Okihiro syndrome is a complex of malformations that primarily affect the upper extremities. Associated with these malformations is a condition called Duane’s anomaly, which prevents patients from looking outward. Treatment is purely symptomatic and usually consists of surgical correction of the individual symptoms.
What is Okihiro syndrome?
Malformation syndromes are congenital disorders that manifest as a complex of malformations of various body components. Okihiro syndrome is one such malformation syndrome. In English-speaking countries, the complex of malformations is called Duane-radial Ray syndrome. The symptoms of the syndrome are mainly related to the upper limbs and are characteristically associated with Duane anomaly of the eyes. The exact prevalence of the syndrome is not known. However, it is estimated to be a rather rare condition with an estimated prevalence of no more than one affected person in every 100,000 people. The malformations manifest immediately after birth and have a hereditary basis. The mode of inheritance is autosomal dominant. Heredity could not be traced in all cases. Thus, despite the general heritability, in many cases a genetic new mutation probably underlies the symptom complex as a cause.
Causes
Okihiro syndrome is caused by genetic mutations in the SALL4 gene on chromosome 20 in gene loci q13.13 to 13.2. Thalidomide-contergan embryopathy results from genetic defects in the same gene. The genetic defects in Okihiro syndrome correspond in most cases to a new mutation of the gene, but may also occur under familial clustering. The SALL4 gene codes for a transcription factor of the same name, which contain instructions for the biosynthesis of proteins. Transcription factors bind specific regions of DNA and keep the function and activity of the corresponding genes under control. Mutations of the SALL4 gene stop one copy of each gene in each body cell from biosynthesizing proteins. Exactly how this connection is causally related to the individual symptoms of Okihiro syndrome is as yet unclear. The influence of external factors on the causative mutation of the gene has also not yet been clarified in detail.
Symptoms, complaints, and signs
Patients with Okihiro syndrome suffer from a complex of clinical symptoms that manifest primarily as malformations of the upper limbs. Often, these malformations are confused with those of Holt-Oram syndrome. In Okihiro syndrome, the multiple malformations are associated with a so-called Duane anomaly. This is a special type of strabismus. Patients are unable to look outward. Limb malformations of the syndrome mainly affect the thumbs. A possible manfestation is, for example, tripartite thumbs, but underdeveloped thumbs are also conceivable. Unlike Holt-Oram syndrome, the thumbs in Okihiro syndrome may also be present in a supernumerary form, corresponding to preaxial polydactyly. Usually, the patients’ thumb malformations are associated with those of the radius. The upper limbs are shortened in many cases. This shortening extends to phocomelia in some cases. In addition to these malformations, renal malformations or unusual positions of this organ are frequently present. Hearing impairment and ear malformations occur in about one-fifth of patients. Malformations of the feet also occur. Heart defects usually involve the atrial septum or correspond to a ventricular septal defect. Less commonly, growth hormone deficiency, short stature, and anal atresia have been observed in patients.
Diagnosis and disease course
The first suspicion of Okihiro syndrome presents itself to the physician by visual diagnosis due to the characteristic malformations of the upper limbs. Suspicion may be further strengthened by imaging of the kidneys and heart. Differentially, syndromes such as thalidomide (thalidomide) embryopathy, Holt-Oram syndrome, and Townes-Brocks syndrome must be excluded. In addition, Okihiro syndrome must be differentiated from thrombocytopenia-absent radius syndrome by differential diagnosis. This differentiation is only possible by a single symptom in some of the syndromes mentioned. The life expectancy of patients with Okihiro syndrome is not further reduced.The severity of the organic malformations determines the prognosis in each individual case.
Complications
Due to Okihiro syndrome, patients suffer from various malformations and deformities. These significantly limit the daily life and quality of life of those affected, so that mental disorders or depression may also occur. Especially in children and adolescents, this can lead to teasing or bullying. The malformations of the Okihiro syndrome mainly affect the limbs and can lead to severe movement restrictions. 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. Also a short stature or a generally delayed development can occur with this syndrome. The children are thus often dependent on the help of other people in their lives. Even in adulthood, this can lead to various complications or complaints. A causal treatment of the Okihiro syndrome is not possible. However, most malformations can be corrected surgically. Usually no complications occur. Furthermore, the life expectancy of the patient is usually not reduced by the syndrome.
When should you see a doctor?
