Yunis Varon Syndrome: Causes, Symptoms & Treatment

Yunis-Varon syndrome is a multisystem disorder that is one of the skeletal dysplasias. The complex of symptoms is caused by a mutation of the FIG4 gene and is inherited in an autosomal recessive manner. To date, there is no causal therapy.

What is Yunis-Varon syndrome?

The disease group of skeletal dysplasias includes diseases with congenital disorders of bone and cartilage tissue. Skeletal dysplasias are tissue defects instead of organ defects. Yunis-Varon syndrome corresponds to a rare skeletal dysplasia from a symptom complex with the main features of kleidocranial dysostosis. This term is used to describe changes in the face and clavicles. In addition to the kleidocranial dystosis, micrognathia is present in Yunis-Varon syndrome. Furthermore, the patient’s thumb is often not applied. The symptom complex is therefore often referred to as kleidocranial dysplasia with micrognathism and absent thumb. The symptom complex was first described at the end of the 20th century by the Colombian human geneticists E. Yunis and H. Varón, whose names coined the symptom designation. Yunis-Varon syndrome is one of the unspecified congenital malformation syndromes and has a hereditary component. The symptom complex is also often classified as a multisystem disorder because it can affect multiple organ systems.

Causes

Yunis-Varon syndrome shows an extremely low frequency, with a prevalence of one case in 1,000,000. The symptom complex does not occur sporadically. Instead, familial clustering has been observed. Inheritance appears to be in the autosomal recessive mode. The cause of the skeletal malformations is a genetic mutation. The causative gene has now been identified. Thus, a mutation in the FIG4 gene at gene locus 6q21 seems to cause the symptoms. This gene codes for the FIG4 phosphoinositide 5-phosphatase. Due to the mutation of the encoding gene, the catalyzing enzyme is defective and performs its tasks inadequately. This connection causes the Yunis-Varon syndrome with its individual symptoms. Science has now reached a consensus on the genetic components and the basis of the genetic disposition. Which further factors play a role for the manifestation at the individual with a genetic disposition to this effect is up to now a subject of speculation.

Symptoms, complaints, and signs

Like any other syndrome, Yunis-Varon syndrome is characterized by a combination of certain clinical symptoms and criteria. The manifestation of symptoms exists at birth. Among the most striking manifestations are the facial abnormalities. These anomalies include, above all, the typical micrognathia, which corresponds to an underdevelopment of the upper and lower jaw. The cranial sutures of the patients are also wide open cranial sutures. This mainly affects the frontal sutures. The palate is narrow and falls out high. The patients’ auricles also often sit low. In many cases, those affected with dolichocephaly show more or less severe long-headedness. In infancy, disorders and delays in tooth development also occur as accompanying symptoms. The clavicles of the patients are either underdeveloped or not developed at all. In addition to aplasia of the clavicles, aplasia of the thumb is present in almost all cases. This non-development of the thumb may be associated with a lack of development of other phalanges, especially in the second to fifth rays. In addition, the big toe of the affected person is often underdeveloped. Complete aplasia is less common in the foot. In some cases, the syndrome affects not only the bony system but additionally the cardiopulmonary system and the skin.

Diagnosis and course of the disease

The first suspicion of Yunis-Varon syndrome occurs to the physician immediately after birth via mere visual diagnosis. Differential diagnosis must be made for diseases such as isolated kleidocranial dysplasia in the sense of mandibular hypoplasia or isolated mandibuloacral dysplasia in the sense of thumb aplasia. One of the tools available for confirming the diagnosis is imaging such as radiographic imaging. The X-ray shows the aplasia of the clavicles and, if necessary, the wide-open cranial sutures.Molecular genetic testing may be ordered to confirm the diagnosis. If genetic analysis reveals evidence of mutation on gene FIG4 gene in gene locus 6q21, the diagnosis of Yunis-Varon syndrome is considered confirmed.

Complications

The symptoms of Yunis-Varon syndrome are very diverse and in most cases severely restrict the daily life of the affected person. In this case, patients suffer from malformations and deformities since birth. There is also a cleft palate, and many affected people also have a long head. The development of the teeth is also significantly disturbed and restricted by the Yunis-Varon syndrome, so that the affected persons are dependent on regular visits to the dentist during their lives. Furthermore, the affected person also lacks the collarbones or the thumbs, so that movement restrictions can occur. The children are dependent on the help of other people and cannot easily cope with everyday life on their own. There are also symptoms of the heart or lungs, which in the worst case can lead to the death of the affected person. As usually only symptomatic treatment of Yunis-Varon syndrome is possible, no particular complications occur. The symptoms are cured by various surgical interventions and medications, although a positive course of the disease cannot be predicted in every case. Possibly, Yunis-Varon syndrome also reduces the patient’s life expectancy.

