Please Remove Adblock
Adverts are the main source of Revenue for DoveMed. Please remove adblock to help us create the best medical content found on the Internet.

Robinow Syndrome

Last updated Jan. 14, 2019

Approved by: Krish Tangella MD, MBA, FCAP

Robinow Syndrome is a rare genetic disorder that affects approximately 1 in every 500,000 births.

What are the other Names for this Condition? (Also known as/Symptoms)

  • Acral Dysostosis with Facial and Genital Abnormalities
  • Fetal Face Syndrome
  • Robinow-Silverman-Smith Syndrome

What is Robinow Syndrome? (Definition/Background Information)

  • Robinow Syndrome is a rare genetic disorder that affects approximately 1 in every 500,000 births. It is caused by mutations in the ROR2, WNT5A, or DVL1 genes, which are required for early development of the fetus, especially of the fetal bones
  • The signs and symptoms of Robinow Syndrome include bone deformities in many regions of the body, including the face, arms, legs, spine and ribs. Additionally, congenital heart defects and genital abnormalities may be observed in the affected children
  • Due to the congenital heart defects observed in Robinow Syndrome, potential complications can include the narrowing of passages followed by laboured breathing. About 15% of the affected individuals have reported developmental delays associated with Robinow Syndrome
  • There are 2 forms of Robinow Syndrome. The autosomal recessive form tends to be more severe than the autosomal dominant variant. Having a family history of Robinow Syndrome is the single greatest risk factor for an infant to be born with this disorder
  • The diagnosis for Robinow Syndrome is generally made from a physical examination, where characteristic facial features may be noted. An evaluation of the family medical history, followed by genetic testing may aid in confirming the diagnosis. Radiological studies may also be required in order to detect bone deformations
  • The treatment for Robinow Syndrome is symptomatic in nature and generally requires a team of healthcare professionals in order for the affected child to lead as normal a life as possible. The prognosis is reportedly good; however, life expectancy may be shortened in individuals with severe congenital heart defects
  • Robinow Syndrome is a genetic disorder, and hence, there are currently no ways to prevent the syndrome from taking place. Expecting parents may benefit from genetic counselling and genetic testing of the developing fetal cells may be undertaken (to check for any abnormalities), if a family history of the condition exist

Who gets Robinow Syndrome? (Age and Sex Distribution)

  • Robinow Syndrome is a rare inherited disorder (either autosomal dominant or autosomal recessive). The prevalence of Robinow Syndrome is approximately 1 in every 500,000 births (study in the US)
    • The autosomal dominant form is reported in less than 50 families worldwide
    • The autosomal recessive form has been found in less than 200 families globally
  • Both genders are susceptible to the disorder; however, more males are generally diagnosed with Robinow Syndrome due to the distinct male genital abnormalities that are often associated with this condition (an easily identifiable feature)
  • Robinow Syndrome is reported to be prevalent in the United States, Arab countries, Turkey, Pakistan, and the Czech Republic. The prevalence in other regions of the world is not very well known

What are the Risk Factors for Robinow Syndrome? (Predisposing Factors)

Having a family history of Robinow Syndrome is the single major risk factor for this congenital disorder.

  • Nevertheless, if no family history of the condition is observed, Robinow Syndrome may still occur due to spontaneous mutations. The risk factors for such spontaneous mutations are currently unknown
  • Individuals originating from certain Arab countries, Turkey, Pakistan, Brazil, the Czech Republic, and the U.S. seem to be at a higher risk for developing the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Robinow Syndrome? (Etiology)

Robinow Syndrome is caused by genetic mutations in three genes. The gene that is affected dictates the type of inheritance of the disorder.

Autosomal recessive form of Robinow Syndrome (when both parents are carriers of the defective gene):

  • This form of Robinow Syndrome is caused by mutations in the ROR2 gene. This gene codes for the ROR2 protein. It belongs to a class of proteins known as receptor tyrosine kinases
  • Although the exact role of ROR2 protein is not well-characterized, it is believed to be involved in the cellular signalling pathways (a complex communication system of the cell) that are vital for proper fetal development
  • The lack of a functional ROR2 protein is believed to cause impaired development of the heart, skeleton, and the genitals during the fetal stages, which leads to the characteristic features of Robinow Syndrome

Autosomal dominant form (when a single parent is the carrier of the defective gene):

  • This form of Robinow Syndrome may be caused by mutations in the WNT5A or DVL1 genes. The WNT5A or DVL1 proteins coded by the WNT5A or DVL1 genes respectively are believed to be part of the ROR2 signaling pathway
  • If either protein is dysfunctional, the chemical signaling may be disrupted, which can lead to early developmental abnormalities in a fetus
  • In particular, DVL1 mutations are known to cause the osteosclerotic form of Robinow Syndrome, where the bones are thicker than usual. However, thicker bones do not mean stronger bones; the abnormally thick bones may in fact be more vulnerable to fractures in these children

Spontaneous mutations causing Robinow Syndrome:

  • There are some individuals with characteristic symptoms of Robinow Syndrome that do not have mutations in the ROR2, WNT5A or DVL1 gene
  • These individuals do not have a family history of the condition. In such cases, the exact cause of the condition is still being researched and characterized

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring. 

What are the Signs and Symptoms of Robinow Syndrome?

