autosomal recessive Robinow syndrome

Autosomal recessive Robinow syndrome is a skeletal dysplasia that affects bone growth, facial development, and the external genitalia. It is caused by pathogenic variants in the ROR2 gene, which plays a key role in signaling pathways that guide early skeletal formation. Signs of the condition are usually evident at birth or in early infancy and can affect individuals of any sex. Fewer than one in a million people worldwide are thought to have this form of Robinow syndrome, making it extremely uncommon. Because the condition follows an autosomal recessive inheritance pattern, both parents of an affected child are typically carriers of one altered copy of the gene.

The most consistent features include markedly short stature with disproportionately short limbs, very small fingernails and toenails, and distinctive hand changes such as fusion of the middle joints of the fifth fingers. Males are commonly born with a micropenis, while females may have underdeveloped external genitalia. Characteristic facial findings develop early and often include a wide nasal bridge, short up-turned nose, widely spaced eyes, and a mouth that appears wide with down-turned corners. The forehead may be prominent and the midface somewhat flattened, leading to a recognizable facial appearance. The skeleton is affected throughout the body. Many children have segmentation defects of the vertebrae, hemivertebrae, or fused ribs that can lead to scoliosis or a shortened trunk. Mesomelia, meaning shortening of the middle segments of the limbs, contributes to overall limb shortening. Hands and feet often show brachydactyly, clinodactyly, and short distal phalanges, resulting in broad, square palms. Dental crowding, an open bite, and other abnormalities of tooth shape are frequent and may require orthodontic attention. Additional findings vary. Some individuals develop chest wall asymmetry, while others remain relatively mild aside from short stature. Not all individuals experience all features, and severity varies considerably from one person to the next.

Autosomal recessive Robinow syndrome results from pathogenic variants in the ROR2 gene. The ROR2 protein is part of a receptor family that helps guide cell signaling during early bone and cartilage development; loss of normal function disrupts these pathways and leads to the skeletal and craniofacial differences observed. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered ROR2 gene from each parent to be affected. Parents who share a common ancestor are more likely to carry the same rare variant, so the condition may be observed more often in families where the parents are related. Carrier parents are typically healthy but have a 25% chance with each pregnancy of having an affected child, a 50% chance of having a carrier child, and a 25% chance of having a child who inherits neither altered copy. Even within the same family, the specific features and their severity can vary considerably (variable expressivity). Genetic counseling and carrier testing for at-risk relatives are strongly recommended.

There are currently no disease-specific approved treatments, so management focuses on supportive care tailored to the individual’s needs. Early in life, orthopedic specialists monitor limb and spine development, and surgical intervention may be considered for severe scoliosis or limb deformities. Dentists and orthodontists address dental crowding, open bite, and other oral issues, while endocrinologists monitor growth and pubertal development. Urologists or pediatric surgeons evaluate genital differences, particularly in males with micropenis. Regular surveillance is an essential part of long-term care, helping to identify potential complications such as progressive spinal curvature or respiratory restriction from rib fusion before they become serious. A multidisciplinary team—often including orthopedic surgeons, geneticists, dentists, endocrinologists, and physical therapists—coordinates care, supports mobility, and optimizes quality of life. Families should discuss individualized monitoring schedules and therapy options with their healthcare team and consider genetic counseling when planning future pregnancies.

Life expectancy is generally thought to be near normal, although long-term data are limited because the condition is so rare. Short stature and skeletal differences are lifelong, and some individuals may require orthopedic surgery or respiratory support if spinal or rib abnormalities progress. Overall outcomes depend on the severity of skeletal involvement, early recognition of spine and airway complications, and access to specialized care. Severity and symptoms vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialist centers familiar with Robinow syndrome for ongoing guidance and support.