Robinow syndrome encompasses two different hereditary disorders, both rare, with a similar pattern of physical abnormalities. Typical features of these conditions include mild to moderate short stature, distinctive facial features, skeletal abnormalities, and abnormal development of the genitalia.
A family that included several individuals with a characteristic pattern of facial features, accompanied by short stature (dwarfism), skeletal abnormalities, and underdevelopment (hypoplasia) of the external genitalia (sex organs) was first described in 1969 by Dr. Meinhard Robinow. He named the condition "Fetal face syndrome," because the facial features are similar to those of a normal fetus. Only later was Dr. Robinow's name used to identify the syndrome. Other names for the condition include Robinow dwarfism, as well as "acral dysostosis with facial and genital abnormalities."
Skeletal abnormalities of varying types and severity occur in every case of Robinow syndrome. Most people with the condition have abnormal development of specific bones of the arms and legs resulting in some degree of short stature. Spinal abnormalities are also common. Most females are fertile, but only a few males with the condition have had children.
Chromosomes are the microscopic structures inside cells that carry the genes. Each cell of the body contains 46 chromosomes in 23 pairs. The exceptions are sperm and eggs, which normally carry 23 chromosomes—one of each pair. The first 22 pairs of chromosomes in humans are known as the autosomes. An inherited condition is autosomal if the abnormal gene that causes it resides on one of the first 22 pairs of chromosomes.
Several years after Dr. Robinow's first report, it became clear that some families affected by Robinow syndrome have an autosomal dominant pattern of inheritance, while in other families the syndrome is inherited as an autosomal recessive trait. The reason for this genetic discrepancy is unknown.
Dominant inheritance means that an error in only one gene of a pair is enough to produce symptoms of the disorder. In other words, the abnormally functioning gene of the pair is dominant over the normal gene. A person who carries the gene for autosomal dominant Robinow syndrome has a 50% chance of passing it on to each of his or her offspring.
In autosomal recessive inheritance, a person must have errors in both copies of a gene pair in order to be affected. Someone who carries just one copy of the disease gene has another normally functioning gene of that pair to compensate for it. Therefore, a carrier of a single recessive gene typically shows no symptoms of the disorder. If two people who both carry the gene for recessive Robinow syndrome conceive a pregnancy, there is a 25% chance that they will each contribute the Robinow syndrome gene and have an affected child.
Mutations in the ROR2 gene are responsible for recessive Robinow syndrome. The exact function of the protein encoded by the ROR2 gene has not been determined, and the gene responsible for dominant Robinow syndrome has not been located.
Both the dominant and recessive forms of Robinow syndrome are rare. Dominant Robinow syndrome does not appear to occur more frequently in any particular ethnic group. A significant proportion of recessive Robinow syndrome cases, however, have occurred in Czechoslovakia, Turkey, and the Middle East. In addition, some children with recessive Robinow syndrome have parents who are genetically related (consanguineous), such as first cousins. Parental consanguinity is sometimes seen in rare, autosomal recessive conditions, since people who are genetically related are more likely to carry the same recessive gene(s).
Signs and symptoms
The signs and symptoms of Robinow syndrome can be grouped into those that involve the face, those that affect the skeleton, and those affecting the genitalia. There is a good deal of overlap of symptoms between the dominant and recessive forms. In general, however, people with recessive Robinow syndrome tend to be more severely affected.
wide space between the eyes (hypertelorism), wide eye openings, low-set ears, long philtrum (groove from nose to upper lip), small lower jaw (micrognathia), excessive growth of the gums, and crowding of teeth.
People with Robinow syndrome have what is known as acromesomelic brachymelia. Acromesomelic refers to bones at the end (acro) and in the middle (meso) of the limbs. Brachymelia is the medical term for short limbs. Thus, short limbs in Robinow syndrome are due to shortened bones in the hands, feet, lower arms, and lower legs. Dominant Robinow syndrome is associated with normal height to borderline short stature, while recessive Robinow syndrome always results in short stature. Abnormalities of the spine often involve misshapen or fused vertebrae (so-called segmentation defects), as well as scoliosis. Vertebral abnormalities are more frequent and more pronounced in the recessive form of Robinow syndrome. Ribs may be fused together or abnormally shaped, and this may lead to pectus excavatum (sunken breastbone).
Males with Robinow syndrome typically have a hypoplastic penis, and may have undescended testicles (cryptorchidism). Females can have a small clitoris and hypoplastic labia. A dysfunctional sex-steroid response-and-feedback mechanism may be partly to blame for some of the signs of Robinow syndrome, particularly the genital anomalies.
Physical anomalies found less frequently in Robinow syndrome include heart defects, kidney abnormalities, cleft lip/palate, and hearing loss. Most individuals with Robinow syndrome have normal intelligence, but a few have mild mental retardation.
The diagnosis of Robinow syndrome is made by physical examination. Several other genetic syndromes have some of the same physical signs as Robinow syndrome, which can make arriving at the correct diagnosis more difficult. However, the pattern of skeletal abnormalities in Robinow syndrome has a distinct appearance when seen on x rays, which may help in confirming the diagnosis. Testing of the ROR2 gene is theoretically possible for recessive Robinow syndrome, but would only be offered on a research basis, if at all. There are no laboratory tests available to aid in the diagnosis of dominant Robinow syndrome.
Treatment and management
There is no cure for either type of Robinow syndrome. Future research may help to determine if some type of hormone therapy can be used to treat the short stature and/or hypoplastic genitalia. Otherwise, no specific protocol is recommended for managing children and adults with either form of the condition. An orthopedic surgeon might be needed to address any problems that arise related to skeletal abnormalities, especially in the spine. Special educational intervention would be indicated for anyone with learning disabilities or mental retardation.
People with pronounced physical signs of the condition (short stature and facial features) may have difficulties with their self-image. Males with a hypoplastic penis can present a special problem. In those cases, added psychological and social support is particularly important. Genetic counseling should be offered to individuals/families affected by Robinow syndrome to help them understand the condition, its inheritance, and any testing (including prenatal) that might be available.
Any one person with Robinow syndrome may have a good prognosis, depending on how well they cope with their particular symptoms. A child with recessive Robinow syndrome is more likely to have long-term difficulties than a child with the dominant form of the condition, but no blanket statements can be made. Overall, life span should not be significantly decreased in most cases of Robinow syndrome, since the majority of affected individuals do not have life-threatening complications.
Jones, Kenneth Lyons. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia: W.B. Saunders Company, 1997.
Robinow Syndrome Foundation. PO Box 1072, Anoka, MN 55303. (612) 434-1152. <http://www.robinow.org>.
"Robinow syndrome." National Library of Medicine (NLM). MedlinePlus. <http://medlineplus.nlm.nih.gov/mesh/jablonski/syndromes/syndrome_cgi?index=562.htm>.
Scott J. Polzin, MS