The signs and symptoms of Robinow Syndrome are determined by the specific variant (of inheritance) an individual has. While the symptoms are more severe in the autosomal recessive form, they tend to be milder in the autosomal dominant form. The signs and symptoms may be recognisable during infancy or early childhood.

Signs and symptoms of the autosomal recessive form:

  • Facial appearance: The facial features are collectively termed “fetal facies”, since they look similar to those of a fetus in development
    • Widely spaced eyes
    • Broad forehead
    • Broad nasal bridge
    • Upturned tip of nose
    • Mouth, shaped like a triangle
  • Short stature; short bones in the arms and legs and short fingers and toes (brachydcatyly)
  • Crowded teeth, overgrowth of the gums
  • Wedge-shaped bones in the spine (hemivertebrae); abnormally-curved spine (kyphoscoliosis)
  • Missing or fused ribs
  • Frequent ear infections, hearing difficulties
  • Respiratory problems such as breathing difficulties
  • Low muscle tone (hypotonia)
  • Feeding/eating difficulties
  • Genital abnormalities, such as a small penis (micropenis) and small testes, in males causing hypogonadism
  • Kidney defects and kidney malfunction resulting in decreased urine output
  • Congenital heart defects resulting in signs and symptoms of abnormally functioning heart
  • Inability to reach developmental milestones (occurs in about 10-15% of the babies)

Signs and symptoms of the autosomal dominant form: 

  • Characteristic facial features, such as seen in the autosomal recessive form, but is generally milder
  • Genital abnormalities, such as a small penis (micropenis) and small testes, in males causing hypogonadism
  • Umbilical hernia, wherein the intestine protrudes through the abdominal wall; typically through the belly button
  • Extra teeth in the mouth than normally observed; overgrowth of gums
  • Frequent ear infections, hearing difficulties
  • Respiratory problems
  • Low muscle tone (hypotonia)
  • Feeding/eating difficulties
  • Congenital heart defects resulting in signs and symptoms of abnormally functioning heart
  • Esophageal reflux
  • In some cases, osteosclerosis (in those with DLV1 mutation) may occur, which is increased mineral density of bones. In this condition, though the bones are thick, they are also weak, which can result in easy bone fractures

Note: The signs and symptoms associated with male genitalia are more prominent than those associated with female genitalia. Hence, Robinow Syndrome is more often diagnosed in males than females (easily recognizable).

How is Robinow Syndrome Diagnosed?

The diagnosis of Robinow Syndrome may be performed before and after birth. A diagnosis of Robinow Syndrome may be based on the following procedures:

  • Physical examination of the mother and child
  • Assessment of symptoms
  • Evaluation of family medical history
  • X-rays to detect or confirm bone abnormalities
  • Hormonal blood tests to detect the levels of male hormones (androgens), if the child has a small penis/testes (hypogonadism)
  • Ultrasound of the fetus to check for any morphological abnormalities
  • Genetic testing of fetal cells to check for mutation(s) characteristic of Robinow Syndrome

Clinical diagnosis: In some children, specific gene mutations may not be present in spite of having characteristic signs and symptoms. In such children, a diagnosis is made through analyzing the combination of signs and symptoms.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Robinow Syndrome?

The following are potential complications that may arise from Robinow Syndrome:

  • Obstruction of blood flow to the pulmonary artery (pulmonary stenosis) causing labored breathing, chest pain, and fatigue. This can lead to heart failure
  • Narrowing of passages or openings in the body (atresia). The children may have small nasal opening and/or small anus
  • Development of pneumonia in infants
  • Kidney abnormalities that can lead to chronic renal failure
  • Developmental delays in the child

How is Robinow Syndrome Treated?

There is no cure for Robinow Syndrome. The treatment for Robinow Syndrome is geared towards managing the signs and symptoms of the condition. Some available treatment measures include:

  • For skeletal malformations:
    • Bracing
    • Surgery
    • Physiotherapy
  • For dental issues:
    • Surgery
    • Braces
  • For genital abnormalities:
    • Surgery to correct cryptorchidism (undescended testis)
    • Surgery to correct other associated abnormalities such as small penis
  • Congenital heart defects: Once they are diagnosed, then appropriate treatment options (such as surgery) may be recommended
  • Developmental delays:
    • Growth hormone treatment to overcome short stature
    • Special education
    • Special social support
    • Vocational support
  • For gastrointestinal abnormalities including inguinal hernia and reflux disease, specific medications may be recommended

Caring for a child born with Robinow Syndrome may require a team of specialists from various fields working in cooperation in order to allow the child to have as normal a development as possible.

How can Robinow Syndrome be Prevented?

  • Currently, there are no specific methods or guidelines of prevention for Robinow Syndrome, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) followed by prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks prior to childrearing
  • Active research is currently being performed in order to explore both treatment and prevention methods for genetic disorders such as Robinow Syndrome

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Robinow Syndrome? (Outcomes/Resolutions)

  • The prognosis of Robinow Syndrome is reported to be generally good with appropriate treatment measures
  • The prognosis also depends on the severity of the signs and symptoms. Also, if congenital heart defects are severe, then life expectancy may be negatively affected

Additional and Relevant Useful Information for Robinow Syndrome:

Robinow Syndrome was formerly referred to as Costovertebral Segmentation Defect with Mesomelia, and Covesdem Syndrome.

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 10, 2016
Last updated: Jan. 14, 2019