Yunis-Varon Syndrome (YVS), also known as cleidocranial dysplasia, is a rare genetic disorder characterized by skeletal and ectodermal abnormalities. It follows an autosomal recessive pattern of inheritance and is caused by mutations in the FIG4 gene.
The disorder presents with structural brain abnormalities, facial dysmorphisms, sparse and pale hair, and enlarged vacuoles in neurons, muscles, and cartilage. Symptoms and signs of YVS are usually present from birth, with affected infants often being small, having slowed growth, and experiencing difficulties with feeding.
The history of YVS dates back to 1980 when Yunis and Varon first described the disorder in five children from three families. The characteristic symptoms observed included absent clavicles, macrocrania, diastasis of sutures, absent thumbs and distal phalanges of fingers, and micrognathia. The term “Yunis-Varon syndrome” was coined in 1983 by Hughes and Partington.
YVS is caused by mutations in the FIG4 gene, which encodes the FIG4 protein. This protein plays an important role in endosome and lysosome activity. FIG4 deficiency results in a decrease in phosphatidylinositol 3,5-biphosphate (PI(3,5)P2), leading to endosome/endolysosome/lysosome dysfunction. FIG4 is also associated with other conditions, including Charcot-Marie-Tooth Disease 4J and Amyotrophic Lateral Sclerosis 11.
The symptoms and manifestations of YVS are diverse, involving various systems in the body. These include orthopedic, cardiovascular, and endocrine abnormalities. Specific features commonly observed include aplasia of the distal phalanx of the hallux and hand, agenesis of the corpus callosum, anteverted nares, cardiomegaly, dolichocephaly, and high forehead. Dental anomalies such as supernumerary teeth and insufficient cementum can also be present.
YVS is a rare disease, with less than 30 cases reported worldwide. Its incidence and prevalence in different ethnicities are still being studied. Diagnosis of YVS can be made based on clinical evaluation and confirmation through FIG4 mutation testing. Antenatal screening using ultrasonography can also detect the syndrome in infants with skeletal or cardiac abnormalities.
Treatment for YVS involves managing the signs and symptoms exhibited by each individual since there is no cure for the condition. Orthopedic specialists can address bone and skeletal abnormalities, while syndactyly can be treated with surgery. Other interventions, such as the use of a ventilator, may be required for severe breathing problems.
Early intervention and special services are essential for individuals with YVS, and genetic counseling can provide support to affected individuals and their families. Although the prognosis for YVS is generally poor, survival into adulthood is possible.
– National Organization for Rare Disorders
– Journal of Human Genetics