Okihiro syndrome is usually diagnosed immediately after the birth of the child and always requires medical treatment. The various malformations and visual complaints must be examined and treated by the respective specialists. For this, parents should talk to the family doctor or pediatrician, who can recommend suitable doctors. During the treatment of Okihiro syndrome, close consultation with the doctors is also necessary so that any complaints and side effects can be responded to quickly. If the child suffers from severe limb deformities, an orthopedist must also be consulted. Regular physiotherapy is then indicated. Depending on the severity of the condition, further physiotherapeutic measures may be necessary, for example to improve posture or motor skills. Children who suffer from the condition need the help of a doctor throughout their lives. For example, the kidney function must be permanently monitored. In the course of their lives, they may also develop further ear and eye complaints that need to be diagnosed and treated at an early stage. Anyone who is affected themselves or has cases of the disease in the family should have screening carried out at an early stage if they are pregnant. This can help determine if the offspring also has Okihiro syndrome.
Treatment and therapy
A causal therapy is not yet available for people with Okihiro syndrome. For this reason, the syndrome is considered an incurable disease to date. Gene therapy approaches would be the only conceivable option for causal treatment, as they could address the genetic cause. However, these approaches are not yet in the clinical phase. Therefore, Okihiro syndrome must be treated purely symptomatically. Thus, the therapy depends on the symptoms and their severity in the individual case. Therapeutically, the initial focus is on correcting the heart defect. This correction is invasive. Since it is usually a mild heart defect, numerous standard procedures are available for correction. The patient’s renal function must be monitored frequently. If functional kidney dysfunction develops due to the malposition, this syndrome can also be eliminated by surgical intervention by repositioning the kidneys. Form-related impairment of the kidneys can only be corrected by transplantation. In addition to organic malformations, deformities of the extremities are also treated surgically. In addition, strabismus surgery is usually performed to resolve the Duane anomaly. If a hearing test reveals impairments in auditory perception, fitting implants may improve these symptoms. Extremely mild manifestations of Okihiro syndrome may not require invasive surgery.
Outlook and prognosis
Although multifaceted malformations may occur in genetic Okihiro syndrome, the overall prognosis for affected individuals is good. Many of the malformations resulting from spontaneous mutations can be corrected surgically or therapeutically.The life expectancy of those affected by Okihiro syndrome is, on average, the same as for all other people. What is necessary, however, is a comprehensive diagnosis. This must take into account the possible congruence of symptoms in similar diseases. Misdiagnosis may worsen the prognosis. If hearing problems occur due to Okihiro syndrome, they should be detected early. Heart defects or squinting eyes can usually be corrected surgically. The same is true if the mutation has caused malformations of the fingers or extremities. Since individual malformations can be present in varying degrees of severity, the surgical correction options are influenced by this. Sometimes there are permanent movement restrictions, short stature or missing fingers. Such damage cannot be repaired despite modern medical possibilities. These affected persons often need lifelong assistance. 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.
Prevention
External factors influencing the development of Okihiro syndrome are not known so far. For this reason, the syndrome is difficult to prevent. The only preventive measure to date is genetic counseling.
Follow-up
In most cases, those affected by Okihiro syndrome have very few, if any, special aftercare measures available to them. Since it is a genetic disease, the affected person should ideally initiate treatment at a very early stage to prevent worsening of symptoms or other complications. If the patient wishes to have children, genetic testing and counseling may be useful to prevent the recurrence of the syndrome. As a rule, self-healing is not possible. Most of those affected are dependent on regular checks by a doctor. Especially the internal organs should be checked regularly, because especially the heart and the kidneys can be negatively affected by the Okihiro syndrome. Hearing aids can also be used in case of hearing difficulties. Children with Okihiro syndrome have to be supported especially intensively in order to master their everyday life in the best possible way. Loving conversations are often necessary to prevent psychological upsets or depression. Possibly this disease reduces the life expectancy of the affected person, although a general prediction of the further course is usually not possible.
What you can do yourself
In Okihiro syndrome, treatment focuses on surgically treating the individual malformations and providing therapeutic support to the sufferer. The sufferer can contribute to a speedy recovery by maintaining good personal hygiene after the surgical procedures and following the doctor’s instructions regarding physical exercise and dietary measures. In general, a high-protein diet with adequate vitamins and minerals is recommended, as these substances promote wound healing, ensuring rapid recovery. Caffeine, alcohol and spicy foods should be avoided for the first few days to weeks after the procedure. People who have already had several deformities surgically treated usually suffer greatly from the visible scars. Talking to a psychologist helps to cope with the consequences of the condition and to avoid the development of serious psychological complaints. Later in life, it may be useful to seek genetic counseling. Expectant parents in particular should find out about the risks for the child at an early stage and, if necessary, also have a genetic examination so that the necessary preparations can be made before the child is born.
