Penta X Syndrome is a rare chromosomal disorder that affects females. Females normally have two X chromosomes. However, in those with Penta X Syndrome, there are three additional (or a total of five) X chromosomes in the nuclei of body cells (pentasomy X). The condition is typically characterized by moderate to severe mental retardation, short stature, malformations of the skull and facial (craniofacial) region, and/or other physical abnormalities. Characteristic craniofacial malformations may include upslanting eyelid folds (palpebral fissures), a flat nasal bridge, malformed ears, a short neck with a low hairline, and/or other findings. Penta X Syndrome may also be characterized by abnormal deviation (clinodactyly) or permanent flexion (camptodactyly) of the "pinkies" or fifth fingers; heart and/or kidney defects; deficient development of the ovaries and uterus; and/or other physical findings. The disorder results from errors during the division of reproductive cells in one of the parents.
Penta X Syndrome is characteristically associated with growth delays before birth (prenatal growth deficiency); failure to grow and gain weight at the expected rate (failure to thrive) after birth; and short stature. In addition, infants and children with Penta X Syndrome typically have delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation) and are affected by moderate to severe mental retardation.
The disorder is also characterized by distinctive malformations of the skull and facial (craniofacial) region. These often include an unusually small head (microcephaly); a round face; upslanting eyelid folds (palpebral fissures); a flat nasal bridge; low-set, malformed ears; and/or a short neck with a low hairline. Some affected individuals also have additional eye (ocular) abnormalities, such as widely spaced eyes (ocular hypertelorism); vertical skin folds that may cover the eyes’ inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); and/or partial absence of tissue from the irides or the colored regions of the eyes (iris colobomas). Additional features reported in association with Penta X Syndrome have included abnormal, rudimentary outgrowths of tissue in front of the external ears (preauricular tags); a small jaw (micrognathia); thick lips; incomplete closure of the roof of the mouth (cleft palate); and/or other findings. In addition, dental abnormalities may be present, such as abnormal contact of the teeth of the upper jaw with those of the lower jaw (malocclusion); unusually shaped molars with large pulp spaces (taurodontism); and/or enamel defects, potentially resulting in premature loss of certain “baby” (deciduous or primary) teeth.
Females with Penta X Syndrome may also have various musculoskeletal defects, such as abnormal fusion of the forearm bones (radioulnar synostosis); narrow shoulders; and/or unusually small hands with abnormal deviation (clinodactyly) or permanent flexion (camptodactyly) of the fifth fingers. Additional findings may include overlapping toes; a foot deformity in which the sole is turned inward (metatarsus varus); and/or an abnormality in which the knees are unusually close together and the space between the ankles is increased (“knock knees” [genua valga]). Some affected females also have overflexion or bending (i.e., hyperflexion) or dislocations of multiple joints, including those of the fingers, wrists, shoulders, elbows, and/or hips. In addition, reports indicate that some affected individuals may have abnormal skin ridge patterns (dermatoglyphics) on the fingers and palms of the hands.
In some cases, Penta X Syndrome may be associated with certain structural malformations of the heart at birth (congenital heart defects). Such defects may include an abnormal opening in the fibrous partition (septum) that normally separates the two lower chambers of the heart (ventricular septal defect [VSD]); patent ductus arteriosus (PDA); and/or other malformations. In PDA, the channel that is present between the aorta and the pulmonary artery during fetal development fails to close after birth, leaving an abnormal opening between the arteries. (The pulmonary artery transports oxygen-depleted [deoxygenated] blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide takes place. The aorta is the main artery of the body that arises from the left ventricle and supplies oxygenated blood to body tissues.)
Some females with Penta X Syndrome also have certain kidney (renal) abnormalities, such as underdevelopment of the kidneys (renal hypoplasia), horseshoe kidney, and/or other findings. Horseshoe kidney is a congenital abnormality in which the two kidneys are joined at the base.
In some cases, affected females may also have an unusually small uterus, deficient development of the ovaries, and/or other abnormalities. In addition, delayed puberty has been reported in some instances.
Penta X Syndrome is a chromosomal disorder characterized by the presence of three extra X chromosomes. Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair that normally consists of an X and a Y chromosome for males and two X chromosomes for females. Therefore, females with a normal chromosomal make-up (karyotype) have 46 chromosomes, including two X chromosomes (46,XX karyotype); they receive one chromosome from the mother and one from the father in each of the 23 pairs.
However, females with Penta X Syndrome have 49 chromosomes, five of which are X chromosomes (49,XXXXX karyotype). The presence of the three additional X chromosomes results from errors during the division of reproductive cells in one of the parents (nondisjunction during meiosis). Evidence suggests that the extra X chromosomes are typically derived from the mother. In addition, researchers indicate that the risk of such errors may increase with advanced parental age.
Penta X Syndrome is a rare chromosomal disorder that affects only females. Since the syndrome was originally described in 1963 (Kesaree N), over 20 cases have been reported in the medical literature. Some females with Penta X Syndrome were originally thought to be affected by Down Syndrome due to the presence of certain features sometimes associated with the latter disorder. (For further information, please see the “Related Disorders” section of this report below.)
Penta X Syndrome is diagnosed based upon thorough clinical examination; detection of characteristic physical findings; and chromosomal analysis that confirms the presence of three extra X chromosomes in body cells. In some instances, the abnormality may be detected before birth (prenatally) based on chromosomal analysis following certain procedures, such as amniocentesis or chorionic villus sampling (CVS). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta.
The treatment of Penta X Syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); heart specialists; and/or other health care professionals.
For some affected individuals, recommended treatment may include surgical correction of certain craniofacial, musculoskeletal, or other malformations associated with the disorder. In addition, for those with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be necessary. The specific surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.
Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also 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., craniofacial abnormalities, congenital heart defects, mental retardation].)
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