About yunis varon syndrome
What is yunis varon syndrome?
Yunis-Varon syndrome is an extremely rare genetic multisystem disorder with defects affecting the skeletal system, ectodermal tissue (hair and teeth); and cardiorespiratory (i.e., heart and lungs) systems. It is characterized by large fontanelles, clavicular hypoplasia, characteristic facial features and/or abnormalities of fingers and toes. Characteristic features may include microcephaly, ear abnormalities, anteverted nares, midfacial hypoplasia, tented upper lip and small jaw (micrognathia), sparse or absent eyebrows and/or eyelashes. Abnormalities of the fingers and toes may include absence (aplasia) or underdevelopment (hypoplasia) of the fingers and toes. In most cases, infants with this disorder experience severe feeding problems and respiratory difficulties. In addition, affected infants may have heart defects (e.g., abnormal enlargement of the heart muscle [hypertrophic cardiomyopathy]). Frequently, feeding problems, respiratory difficulties, and/or heart defects may result in life-threatening complications during infancy. Yunis-Varon syndrome is inherited as an autosomal recessive trait.
What are the symptoms for yunis varon syndrome?
Yunis-Varon syndrome is a rare genetic multisystem disorder characterized by large fontanelles, clavicular hypoplasia, characteristic facial features and/or abnormalities of fingers and toes. Characteristic features may include microcephaly, ear abnormalities, anteverted nares, midfacial hypoplasia, tented upper lip and small jaw (micrognathia), sparse or absent eyebrows and/or eyelashes.
As infants with Yunis-Varon syndrome mature, they may also exhibit failure to gain weight or grow at the expected rate (failure to thrive), severe developmental delays, and/or intellectual disability.
Infants with Yunis-Varon syndrome exhibit absence or severe underdevelopment (hypoplasia) of one or both of the collarbones (clavicles) and delayed closure of the two soft membraned-covered openings (fontanels) on an infant’s head, with abnormal separation of the fibrous joints (sutures) that connect certain bones of the skull. Children without collarbones or with underdeveloped collarbones may have “droopy” shoulders or, in extreme cases, may be able to bring their shoulders together in front of their bodies.
Infants with Yunis-Varon syndrome also have abnormalities of the fingers and toes (digits). The thumbs and the bones at the ends of the fingers and the great toes (distal phalanges) may be absent (aplastic) or underdeveloped (hypoplastic). In some cases, other bones may be underdeveloped including the bones between the wrists and the fingers (metacarpals), the bones between the knuckles of the fingers (middle phalanges), the bones of the great toes nearest to the feet (proximal phalanges) or other toes, and/or the bones between the ankles and the toes (metatarsals). As a result of these abnormalities, the fingers and toes may be unusually short. In addition, some affected infants may exhibit absence or underdevelopment of the fingernails and/or toenails and/or webbing between the fingers and/or toes (syndactyly).
Some affected infants may exhibit additional skeletal abnormalities including deformity of the pelvis (pelvic dysplasia), dislocation of both (bilateral) hips, lack of sternal ossification, slender ribs or bone fractures.
Additional findings that may be associated with Yunis-Varon syndrome include abnormalities of the heart such as cardiomyopathy or congenital heart defects.
In some children, urinary tract abnormalities may occur, including abnormal placement of the urinary opening (meatus) on the underside of the penis (hypospadias), failure of the testes to descend into the scrotum (cryptorchidism) and micropenis.
Additional findings have been reported in individuals with Yunis-Varon syndrome including central nervous system abnormalities and hypodontia.
What are the causes for yunis varon syndrome?
Yunis-Varon syndrome is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits a changed gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Some cases of Yunis-Varon syndrome have occurred among children who had parents who were related by blood (consanguineous). All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same non-working gene, which increases the risk to have children with a recessive genetic disorder.
The gene causing Yunis-Varon syndrome in some families was identified as FIG4. FIG4 codes for a protein regulating the transport of vesicles inside cells by modifying molecules called phosphoinositides. Different mutations in FIG4 can also cause Charcot-Marie-Tooth disease, a condition where the peripheral nerves lose their proper function, and polymicrogyria, a condition with brain malformations. Some researchers thought that mutations in FIG4 could also predispose mutation carriers to ALS (amyotrophic lateral sclerosis) but subsequent larger studies did not support this finding.
Some researchers have speculated that Yunis-Varon syndrome may occur as a result of defects in lysosomal storage. Lysosomal storage diseases comprise a group of metabolic disorders characterized by an abnormal build-up of various toxic materials in the body’s cells as a result of enzyme deficiencies. These disorders affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. FIG4 is involved in regulating the transport of various vesicles, including lysosomes, which could help explain the findings suggestive of abnormal lysosomal function.
Mutations in the VAC14 gene have also been found to be associated with Yunis-Varon syndrome.
What are the treatments for yunis varon syndrome?
Specific therapies for individuals with Yunis-Varon syndrome are symptomatic and supportive. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat skeletal abnormalities (orthopedists), physical therapists, physicians who specialize in diagnosing and treating disorders of the heart (cardiologists), and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.
Physicians should closely monitor infants with Yunis-Varon syndrome to promptly detect any feeding or breathing difficulties associated with the disorder. Physicians may recommend preventive measures and/or institute immediate appropriate therapy. Treatment for feeding difficulties may include artificial feeding methods such as tube feeding, which administers food through a tube directly into the infant’s stomach, or intravenous feeding, in which essential nutrients are administered into a vein using a tube. Breathing difficulties, when severe and life-threatening, may require special measures such as the use of a special machine (ventilator) that supports breathing (artificial respiration).
What are the risk factors for yunis varon syndrome?
Yunis-Varon syndrome is an extremely rare inherited disorder that affects males and females in equal numbers. 25 cases from 19 families have been reported since the disorder’s initial description in the medical literature in 1980.
Is there a cure/medications for yunis varon syndrome?
Early intervention is important in Yunis-Varon syndrome. Special services that may be beneficial to affected children may include special remedial education, special social support, physical therapy, and other medical, social, and/or vocational services.
Genetic counseling is recommended for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.