Robinow syndrome

Robinow syndrome is a rare disorder of skeletal development that affects many parts of the body. Researchers have identified two types of Robinow syndrome, which are distinguished by the severity of their signs and symptoms and by their patterns of inheritance.

Autosomal recessive Robinow syndrome is characterized by skeletal abnormalities including shortening of the long bones in the arms and legs, particularly the forearms; abnormally short fingers and toes (brachydactyly); wedge-shaped spinal bones (hemivertebrae) leading to an abnormal curvature of the spine (kyphoscoliosis); fused or missing ribs; and short stature. Affected individuals also have distinctive facial features, such as a broad forehead, prominent and widely spaced eyes, a short nose with an upturned tip, and a wide nasal bridge. Other common features of this disorder include underdeveloped genitalia and dental problems (such as crowded teeth and overgrowth of the gums). Kidney and heart defects are also possible. Delayed development occurs in 10 percent to 15 percent of people with this condition, although intelligence is usually normal.

The signs and symptoms of autosomal dominant Robinow syndrome are similar to, but tend to be milder than, those of the autosomal recessive form. Abnormalities of the spine and ribs are rarely seen in the autosomal dominant form.

Robinow syndrome is rare, with fewer than 200 affected people reported worldwide. The autosomal recessive form of this condition has been identified in families from several countries, including Turkey, Oman, Pakistan, and Brazil.

Mutations in the ROR2 gene cause autosomal recessive Robinow syndrome. This gene provides instructions for making a protein whose function is not well understood, although it is essential for normal development before birth. In particular, the ROR2 protein appears to play a critical role in the formation of the skeleton, heart, and genitals. Mutations in the ROR2 gene prevent cells from making any functional ROR2 protein, which disrupts embryonic development and leads to the characteristic features of Robinow syndrome.

The genetic cause of autosomal dominant Robinow syndrome is unknown. Abnormalities involving chromosome 1 have been reported in two people with the features of this condition. Further studies will help determine whether a gene associated with autosomal dominant Robinow syndrome is located on chromosome 1. Researchers suspect that mutations in a gene that works with ROR2 during early development may underlie this form of the disorder.

Read more about the ROR2 gene.

In some families, Robinow syndrome has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

In other families, Robinow syndrome has an autosomal dominant inheritance pattern. Autosomal dominant inheritance means one copy of an altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases occur in people with no history of the disorder in their family.