Robinow syndrome
Robinow syndrome is a rare genetic disorder characterized primarily by skeletal abnormalities, distinctive facial features, and genital development issues.
Overview
Robinow syndrome is a rare disorder that affects the development of many parts of the body, particularly the skeleton. The condition is categorized by the severity of signs and symptoms and its pattern of inheritance: autosomal recessive or autosomal dominant.
Symptoms
Autosomal Recessive Robinow Syndrome
This form is characterized by skeletal abnormalities and distinctive facial features, sometimes described as "fetal facies" because they resemble the facial structure of a developing fetus.
- Shortening of the long bones in the arms and legs (particularly forearms)
- Brachydactyly (short fingers and toes)
- Wedge-shaped spinal bones (hemivertebrae) leading to abnormal curvature of the spine
- Fused or missing ribs
- Short stature
- Broad forehead, prominent eyes, a short nose with an upturned tip, a long philtrum, and a triangle-shaped mouth
- Underdeveloped genitalia
- Dental problems
- Possible kidney and heart defects
Autosomal Dominant Robinow Syndrome
Signs and symptoms are similar to the recessive form but tend to be milder. Abnormalities of the spine and ribs are rarely seen, and short stature is less pronounced. A variant form, the osteosclerotic form, includes increased bone mineral density (osteosclerosis) affecting the skull.
Causes
Autosomal recessive Robinow syndrome results from mutations in the ROR2 gene, which is essential for normal development of the skeleton, heart, and genitals. Autosomal dominant Robinow syndrome can be caused by mutations in several genes, including FZD2, WNT5A, DVL1, and DVL3. The osteosclerotic form results from DVL1 mutations.
Genes associated with Robinow syndrome
- DVL1
- DVL3
- FZD2
- ROR2
- WNT5A
- GPC4
- NXN
- RAC3
Inheritance
Robinow syndrome follows either an autosomal recessive or autosomal dominant pattern:
- Autosomal recessive: Both copies of the gene in each cell have mutations. Parents typically do not show signs of the condition.
- Autosomal dominant: One copy of an altered gene is sufficient to cause the disorder. Some cases are inherited from an affected parent, while others result from de novo (new) mutations in people with no family history of the disorder.