Okihiro Syndrome

Okihiro syndrome is a complex of malformations that primarily affect the upper extremities. These malformations are associated with a so-called Duane anomaly, which prevents the patient from seeing the outside world. The treatment is purely symptomatic and usually consists of surgical corrections of the individual symptoms.

Okihiro Syndrome

What is Okihiro Syndrome?

Malformation syndromes are congenital diseases that manifest themselves as a complex of malformations in various parts of the body. Okihiro syndrome is one such malformation syndrome. In English-speaking countries, the complex of malformations is referred to as Duane radial ray syndrome. See acronymmonster for Definition of Heat Exhaustion in English.

The symptoms of the syndrome relate primarily to the upper limbs and are characteristically associated with a Duane anomaly of the eyes. The exact prevalence of the syndrome is not known. However, it is estimated that it is a rather rare disease with an estimated prevalence of at most one affected person in 100,000.

The malformations manifest themselves immediately after birth and have a hereditary basis. The inheritance corresponds to the autosomal dominant inheritance. Inheritance could not be traced in all cases. Despite the general hereditary nature, the symptom complex in many cases is probably based on a new genetic mutation as the cause.


Okihiro syndrome is caused by genetic mutations in the SALL4 gene on chromosome 20 at gene loci q13.13 to 13.2. Thalidomide Contergan embryopathy is due to genetic defects in the same gene. In most cases, the genetic defects in Okihiro syndrome correspond to a new mutation of the gene, but they can also run in families.

The SALL4 gene encodes a transcription factor of the same name that contains instructions for the biosynthesis of proteins. Transcription factors bind to specific regions of DNA and control the function and activity of the relevant genes. Mutations in the SALL4 gene prevent one copy of the gene in each cell from the biosynthesis of proteins.

How exactly this connection is causally related to the individual symptoms of Okihiro syndrome is not yet clear. The influence of external factors on the causative mutation of the gene has not yet been clarified in detail.

Symptoms, Ailments & Signs

Patients with Okihiro syndrome suffer from a complex of clinical symptoms, which primarily manifest as deformities of the upper limbs. These malformations are often confused with those of Holt-Oram syndrome. The multiple malformations in Okihiro syndrome are associated with a so-called Duane anomaly.

This is a special kind of strabismus. Patients cannot see outside. Limb malformations of the syndrome primarily affect the thumbs. A possible manifestation is, for example, the tripartite structure of the thumb, but underdeveloped thumbs are also conceivable.

Unlike in Holt-Oram syndrome, the thumbs in Okihiro syndrome can also be supernumerary and thus correspond to preaxial polydactyly. As a rule, the thumb malformations of the patients are associated with those of the radius. The upper limbs are shortened in many cases. In some cases, this shortening can even lead to phocomelia.

In addition to these malformations, there are often kidney malformations or unusual positions of this organ. Hearing impairments and ear malformations occur in about one fifth of patients. There are also foot deformities. Heart defects usually affect the atrial septum or correspond to a ventricular septal defect. Less frequently, growth hormone deficiency, short stature and anal atresia were observed in the patients.

Diagnosis & course of disease

The first suspicion of Okihiro syndrome is presented to the doctor by visual diagnosis due to the characteristic malformations of the upper limbs. The suspicion can be further strengthened by imaging of the kidneys and the heart. Syndromes such as thalidomide (contergan) embryopathy, Holt-Oram syndrome and Townes-Brocks syndrome must be excluded in the differential diagnosis.

In addition, the Okihiro syndrome must be differentiated from the thrombocytopenia absent radius syndrome. In some of the syndromes mentioned, this distinction can only be made by a single symptom. The life expectancy of patients with Okihiro syndrome is not further reduced. The severity of the organic malformations determines the prognosis in the individual case.


Due to Okihiro Syndrome, patients suffer from various malformations and deformities. These restrict the everyday life and quality of life of those affected considerably, so that mental disorders or depression can also occur. This can lead to teasing or bullying, especially in children and young people. The malformations of Okihiro syndrome primarily affect the limbs and can lead to severe limitations in movement.

The fingers are also affected, so that the children are restricted in their development. Furthermore, the patients suffer from malformations of the ears due to the syndrome and thus also from various hearing problems. Short stature or a general delayed development can also occur with this syndrome.

The children are often dependent on the help of other people in their lives. Various complications or complaints can also occur in adulthood. A causal treatment of Okihiro syndrome is not possible. However, most malformations can be corrected surgically. Usually there are no complications. Furthermore, the life expectancy of the patient is usually not reduced by the syndrome.

When should you go to the doctor?

Okihiro syndrome is usually diagnosed immediately after the birth of the child and always requires medical treatment. The various malformations and visual problems must be examined and treated by the respective specialists. Parents should speak to their family doctor or pediatrician, who can recommend suitable doctors. During the treatment of Okihiro syndrome, close consultation with the doctor is also necessary so that any symptoms and side effects can be reacted to quickly. If the child suffers from severe limb deformities, an orthopedist must also be consulted. Regular physiotherapy is then indicated.

