What is Robinow Syndrome?: Types, Causes, Symptoms, Treatment, Prevention, Diagnosis

Robinow syndrome is recognized as a rare disorder which gets categorized by short-limbed dwarfism, irregularities in the face (facial dysmorphism), head, external genitalia (genital hypoplasia), and vertebral segmentation.¹ Robinow syndrome was initially described by human geneticist Meinhard Robinow in the year 1969. Other physicians who were involved were Hugo D. Smith and Frederic N. Silverman. Let us understand about the types, causes, symptoms, diagnosis and treatment of Robinow syndrome in detail.

There are two types of Robinow syndrome which get differentiated by signs and symptoms, mode of inheritance, severity, and the genes that are linked with them.
The two main types of Robinow syndrome are-

Autosomal Recessive Robinow Syndrome- Autosomal recessive Robinow syndrome results in the shortening of the long bones present in the legs and arms, wedge-shaped spinal bones resulting in kyphoscoliosis, short toes and fingers, short stature, missing or fused ribs, and unique facial characteristics. However, there are other features too that include underdeveloped genitalia, heart or kidney defects, dental problems, or late development. Robinow syndrome is caused due to mutations in the ROR2 gene.

Autosomal Dominant Robinow Syndrome- Robinow syndrome causes milder but somewhat similar features. There is hardly any rib and spine abnormality and short stature too is less severe. An irregular kind of this form is furthermore categorized by osteosclerosis. Robinow syndrome is the result of a mutation in the DVL or WNT5A gene.

At times, the actual causes of Robinow syndrome remains unknown, and management might comprise surgery or bracing for skeletal abnormalities.

The autosomal recessive as well as autosomal dominant types of Robinow syndrome are the result of changes in various genes. The autosomal form happens because of mutations in the gene ‘ROR2’ resulting in a shortage of ‘ROR2’ protein.2 When this protein is not present, then development gets disrupted especially in the creation of the heart, genitals, and the skeleton. The reason for autosomal dominant Robinow syndrome is mutations in the gene ‘WNT5A or DVL1’ gene, thus, resulting in a shortage of particular proteins that are important for the general development. Nonetheless, a few people suffering from Robinow syndrome suffer from a shortage of having no mutation of these genes, and in this condition, the cause remains unknown.

The majority of the genetic diseases get determined by the position of the two copies of one gene. Here, one is received from the mother and another one from the father. Recessive genetic disorders happen when a person inherits a couple of copies of an unusual gene for the identical mannerisms, one from each parent. When a person inherits a normal gene and a gene for the disorder, then the individual becomes a carrier for the disorder but generally won’t show any symptom.

All the people carry four or five abnormal genes but do not show up Robinow syndrome due to the presence of other normal gene. However, parents who happen to be close relatives may be carriers of defective genes, which can be passed on to their children, resulting in dominant condition. Thus the risk of suffering from Robinow syndrome is high in such cases, as compared to unrelated parents.

The signs and symptoms of Robinow syndrome are determined by the particular variant a person possesses. The recognizable signs and symptoms become apparent at the time of infancy or early childhood.

The symptoms of Robinow syndrome in the autosomal recessive form include the following-

• The facial features are jointly known as ‘fetal facies’ as they look close to those of a fetus during development.
• Broad forehead
• Widely spaced eyes
• Upturned tip of the nose
• Broad nasal bridge
• Mouth gets shaped like a triangle.
• Short stature; short fingers and toes and short bones in the patients’ legs and arms
• Overgrowth of the gums and crowded teeth
• Hemivertebrae (wedge-shaped bones in the patient’s spine), kyphoscoliosis (abnormally-shaped spine)
• Difficulty in feeding or eating
• Recurrent ear infections and difficulty in hearing
• Respiratory problems, like breathing difficulties
• Hypotonia (low muscle tone)
• Genital abnormalities, like a small penis and testes in males that give rise to hypogonadism.
• Kidney malfunction and kidney defects resulting in lessened urine output
• Congenital heart defects that give rise to signs and symptoms of unusual functioning of the heart
• Incapability to reach developmental milestones that happen in nearly 10-15% of the babies.

