Yunis Varon Syndrome

By | June 10, 2022

Yunis-Varon syndrome is a multisystem disease that is classified as a skeletal dysplasia. The complex of symptoms is triggered by a mutation in the FIG4 gene and is inherited in an autosomal recessive manner. So far, there is no causal therapy.

What is Yunis Varon Syndrome?

Diseases with congenital disorders of the bone and cartilage tissue are included in the disease group of skeletal dysplasia. Skeletal dysplasias are tissue defects rather than organ defects. The Yunis-Varon syndrome corresponds to a rare skeletal dysplasia from a symptom complex with the main features of the cerebrospinal dysostosis. For meaning of cradle cap in English, please visit

This term describes changes in the face and collarbones. Micrognathia is also present in Yunis-Varon syndrome in addition to clodocranial dystosis. In addition, the thumb of the patient is often not attached. The symptom complex is therefore often referred to as clodocranial dysplasia with micrognathism and a missing 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 disease because it can affect multiple organ systems.


Yunis-Varon syndrome has an extremely low incidence, with a prevalence of one case in 1,000,000. The symptom complex does not occur sporadically. Instead, familial clusters were observed. Inheritance appears to be autosomal recessive. The cause of the skeletal malformations is a genetic mutation. The causative gene has now been identified.

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 coding gene, the catalysing enzyme is defective and only inadequately fulfills its tasks. This connection causes the Yunis-Varon syndrome with its individual symptoms.

Science has now come to an agreement on the genetic components and the basis of the genetic disposition. What other factors play a role in the manifestation in the individual with a genetic disposition to that effect has so far been the subject of speculation.

Symptoms, Ailments & Signs

Like any other syndrome, Yunis-Varon syndrome is characterized by the combination of certain clinical symptoms and criteria. The manifestation of symptoms already exists at birth. One of 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 seams. The palate is narrow and falls high. The auricles of the patients are also often deep. In many cases, those affected with dolichocephaly show a more or less severe long-headedness. Disturbances and delays in tooth development also occur in infancy.

The patients’ collarbones are either underdeveloped or not formed at all. In addition to the aplasia of the clavicles, aplasia of the thumb is present in almost all cases. This non-contact of the thumb can be associated with a lack of contact with other finger phalanxes, especially in the second to fifth ray.

The big toe of those affected is also often underdeveloped. Total aplasia is less common in the foot area. In some cases, the syndrome affects not only the bony system, but also the cardiopulmonary system and the skin.

Diagnosis & course of disease

The first suspicion of Yunis-Varon Syndrome overtakes the doctor immediately after birth through a visual diagnosis. Diseases such as isolated clodocranial dysplasia in the sense of hypoplasia of the lower jaw or isolated mandibuloacral dysplasia in the sense of thumb aplasia must be differentiated in terms of differential diagnosis. On the one hand, imaging such as X-ray imaging is available as an instrument for confirming the diagnosis.

The X-ray shows the aplasia of the clavicles and possibly the wide open cranial sutures. Molecular genetic tests can be ordered to confirm the diagnosis. If the genetic analysis provides evidence of a mutation on the gene FIG4 gene in the gene locus 6q21, the diagnosis of Yunis-Varon syndrome is considered secure.


The symptoms of Yunis-Varon syndrome are very diverse and in most cases severely restrict the everyday life of those affected. The patients have suffered from malformations and malformations since birth. A cleft palate also occurs, with many sufferers also experiencing long-headedness.

The development of the teeth is also significantly disturbed and restricted by the Yunis-Varon syndrome, so that those affected are dependent on regular visits to the dentist in their lives. Furthermore, the affected person is also missing the collarbones or the thumbs, which can lead to restricted mobility. The children are dependent on the help of other people and cannot easily cope with everyday life on their own.

There are also heart or lung problems, which in the worst case can lead to the death of the person concerned. Since, as a rule, only symptomatic treatment of Yunis-Varon syndrome is possible, no particular complications arise. The complaints are cured by various surgical interventions and medication, although a positive course of the disease cannot be predicted in every case. Yunis-Varon syndrome may also reduce the patient’s life expectancy.

When should you go to the doctor?

People in whose family a member has been diagnosed with Yunis-Varon syndrome should always consult a doctor if they are planning children themselves. It is advisable to be informed about possible risks so that all options can be weighed up against each other. Since the disease causes visual abnormalities, these can be seen immediately after the birth by visual contact. Under normal circumstances, birth takes place in an inpatient setting, a birthing center or in a home environment.

In almost all cases, obstetricians or attending physicians are present. In a predetermined and routine work process, they automatically take over the child’s initial examinations. Parents and relatives are therefore not obliged to act. Optical abnormalities in the area of ​​the face lead to further examinations being initiated. A diagnosis is ultimately made using medical tests.

If the birth takes place without the presence of midwives or medical staff, an ambulance must be alerted immediately after the birth or the way to the hospital must be sought. If there are malformations, optical irregularities can be seen in the entire skeletal system or many limbs, the newborn child needs. Movement disorders, skin abnormalities or open wounds must be treated medically and medically as quickly as possible.

Treatment & Therapy

Gene therapy would have to take place for the causal treatment of Yunis-Varon syndrome. Since gene therapy methods are currently a subject of medical research, but are not yet suitable for use, there is currently no causal therapy available for the symptom complex. The treatment is symptomatic and is based on the symptoms in the individual case.

Corrective dental surgery can also be considered as a treatment measure, as can 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 the risk of subsequent problems.

Under certain circumstances, some of the malformations can promote subsequent problems such as airway obstructions and should be resolved as quickly as possible in such a case. The weighing of risks and benefits is the focus of operational measures and corrections. Since respiratory insufficiency also represents a possible risk for those affected, the patients are usually closely monitored.

A reconstruction of the thumb can make sense, since the thumb is indispensable for a large number of everyday movements and the life of those affected is more or less severely impaired by the non-placement of the finger.


So far, Yunis-Varon syndrome cannot be prevented because it is a genetic disease that is favored by unidentified mutation factors.


Those affected with Yunis-Varon syndrome usually only have very limited direct aftercare measures available, since this is a congenital disease that usually cannot be completely cured. Therefore, ideally, the person affected should 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 you want to have children, in order to prevent the syndrome from occurring in the offspring. Most of those affected are dependent on various surgical interventions with which the symptoms and deformities can usually be alleviated well.

The person concerned should definitely rest and rest after the procedure. Physical exertion or stress should be avoided in order not to unnecessarily burden the body. The support of one’s own family is often very important with this illness. Loving conversations are also important so that the person concerned does not develop depression or other psychological problems.

You can do that yourself

Patients with Yunis-Varon syndrome should know their own physical limits well and always take them into account in everyday life. Otherwise, the symptoms can increase or further irreversible damage to the skeletal system can occur.

The disease not only poses a challenge for the patient, but also for the relatives or people in the immediate social environment. In everyday life, dealing with the disease must therefore be organized as best as possible for everyone involved. Mental strength and self-confidence are to be supported by daily achievements or necessary encouragement. The use of psychotherapeutic support has proven to be helpful. In this way, methods can be learned that can lead to an alleviation of mental stress.

The consumption of harmful substances such as alcohol or nicotine should be avoided. The organism needs a sufficient supply of oxygen and the immune system depends on a healthy and balanced diet. Disturbances in the respiratory system should be avoided as they can quickly lead to a life-threatening development.

The close and trusting cooperation with the treating physicians is particularly important. Only in this way can the treatment results be optimized and measures for long-term improvement can be taken in advance. The disease is incurable and dependent on lifelong therapies.

Yunis Varon Syndrome