Robinow syndrome is a rare genetic condition affecting bone and other body tissues. It occurs in approximately 1 in 500,000 individuals. The disorder is sometimes called fetal face syndrome because the facial features can resemble a developing fetus. The signs and symptoms vary significantly among affected individuals.
Physical Characteristics and Associated Health Conditions
The most recognizable signs involve the head and face. This includes a large head (macrocephaly) with a prominent forehead. The eyes are widely spaced (hypertelorism), and a short, upturned nose with a broad bridge is common. Other facial characteristics include a long groove in the center of the upper lip and low-set or rotated ears.
Skeletal development is significantly affected, leading to short stature. A defining feature is mesomelic limb shortening, where the forearms and lower legs are disproportionately short. The fingers and toes are also commonly short (brachydactyly). Spinal abnormalities are frequent, particularly in the more severe form, and can include wedge-shaped vertebrae (hemivertebrae) that lead to scoliosis, a sideways curvature of the spine.
Beyond the skeleton, Robinow syndrome can involve other body systems. Dental problems are common, including crowded teeth, delayed eruption of permanent teeth, and overgrown gum tissue. Underdevelopment of the external genitalia is a defining feature. In males, this can present as a small penis (micropenis), while females may have a small clitoris and labia majora.
Congenital heart defects are found in some individuals and represent a major cause of morbidity. Other potential health issues include frequent ear infections, hearing loss, and respiratory problems. While developmental delays can occur, intellectual development is within the normal range for most individuals.
Genetic Origins and Inheritance Patterns
Robinow syndrome is caused by mutations in genes that play a part in the body’s developmental processes. The condition is inherited in two distinct patterns, autosomal recessive or autosomal dominant, which correlate with symptom severity. The implicated genes are involved in the Wnt signaling pathway, which directs embryonic development.
The autosomal recessive form is the more severe type. An individual must inherit one mutated copy of a specific gene from each parent. The primary gene associated with this form is ROR2. Mutations in this gene disrupt its function, leading to more pronounced skeletal issues like vertebral segmentation defects and fused or missing ribs.
The autosomal dominant form is milder, and a person only needs to inherit one mutated gene from one parent. Several genes have been linked to this form, including WNT5A, DVL1, and FZD2. Individuals with the dominant form have the characteristic facial and genital features but fewer, if any, spinal and rib anomalies.
The Diagnostic Process
Diagnosis of Robinow syndrome often begins with a clinical evaluation after birth. A clinical geneticist or pediatrician performs a physical examination, looking for the recognizable pattern of physical traits. The combination of characteristic facial features, limb shortening, and genital abnormalities raises suspicion for the syndrome.
Radiological studies are used to assess the extent of the condition. X-rays are necessary to identify and evaluate specific skeletal malformations, confirming the presence of mesomelic shortening, brachydactyly, and vertebral anomalies. Prenatal diagnosis is sometimes possible through fetal ultrasound, which can detect limb length discrepancies.
Molecular genetic testing provides definitive confirmation. This testing analyzes a blood, saliva, or skin sample for mutations in the genes known to cause the disorder. Identifying a pathogenic variant in genes such as ROR2, WNT5A, or DVL1 confirms the diagnosis and clarifies the specific type, which helps guide management.
Management and Lifelong Care
There is no cure for Robinow syndrome; medical care focuses on managing specific symptoms and health issues. This requires a coordinated, multidisciplinary team of specialists to monitor for complications and intervene when necessary.
Surgical interventions are often required to correct structural abnormalities. Orthopedic surgeons may perform procedures to address severe scoliosis, and plastic surgeons might correct a cleft palate. For males with certain genital anomalies or undescended testes, corrective surgery may be recommended, while cardiologists manage any congenital heart defects.
Ongoing monitoring by various specialists is part of lifelong care. Regular appointments with an orthopedist track skeletal development, and a cardiologist monitors heart function. Routine visits to a dentist and orthodontist are necessary to address common dental issues. Hormone therapy may be considered in certain cases.
Physical and occupational therapy can help address delays in motor skills and improve physical functioning. Regular developmental assessments throughout childhood ensure that any learning or cognitive delays are identified and addressed early. This comprehensive approach allows for proactive management of the health challenges associated with the syndrome.