Ruvalcaba syndrome is a rare inherited disorder characterized by short stature, abnormalities affecting the head and facial (craniofacial) area, mental retardation, skeletal malformations, and/or underdeveloped (hypoplastic) genitalia. Characteristic craniofacial features include an abnormally small head (microcephaly); an abnormally small, narrow nose; and down-slanting eyelid folds (palpebral fissures). Skeletal malformations may include fifth fingers that are permanently fixed in a bent position (clinodactyly) and/or abnormally short bones between the wrists and the fingers (metacarpals) and the ankles and toes (metatarsals), resulting in unusually small hands and feet. In addition, affected children may have abnormal side-to-side curvature of the spine (scoliosis) and/or unusual prominence of the breastbone (pectus carinatum). Ruvalcaba syndrome is inherited as an autosomal dominant genetic trait.
Symptoms and physical findings associated with Ruvalcaba syndrome vary from case to case. Affected individuals may have short stature, mental retardation, abnormalities of the head and facial (craniofacial) area, skeletal malformations, and/or abnormalities of the genitals.
Craniofacial abnormalities associated with Ruvalcaba syndrome include an abnormally small head (microcephaly); an oval face; downslanting eyelid folds (palpebral fissures); a small mouth (microstomia); a narrow, small nose, which, in some cases, may appear “beaked”; a narrow upper jaw bone (maxilla), and/or crowded teeth.
Children with Ruvalcaba syndrome also have skeletal malformations such as abnormally short arms and legs (limbs); prominent elbows; low-set thumbs; fifth fingers that are permanently fixed in a bent position (clinodactyly); and/or abnormally short bones between the wrists and the fingers (metacarpals) and the ankles and toes (metatarsals), resulting in small hands and feet. In addition, affected children may have abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis), a narrow chest, unusual prominence of the breast bone (pectus carinatum), limited extension of certain joints, and/or inflammation of the bone and cartilage in the spinal column (osteochondritis of the spine or Scheuermann’s disease).
In some cases, children with Ruvalcaba syndrome have underdeveloped (hypoplastic) genitalia. Affected males may experience failure of one or both testes to descend into the scrotum (cryptorchidism).
Children with Ruvalcaba syndrome may also have underdeveloped, “onion-like” areas of skin on the body and/or an unusually large darkened area around the nipples (areola). In some cases, affected children may have kidney (renal) abnormalities (e.g., abnormal position of the kidney) and/or protrusion of a portion of the intestines through an abnormal opening in the muscular wall of the abdomen into the groin area (inguinal hernia).
According to the medical literature, one individual with Ruvalcaba syndrome also experienced abnormal widening (dilatation) of cavities (ventricles) within the brain and accumulation of excessive cerebrospinal fluid in the skull (hydrocephalus) as well as Dandy-Walker malformation. Dandy-Walker malformation is a rare malformation of the brain characterized by an abnormally enlarged space at the back of the brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts of the brain. (For more information on these disorders, choose “hydrocephalus” and “Dandy Walker” as your search terms in the Rare Disease Database.)
Ruvalcaba syndrome is inherited as an autosomal dominant genetic trait. As of yet the malfunctioning gene has not been identified.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
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 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent 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 percent. The risk is the same for males and females.
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.
Ruvalcaba syndrome is a rare disorder that, in theory, affects males and females in equal numbers. Probably fewer than a dozen confirmed cases have been reported in the medical literature. Several cases of what were initially diagnosed as Ruvalcaba syndrome proved to be cases of two related disorders — trichorhinophalangeal syndrome type III and Hunter-McAlpine craniosynostosis syndrome. (For more information on these disorders, see the Related Disorders section below.) It is highly likely that some cases of Ruvalcaba syndrome may go unrecognized and remain undiagnosed, making it difficult to determine its true frequency in the general population.
The diagnosis of Ruvalcaba syndrome may be suspected based upon identification of characteristic physical features (e.g., microcephaly, characteristic facial abnormalities, skeletal malformations, etc.). The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and x-ray studies of the skeleton that reveal shortening of bones in the hands and feet (i.e., metacarpals, metatarsals, and phalanges).
The treatment of Ruvalcaba syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, specialists who diagnose and treat skeletal disorders (orthopedists) and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
Specific therapies for the treatment of Ruvalcaba syndrome are symptomatic and supportive. Various orthopedic techniques, including surgery, may be used to help treat and/or correct skeletal abnormalities. Additional therapeutic and/or supportive measures may be necessary in some cases.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Gorlin RJ, Cohen MMJr, Hennekam RCM. eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:104.
RECENT JOURNAL ARTICLES
Thomas Ja, Manchester DK, Prescott KE, Milner R, McGavran L, Cohen MM Jr. Hunter-McAlpine craniosynostosis associated with skeletal anomalies and interstitial deletion of chromosome 17q. Am J Med Genet. 1996;62:372-75.
Niikawa N, Kamei T. The Sugio-Kajii syndrome, proposed tricho-rhino-phalangeal syndrome type III. Am J Med Genet. 1986;24:759-60.
Hunter A. Ruvalcaba syndrome. Am J Med Genet. 1985;21:785-86. (Letter)
Bianchi E, Livieri C, Arico M, Cattaneo E, Podesta A, Beluffi G. Ruvalcaba syndrome: a case report. Europ J Pediatr. 1984;142:301-03.
Sugio Y, Kajii T. Ruvalcaba syndrome: autosomal dominant inheritance. Am J Med Genet. 1984;19:759-60.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Ruvalcaba Syndrome. Entry Number; 180870: Last Edit Date; 8/14/1996.
Ruvalcaba syndrome. Multiple Congenital Anomaly/ Mental Retardation (MCA/MR) Syndromes. nd. 2pp.