When should you see a doctor?

People whose family has a relative diagnosed with Yunis-Varon syndrome should always contact a doctor if they are planning to have offspring themselves. An explanation of the possible risks is advisable so that all options can be weighed up against each other. Since the disease causes visual abnormalities, these can be noticed by visual contact immediately after delivery. Under normal circumstances, a birth will take place in an inpatient setting, a birth center, or in the home environment. In almost all cases, obstetricians or attending physicians are present. These take over the initial examinations of the child quite automatically in a predetermined and routine work process. Parents and relatives are therefore under no compulsion to act. Visual abnormalities in the facial area lead to further examinations being initiated. A diagnosis is ultimately reached via medical tests. If the birth takes place without the presence of midwives or medical personnel, an ambulance should be alerted immediately after delivery or the baby should be taken to the hospital. If there are malformations, visual irregularities of the entire skeletal system or many limbs, the newborn child needs. Movement disorders, skin abnormalities or open wounds need medical and medical attention as soon as possible.

Treatment and therapy

Causal treatment of Yunis-Varon syndrome would require gene therapy. Because gene therapy procedures are currently the subject of medical research but have not yet been considered for use, no causal therapy for the symptom complex is available at this time. Treatment is symptomatic and is accordingly based on the symptoms in the individual case. Corrective dental surgery is a possible treatment measure, as are orthopedic surgical corrections. How urgent certain corrections are or whether they make sense at all depends primarily on the doctor’s assessment of the severity and risk of subsequent complaints. For example, some of the malformations may promote secondary problems such as airway obstruction and should be resolved as soon as possible in such a case. Weighing the risks and benefits is central to surgical interventions and corrective procedures. Since respiratory insufficiency also represents a possible risk for the affected person, close monitoring of the patient usually takes place. Reconstruction of the thumb may be useful because the thumb in particular is irreplaceable for a variety of everyday movements, and the lives of affected individuals are affected to a greater or lesser degree by the nonunion of the finger.

Prevention

To date, Yunis-Varon syndrome cannot be prevented because it is a genetic disorder favored by mutational factors that have not been identified.

Aftercare

The affected person usually has only very limited measures of direct aftercare available to him or her in Yunis-Varon syndrome, since it is a congenital disease that usually cannot be completely cured either. Therefore, the affected person should ideally consult a doctor at the first signs and symptoms of the disease and also initiate treatment to prevent the occurrence of other symptoms. Genetic testing and counseling is also very useful if the person wishes to have children, in order to prevent the syndrome from occurring in their descendants. Most of the affected persons are dependent on various surgical interventions for this disease, with which the complaints and the malformations can usually be well alleviated. In any case, the affected person should rest and take it easy after the operation. Physical exertion or stress should be avoided in order not to put unnecessary strain on the body. Often, the support of one’s own family is also very important with this disease. Loving conversations are also important so that it does not come to depression or other psychological complaints in the affected person.

This is what you can do yourself

Patients with Yunis-Varon syndrome should know their own physical limits well and always take them into account in everyday activities. Otherwise, symptoms may increase or further irreversible damage to the skeletal system may set in. The disease poses a challenge not only to the patient, but also to relatives or people in the close social environment. In everyday life, it is therefore necessary to deal with the disease in the best possible way for everyone involved. The mental strength and self-confidence are to be supported by daily success experiences or necessary encouragement. The use of psychotherapeutic support has proven to be helpful. On this way methods can be learned, which can lead to an alleviation of the mental stress. The consumption of harmful substances such as alcohol or nicotine should be avoided. The organism needs an adequate supply of oxygen and the immune system depends on a healthy as well as balanced diet. Disturbances of the respiratory supply should be avoided, as they can quickly lead to a life-threatening development. Close and trusting cooperation with the treating physicians is particularly important. Only in this way can the treatment results be optimized and measures of long-term improvement be taken in advance. The disease is not curable and is dependent on lifelong therapies.