autosomal dominant Robinow syndrome 1

Autosomal dominant Robinow syndrome 1 is a skeletal dysplasia that primarily affects bone growth and facial development. The condition is caused by changes in the WNT5A gene, which plays an important role in signaling pathways that guide early embryonic patterning and limb formation. Features are usually recognized in infancy or early childhood, although some milder cases may not be diagnosed until later. Precise prevalence figures are not available, but the condition is considered very uncommon. Severity and symptoms vary widely between individuals.

The most consistent findings include shortened fingers and toes (brachydactyly), a characteristically short nose, and proportionately short stature. These traits are often present at birth and typically prompt the initial evaluation. As children grow, additional skeletal differences can emerge, such as shortened long bones of the arms and legs and limited elbow movement due to a dislocated radial head. Craniofacial features help clinicians recognize the syndrome. Many individuals have a flat or depressed nasal bridge, a long space between the nose and upper lip (long philtrum), hypertelorism with proptosis, and downslanted eyelid openings. Low set or posteriorly rotated ears, malar flattening, and micrognathia are reported in a sizeable proportion of affected people. Dentition and other extraskeletal issues may develop over time. Persistence of primary teeth, gingival overgrowth, and a short lingual frenulum can affect feeding and speech. Some children have sacral dimples or wide anterior fontanels noted in infancy. Not all individuals experience all features, and the clinical spectrum ranges from mild to more complex presentations.

Autosomal dominant Robinow syndrome 1 results from pathogenic variants in the WNT5A gene. WNT5A encodes a signaling protein that influences how cells communicate during early development, especially in structures that give rise to the skeleton and facial tissues. When one copy of the gene is altered, the disrupted signaling leads to the skeletal and craniofacial findings characteristic of the condition. The disorder follows an autosomal dominant inheritance pattern, meaning a single altered copy is enough to cause the syndrome. An affected person has a 50 percent chance of passing the variant to each child. Even within the same family, the severity and specific symptoms can vary considerably, a phenomenon known as variable expressivity. Because the condition is inherited, genetic counseling is recommended for families to understand recurrence risks and reproductive options.

Currently, management focuses on supportive care and symptom management. Treatment is tailored to each person and typically involves a multidisciplinary team that may include orthopedists, dentists, speech therapists, and genetic specialists. Long-term management includes regular surveillance for potential complications. Orthopedic monitoring helps address joint limitations or progressive limb differences, and routine dental evaluations manage persistent primary teeth and gingival overgrowth. There are no gene-specific therapies at this time, so interventions aim to optimize growth, mobility, and quality of life. Physical and occupational therapy can improve range of motion and functional skills, while surgical procedures are considered for significant skeletal or dental issues. Patients should discuss treatment options and individualized monitoring schedules with their healthcare team to determine what is appropriate for their situation.

Most individuals with autosomal dominant Robinow syndrome 1 lead full lives, although short stature and orthopedic challenges can affect daily activities. Intellectual development is typically normal, and life span is not thought to be significantly shortened, but outcomes depend on symptom severity, early recognition, and access to specialized care. Variability remains high, even among affected relatives. 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 who can coordinate care and provide up-to-date guidance.