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NORD is very grateful to Lina Basel-Vanagaite, MD ,PhD, Director, Clinical Genetics Service, Schneider Children's Medical Center of Israel, for assistance in the preparation of this report.
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.
Yunis-Varon syndrome is an extremely 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 mental retardation.
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).
In some cases, 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 cases, 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 individual cases of Yunis-Varon syndrome including central nervous system abnormalities and hypodontia.
Yunis-Varon syndrome is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one 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 defective 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 normal genes from both parents and be genetically normal for that particular trait is 25%.
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 abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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. More research is necessary to determine whether defective lysosomal storage is involved in the development of Yunis-Varon syndrome.
The genetic basis of Yunis-Varon syndrome is currently unknown.
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. The characteristic physical findings associated with this disorder are obvious at birth (congenital).
Symptoms of the following disorders can be similar to those of Yunis-Varon syndrome. Comparisons may be useful for a differential diagnosis:
Cleidocranial dysplasia is a rare genetic disorder characterized by the association of the three following features: absence or severe underdevelopment (hypoplasia) of one or both of the collar bones (clavicles); delayed closure of the two soft openings (fontanels) on an infant's head with abnormal separation of the fibrous joints (sutures) that connect certain bones of the skull; and an abnormally large skull (macrocrania). Characteristic findings may include an unusually short, wide head (brachycephaly); dental abnormalities such as delayed growth (eruption) of both the "baby" and "adult" teeth; a short middle bone (phalanx) in the fifth fingers; abnormally short fingers (brachydactyly); and/or growth retardation, resulting in moderate short stature. Other physical findings may include a wide pelvic joint (pubic symphysis), and deformities of the spine such as abnormal side-to-side curvature of the spine (scoliosis), which may worsen (progress) with age. In some cases, affected infants may exhibit respiratory problems. Cleidocranial dysplasia is inherited as an autosomal dominant trait. (For more information on this disorder, choose "Cleidocranial Dysplasia" as your search term in the Rare Disease Database).
Mandibuloacral dysplasia is an extremely rare inherited disorder characterized by underdeveloped (hypoplastic) collarbones (clavicles); abnormally wide fibrous joints between certain bones of the skull (cranial sutures); joint stiffness; and an underdeveloped (hypoplastic) lower jaw (mandible) causing crowding of the teeth. Individuals with this disorder may also exhibit increased sensitivity to cold in the fingers as well as loss of bone tissue in the hands (acroosteolysis). In some cases, affected children may exhibit short stature, patchy loss of hair (alopecia), and/or degeneration (atrophy) of the skin on the hands and feet. Mandibuloacral dysplasia is thought to be inherited as an autosomal recessive trait.
Certain findings that may suggest a diagnosis of Yunis-Varon syndrome (e.g. limb and bone abnormalities or congenital heart defect) may be identified before birth (prenatally) using ultrasonography. In fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus. Yunis-Varon syndrome may be diagnosed or confirmed after birth based upon a thorough clinical evaluation, the identification of characteristic findings (e.g., hypoplastic claviculae, limb abnormalities, sparse hair, characteristic facial features).
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).
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 will be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., respiratory and heart problems, skeletal dysplasia, craniofacial deformities, etc.].)
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Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mandibuloacral Dysplasia with Type A Lipodystrophy: MADA. Entry No: 248370. Last Edited February 22, 2012. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed March 6, 2012.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Cleidocranial Dysplasia with Micrognathia, Absent Thumbs, and Distal Aphalangia. Entry No: 216340. Last Edited November 25, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed March 6, 2012.
Report last updated: 2012/03/07 00:00:00 GMT+0