Je nach Schwere der Erkrankung sind weitere physiotherapeutische Maßnahmen notwendig, um beispielsweise die Körperhaltung oder die motorischen Fähigkeiten zu verbessern. Kinder, die an den Beschwerden leiden, benötigen ihr gesamtes Leben über die Hilfe eines Arztes. So muss etwa die Nierenfunktion dauerhaft überwacht werden.

Auch kann es im Verlauf des Lebens zu weiteren Beschwerden der Ohren und der Augen kommen, die frühzeitig diagnostiziert und therapiert werden müssen. Wer selbst betroffen ist oder Fälle der Erkrankung in der Familie hat, sollte bei einer Schwangerschaft frühzeitig ein Screening durchführen lassen. So kann festgestellt werden, ob der Nachwuchs ebenfalls an dem Okihiro-Syndrom leidet.

Behandlung & Therapie

A causal therapy is not yet available for people with Okihiro syndrome. For this reason, the syndrome has so far been considered an incurable disease. Gene therapy approaches would be the only conceivable option for causal treatment, since they could eliminate the genetic cause. However, these approaches are not yet in the clinical phase. Therefore, Okihiro syndrome must be treated purely symptomatically.

The therapy depends on the symptoms and their severity in the individual case. Therapeutically, the focus is primarily on correcting the heart defect. This correction is invasive. Since it is usually a mild heart defect, numerous standard procedures are available for correction. Patients’ renal function must be monitored frequently.

If a functional disorder of the kidneys occurs as a result of the malposition, this syndrome can also be eliminated by means of a surgical intervention by repositioning the kidneys. Shape-related impairments of the kidneys can only be corrected by a transplant. In addition to organic malformations, deformities of the extremities are also treated surgically.

In addition, a squint operation is usually performed to resolve the Duane anomaly. If a hearing test reveals impairments in auditory perception, a treatment with implants can improve these symptoms under certain circumstances. Extremely mild forms of Okihiro syndrome may not require invasive surgery.

Outlook & Forecast

Even if a variety of malformations can occur in genetic Okihiro syndrome, the prognosis for those affected is good overall. Many of the malformations caused by spontaneous mutations can be corrected surgically or therapeutically. The average life expectancy of those affected by Okihiro syndrome is just as high as that of all other people.

What is necessary, however, is a comprehensive diagnosis. This must take into account the possible congruence of the symptoms in similar diseases. A misdiagnosis can worsen the prognosis. If hearing problems occur as a result of Okihiro syndrome, these should be recognized at an early stage. Heart defects or squinting eyes can usually be corrected surgically. The same is also the case if the mutation has caused deformities in the fingers or extremities.

Since individual malformations can be present in different degrees of severity, the surgical correction options are influenced by this. Sometimes there are permanent restrictions on movement, short stature or missing fingers. Such damage cannot be repaired despite modern medical possibilities. Those affected often need lifelong support.

It is also problematic that bullying can occur at school because of the different appearance of the affected children. In such cases, mental illness, feelings of inferiority or depression occasionally occur. The better the results of symptomatic treatment and surgical measures, the more positive the prognosis for those affected.


External factors influencing the development of Okihiro syndrome are not yet known. For this reason, the syndrome is difficult to prevent. So far, the only preventive measure is genetic counseling.


In most cases, those affected with Okihiro syndrome have very few or no special follow-up measures available. Since this is a genetic disease, the person affected should ideally start treatment very early on so that the symptoms do not worsen or other complications occur.

If you want to have children, genetic testing and counseling can be useful to prevent the syndrome from reoccurring. Normally, self-healing cannot occur. Most of those affected are dependent on regular check-ups by a doctor. The internal organs in particular should be checked regularly, since the heart and kidneys in particular can be negatively affected by Okihiro syndrome.

Hearing aids can also be used if you have hearing problems. Children with Okihiro Syndrome need to be supported particularly intensively in their lives in order to master their everyday life in the best possible way. Loving conversations are often necessary to prevent mental upsets or depression. This disease may reduce the life expectancy of those affected, although a general prediction of the further course is usually not possible.

You can do that yourself

In the case of Okihiro syndrome, treatment focuses on surgically treating the individual malformations and providing therapeutic support for those affected. The patient can help speed recovery by maintaining good personal hygiene after surgery and following the doctor’s instructions for exercise and diet.

In general, a high-protein diet with sufficient vitamins and minerals is recommended, as these substances promote wound healing and thus ensure rapid healing. Caffeine, alcohol and spicy foods should be avoided in the first few days to weeks after the procedure. People who have already had several malformations surgically treated usually suffer greatly from the visible scars. A conversation with a psychologist helps to process the consequences of the illness and to avoid the development of serious mental problems.

In later life, it may make sense to seek genetic counseling. In particular, expectant parents should find out about the risks for the child at an early stage and, if necessary, have a genetic test carried out so that the necessary preparations can be made before the child is born.