Robinow syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Robinow syndrome is a rare disorder that affects the development of many parts of the body, particularly the skeleton. The types of Robinow syndrome can be distinguished by the severity of their signs and symptoms and by their pattern of inheritance: autosomal recessive or autosomal dominant.

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, a wide nasal bridge, and a broad and triangle-shaped mouth. Together, these facial features are sometimes described as "fetal facies" because they resemble the facial structure of a developing fetus. Other common features of autosomal recessive Robinow syndrome include underdeveloped genitalia in both males and females, and dental problems such as crowded teeth and overgrowth of the gums. Kidney and heart defects are also possible. Development is delayed in 10 to 15 percent of people with this condition, although intelligence is usually normal.

Autosomal dominant Robinow syndrome has signs and symptoms that 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, and short stature is less pronounced. A variant form of autosomal dominant Robinow syndrome includes increased bone mineral density (osteosclerosis) affecting the bones of the skull in addition to the signs and symptoms listed above. This variant is called the osteosclerotic form of Robinow syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive Robinow syndrome results from mutations in the ROR2 gene. This gene provides instructions for making a protein whose function is not well understood, although it is involved in chemical signaling pathways that are 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 development starting before birth and leads to the characteristic features of Robinow syndrome.

Autosomal dominant Robinow syndrome can be caused by mutations in several genes, including FZD2, WNT5A, DVL1, and DVL3. The osteosclerotic form of the condition results from DVL1 gene mutations. The proteins produced from the genes associated with autosomal dominant Robinow syndrome appear to be part of the same chemical signaling pathways as the ROR2 protein. Mutations in any of these genes alter the production or function of their respective proteins, which impairs chemical signaling that is important for early development.

Some people with the characteristic signs and symptoms of Robinow syndrome do not have an identified mutation in any of the known genes. In these cases, the cause of the condition is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

As discussed above, Robinow syndrome can have either an autosomal recessive or an autosomal dominant 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.

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

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Both the autosomal recessive and autosomal dominant forms of Robinow syndrome are rare.

Fewer than 200 people with autosomal recessive Robinow syndrome have been described in the medical literature. This form of the condition has been identified in families from several countries, including Turkey, Oman, Pakistan, and Brazil.

Autosomal dominant Robinow syndrome has been diagnosed in fewer than 50 families; about 10 of these families have had the osteosclerotic form.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Mesomelia · Very frequent (99-80%)

Shortening of the middle parts of the limbs (forearm and lower leg) in relation to the upper and terminal segments.

Short stature · Very frequent (99-80%)

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Acromesomelia · Frequent (79-30%)

Small hands and feet.

External genital hypoplasia · Frequent (79-30%)

Underdevelopment of part or all of the external reproductive organs.

Hypertelorism · Frequent (79-30%)

Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).

Mesomelic arm shortening · Frequent (79-30%)

Shortening of the middle parts of the arm in relation to the upper and terminal segments.

Small for gestational age · Frequent (79-30%)

Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.

Abnormal heart morphology · Occasional (29-5%)

Any structural anomaly of the heart.

Other findings in the same source

From: Orphanet

Additional reported features include Ankyloglossia (Occasional (29-5%)); Anteverted nares (Occasional (29-5%)); Atrial septal defect (Occasional (29-5%)); Bifid distal phalanx of the thumb (Occasional (29-5%)); Bifid tongue (Occasional (29-5%)); Brachydactyly (Occasional (29-5%)); Broad nasal tip (Occasional (29-5%)); Clitoral hypoplasia (Occasional (29-5%)); Coarctation of aorta (Occasional (29-5%)); Cryptorchidism (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Robinow syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Robinow syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.