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NORD is very grateful to Shashikant Kulkarni, PhD, Director of CytoGenomics and Molecular Pathology, Director of Clinical & Molecular Cytogenetics, Department of Pathology, Washington University School of Medicine, for assistance in the preparation of this report.
Chromosome 15, Distal Trisomy 15q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of the 15th chromosome (15q) appears three times (trisomy) rather than twice in cells of the body. The disorder is characterized by growth delays before and/or after birth (prenatal and/or postnatal growth retardation); mental retardation; and/or distinctive malformations of the head and facial (craniofacial) area. Additional abnormalities typically include an unusually short neck; malformations of the fingers and/or toes; abnormal sideways curvature of the spine (scoliosis) and/or other skeletal malformations; genital abnormalities, particularly in affected males; and/or, in some cases, heart (cardiac) defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. In most cases, Chromosome 15, Distal Trisomy 15q is due to a chromosomal balanced translocation in one of the parents.
In individuals with Chromosome 15, Distal Trisomy 15q, an extremely rare chromosomal disorder, the end (distal) portion of the long arm (q) of chromosome 15 (15q) is duplicated (trisomic). Symptoms and physical characteristics associated with the disorder may vary in range and severity, depending upon the exact size and location of the duplicated portion of chromosome 15q.
In some cases, Chromosome 15, Distal Trisomy 15q may be characterized by abnormally slow growth before and/or after birth (prenatal and/or postnatal growth retardation) . In addition, many affected infants experience swallowing and feeding difficulties that may be due to the presence of certain malformations of the head and facial (craniofacial) area. Such feeding and swallowing difficulties may result in or contribute to an affected infant's failure to grow or gain weight at the expected rate (failure to thrive). However, in certain rare cases (i.e., trisomy 15q25-qter), affected individuals may exhibit abnormally tall stature. (For more information on trisomy 15q25-qter, see the "Causes" section below.)
Most infants with Chromosome 15, Distal Trisomy 15q also exhibit abnormally diminished muscle tone (hypotonia). In addition, most affected infants and children have severe to profound mental retardation. However, in rare cases (i.e., trisomy 15q25-qter), only mild mental retardation may be present.
Many infants and children with the disorder have characteristic malformations of the head and facial (craniofacial) area. In some cases, the fibrous joints between certain bones in the skull (sagittal sutures) close prematurely (craniosynostosis), causing the head to appear abnormally long and narrow (dolichocephaly). In addition, in many cases, the head may appear abnormally small (microcephaly), with abnormal bulging (prominence) of the back of the head (occiput) and a sloping forehead. In addition, the face may appear dissimilar from one side to the other (facial asymmetry). In rare cases (i.e., trisomy 15q25-qter), affected infants may have hydrocephalus, a condition characterized by inhibition of the normal flow of cerebrospinal fluid (CSF) within and abnormal widening (dilatation) of the cerebral spaces of the brain (ventricles), causing accumulation of CSF in the skull and potentially increased pressure on brain tissue.
Additional craniofacial malformations typically associated with the disorder may include downwardly slanting, short, and/or narrow eyelid folds (palpebral fissures); drooping of the upper eyelids (ptosis); an abnormally large, prominent, and/or rounded (bulbous) nose with a broad nasal bridge; and/or an unusually small, triangular mouth. In addition, many affected infants and children may have an abnormally long groove in the upper lip (philtrum), a crease in the center (midline) of the lower lip, a highly arched roof of the mouth (palate), an unusually small jaw (micrognathia), and/or abnormally round, "puffy" cheeks. In some cases, the ears may be abnormally large, low-set, and/or malformed (dysplastic). In addition, the neck may be short and/or webbed, which, in some cases, may be due to malformations of certain bones in the upper portion of the spine (cervical vertebrae). Approximately one third of affected infants and children may also experience episodes of uncontrolled electrical disturbances in the brain (seizures).
In addition, most infants and children with Chromosome 15, Distal Trisomy 15q have skeletal abnormalities affecting the fingers, toes, chest (thorax), and/or spine. Affected individuals may have unusually long, thin fingers and/or toes (arachnodactyly), permanently flexed fingers (camptodactyly), and/or excessive extension (hyperextension) of the thumbs. In addition, the joints of the hands and feet may become fixed in a permanently flexed position (joint contractures). Affected individuals may also have side-to-side curvature of the spine (scoliosis) and/or abnormal depression of the sternum, the bone forming the center of the chest ("funnel chest" or pectus excavatum).
In many cases, individuals with Chromosome 15, Distal Trisomy 15q also have genital abnormalities. In males, such abnormalities may include failure of the testes to descend into the scrotum (cryptorchidism) and/or low levels of testicular function (hypogonadism), resulting in delayed development of secondary sexual characteristics (i.e., deepening of the voice, characteristic hair growth patterns, sudden increase in growth and development of the testes and scrotum, etc.). Some affected females may exhibit underdevelopment of the two long folds of skin on either side of the vaginal opening (labia majora).
In addition, many affected infants may have abnormalities of the heart (congenital heart defects) and/or may exhibit an increased susceptibility to recurrent respiratory tract infections. In some cases, swallowing and feeding difficulties may cause food to be inhaled (aspirated) into the lungs, which may result in severe lung infections (aspiration pneumonia). In some cases, such abnormalities may result in life-threatening complications.
