experience all features, and the clinical spectrum ranges from mild to more pronounced involvement.

Autosomal dominant Robinow syndrome 3 results from pathogenic variants in the DVL3 gene. DVL3 produces the dishevelled segment polarity protein 3, a key component of the Wnt signaling pathway that orchestrates cell growth and tissue patterning during embryonic development. When one copy of DVL3 carries a disease-causing change, the altered signaling disrupts normal skeletal and craniofacial formation, leading to the features described above. Because the condition follows an autosomal dominant inheritance pattern, a person with a DVL3 variant has a 50 percent chance of passing it to each child. Family members may show different symptom severity (variable expressivity), and in rare instances a parent carrying the variant may have minimal or subtle features. Genetic counseling is recommended for affected individuals and their relatives to clarify personal risks and discuss family-planning options.

Currently, management focuses on supportive care and symptom management tailored to each person’s needs. Long-term care is best coordinated by a multidisciplinary team that may include clinical geneticists, orthopedic surgeons, dentists, endocrinologists, and speech or feeding specialists. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Examples include periodic growth assessments, spinal monitoring for scoliosis progression, dental evaluations for gingival overgrowth or missing teeth, and urologic or reproductive assessments for genital concerns. Surgical procedures may be considered for cryptorchidism, cleft palate, or significant skeletal deformities, while physical and occupational therapy can maximize mobility and daily function. Patients should discuss management strategies with their healthcare team to determine which interventions are most appropriate for their specific situation, and genetic counseling can provide additional guidance for families.

Most individuals with autosomal dominant Robinow syndrome 3 have normal intelligence and life expectancy, although short stature and orthopedic issues can impact daily life and self-esteem. Outcomes depend on the severity of skeletal changes, presence of spinal curvature, and success of interventions for oral or genital anomalies. Access to coordinated specialist care and timely surgical or therapeutic interventions can greatly improve functional abilities and quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors for up-to-date information and support.