The symptoms of Robinow syndrome in the autosomal dominant form include the following-

• Typical facial features that are witnessed in the autosomal recessive type, but it tend to be milder.
• Hypogonadism due to genital abnormalities, like a small penis and testes in males.
• Extra teeth in the patient’s mouth compared to what is normally seen and overgrowth of gums.
• An umbilical hernia, where the intestine bulges via the abdominal wall, commonly through the belly button.
• Low muscle tone, also known as hypotonia.
• Respiratory problems
• Regular ear infections and problems in hearing
• Esophageal reflux
• Congenital heart defects that result in signs and symptoms of unusually functioning heart.

The diagnosis of Robinow syndrome might be performed prior to or post birth. The diagnosis procedure is dependent on the following processes-

• Physical examination of both mother and the child
• Assessment of family medical history
• Assessment of symptoms
• X-ray for detecting or confirming bone abnormalities
• Ultrasound of the fetus for checking any morphological abnormalities
• Hormonal blood tests for detecting the male hormonal levels.
• Genetic examination of fetal cells for checking for any mutation feature of Robinow syndrome.

Some children do not suffer from specific gene mutations despite having distinctive signs and symptoms. So, for these children, a diagnosis is made by analyzing the grouping of signs and symptoms. However, numerous clinical conditions do have similar symptoms. Hence, your healthcare provider might perform extra tests for ruling out various other clinical conditions for arriving at a conclusive diagnosis of Robinow syndrome.

The following are the probable complications of Robinow syndrome-

• Obstruction of the flow of blood to the pulmonary stenosis resulting in labored breathing, fatigue, and chest pain. However, it can lead to heart failure too.
• The risk of pneumonia in infants
• Growing and developmental delays in a child
• Kidney abnormalities which can result in chronic renal failure
• Narrowing of openings in the body. Children who are suffering from Robinow syndrome can suffer from small nasal opening or small anus.

Actually, there isn’t any particular guideline or method to prevent this disorder as it happens to be a genetic ailment. However, some preventive measures are-

• Genetic examination and screenings of the expecting parents and also of the related family members. Also, a prenatal diagnosis can help in getting an understanding of the dangers better at the time of pregnancy.
• When there is a family history of Robinow syndrome, genetic counseling does help in assessing risks before pregnancy.
• Currently, active research is being performed for exploring both prevention as well as treatment processes for genetic diseases, like Robinow syndrome.
• Again, regular medical screening happening at periodic intervals along with physical examinations and tests are highly advised.

Actually, there isn’t any cure for this disorder and the treatment process is geared towards managing the indications of this condition. The treatment of Robinow syndrome mainly aims at managing the symptoms.

• Surgery
• Bracing
• Physiotherapy

• Surgery for correcting undescended testis
• Surgery for correcting other related abnormalities, like a small penis.

• Braces
• Surgery
• Treatment For Congenital Heart Defects- Appropriate treatment options, like surgery, might be advised.

• The treatment of growth hormone for overcoming short stature
• Special social support
• Special education
• Vocational training support.
• For Gastrointestinal Abnormalities- In case of gastrointestinal reflux disease and inguinal hernia, special medicines are recommended.

A child who is suffering from Robinow syndrome does require a team of experts from different fields who are working in cooperation for permitting the child towards a normal development. Rehabilitation therapies may be useful to a great extent and must be done, as advised by the medical team.

In the case of Robinow syndrome, early diagnosis and intervention is highly important. It is vital to ensure that children suffering from Robinow syndrome reach their potential. At times, special services turn highly beneficial to the affected children and special services include support system, special remedial education, physical therapy, and various social, vocational, and medical services. In fact, genetic counseling too is suggested for the affected people and their families. Other treatment procedure for Robinow syndrome includes supportive and symptomatic.

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126946/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1735132/pdf/v039p00305.pdf