Chromosome 15, Distal Trisomy 15q is an extremely rare chromosomal disorder in which the end (distal) portion of the long arm (q) of the 15th chromosome appears three times (trisomy) rather than twice in cells of the body. Chromosomes are found in the nucleus of all body cells except red blood cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered. For example, "15q21" refers to band 21 on the long arm of chromosome 15.
The duplication of the distal portion of chromosome 15q is responsible for the symptoms and physical features that characterize this disorder. The range and severity of associated abnormalities may depend upon the exact length and location of the duplicated portion of chromosome 15q.
According to investigators, in those with Chromosome 15, Distal Trisomy 15q, the duplicated portion of 15q usually begins between bands 15q21 and 15q23 (breakpoint) and extends toward the end or "terminal" portion of chromosome 15q (qter). In rare cases, the breakpoint has occurred at band 15q25. According to the medical literature, although individuals with trisomy 15q25-qter have many of the characteristic abnormalities typically associated with the disorder, there may be some differences. (For further information, please see the "Symptoms" section above.) A few families have also been described in which the breakpoint has occurred at band 15q15.
In most cases, Chromosome 15, Distal Trisomy 15q is due to a chromosomal "balanced translocation" in one of the parents. Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. A translocation is balanced if it consists of an altered but balanced set of chromosomes. If a chromosomal rearrangement is balanced, meaning that it consists of an altered but balanced amount of genetic material, it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of unbalanced chromosome inheritance in the carrier's offspring. Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude a chromosomal rearrangement in one of the parents.
According to the medical literature, in the case of parental balanced translocations that result in Distal Trisomy 15q, the second chromosome involved with chromosome 15q has varied from case to case; however, symptoms and findings characteristically associated with the disorder (clinical phenotype) appear consistent.
Chromosome 15, Distal Trisomy 15q is an extremely rare chromosomal disorder that is thought to affect males approximately twice as often as females. Since the disorder was originally described in the medical literature in 1974 (A. Fujimoto), more than 30 cases have been reported in the literature. The majority of symptoms and physical features associated with the disorder are apparent at birth.
Other chromosomal disorders may be characterized by prenatal and postnatal growth retardation, mental retardation, distinctive craniofacial abnormalities, genital malformations, congenital heart defects, and/or other abnormalities similar to those potentially associated with Chromosome 15, Distal Trisomy 15q. Chromosomal testing is necessary to confirm the specific chromosomal abnormality present. (For further information on such disorders, choose the name of the specific chromosomal disorder in question or use "chromosome" as your search term in the Rare Disease Database.)
In some cases, the diagnosis of Chromosome 15, Distal Trisomy 15q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS) Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may reveal the presence of Distal Trisomy 15q.
Chromosome 15, Distal Trisomy 15q may also be diagnosed and/or confirmed after birth (postnatally) based upon a thorough clinical evaluation, identification of characteristic physical findings, and chromosomal studies.
Certain specific abnormalities that may occur in association with Distal Trisomy 15q may be detected and/or confirmed by specialized imaging studies and/or additional tests. For example, specialized x-ray studies may be used to confirm and/or characterize certain skeletal abnormalities potentially associated with the disorder (e.g., dolichocephaly, micrognathia, cervical vertebral abnormalities, scoliosis). Congenital heart defects potentially associated with Chromosome 15, Distal Trisomy 15q may be detected, confirmed, and/or characterized by a thorough clinical evaluation and specialized tests that allow physicians to evaluate the structure and function of the heart (e.g., x-ray studies, electrocardiogram [EKG] echocardiogram, cardiac catherization). In addition, in some cases, electroencephalography (EEG), which records the brain's electrical impulses, may reveal brain wave patterns that are characteristic of certain types of seizure activity.
The treatment of Chromosome 15, Distal Trisomy 15q is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who specialize in diagnosing and treating disorders of the skeletal system (orthopedists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
The treatment of Chromosome 15, Distal Trisomy 15q may include surgical repair of certain malformations. In some cases, surgery may be performed to correct congenital heart defects, craniofacial malformations, webbing of the neck, flexion contractures, abnormalities of the hands and/or feet, genital malformations, and/or other abnormalities that may be associated with the disorder. The surgical procedures performed will depend upon the severity and location of the anatomical abnormalities and their associated symptoms.
In some cases, abnormalities involving the joints, tendons, muscles, and bones (e.g., flexion contractures, malformations of the fingers and/or toes, scoliosis) may be treated with orthopedic techniques potentially in combination with surgery. Physical therapy may also be prescribed to help improve coordination of movements (mobility).
In addition, physicians may recommend preventive measures for affected infants and children who may be prone to repeated respiratory infections. Physicians may also regularly monitor affected individuals for such infections to ensure early detection and appropriate, prompt treatment.
Early intervention is important to ensure that children with Chromosome 15, Distal Trisomy 15q reach their potential. Special services that may be beneficial to affected children may include special remedial education, special social support, and/or other medical, social, and/or vocational services.
Genetic counseling will be of benefit for families of children with Chromosome 15, Distal Trisomy 15q. Chromosomal studies are necessary to determine whether a balanced translocation is present in one of the parents. Other treatment for the disorder is symptomatic and supportive.
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Report last updated: 2009/04/10 00:00:00 GMT+0