Chromosome 9, Trisomy 9p (Multiple Variants)
Synonyms of Chromosome 9, Trisomy 9p (Multiple Variants)
- Chromosome 9, Complete Trisomy 9P
- Chromosome 9, Partial Trisomy 9P, Included
- Chromosome 9, Trisomy 9pter-q11-13, Included
- Chromosome 9, Trisomy 9pter-q22-32, Included
- Dup(9p) Syndrome
- Duplication 9p Syndrome
- Rethore Syndrome (obsolete)
- Trisomy 9P Syndrome (Partial), Included
- No subdivisions found.
This disease entry was made possible due to the generosity of the Robert Lee and Clara Guthrie Patterson Trust, through grant funds provided for the National Organization for Rare Disorders' "Pediatric Rare Disease Database Project."
Chromosome 9, Trisomy 9p is a rare chromosomal syndrome in which a portion of the 9th chromosome appears three times (trisomy) rather than twice in cells of the body. The trisomy may involve a portion of the short arm (9p), the entire short arm, or the short arm and a portion of the long arm (9q) of chromosome 9. (Each chromosome contains a short arm known as "p" and a long arm designated as "q.") Evidence suggests that, in many cases, associated symptoms and findings may be relatively similar among affected infants despite differing lengths of the trisomic (duplicated) segment of 9p. However, in those with larger trisomies (e.g., extending to middle or end [distal] regions of 9q), additional features may also be present that appear to correlate with the extent of the duplication.
Virtually all individuals with Trisomy 9p are affected by mental retardation and distinctive malformations of the skull and facial (craniofacial) region. In some instances, additional physical abnormalities may also be present, such as other skeletal defects, structural malformations of the heart that are present at birth (congenital heart defects), and/or other findings. In some cases, the trisomy appears to result from a balanced chromosomal rearrangement in one of the parents; in others, it is thought to arise from spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically).
Chromosome 9, Trisomy 9p is often characterized by low muscle tone (hypotonia) as well as growth deficiency and delayed bone maturation, with associated short stature. Growth retardation primarily begins after birth (postnatally). However, reports indicate that, in those with larger trisomic segments (e.g., through bands 9q22 or 9q32), growth deficiency may begin before birth (intrauterine growth retardation). (For further information, please see the "Causes" section below.)
In virtually all cases, Trisomy 9p is also associated with varying degrees of mental retardation, ranging from moderate to severe, and delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation). According to reports in the medical literature, language development appears to be most severely delayed.
Many infants and children with Trisomy 9p also have a characteristic facial appearance due to distinctive craniofacial malformations. Such abnormalities may include an unusually small head (microcephaly) that may be short and broad (brachycephaly); a wide mouth with downturned corners; a prominent, relatively bulbous nose; large, low-set, "cup-shaped" ears; and/or an abnormally short vertical groove in the center of the upper lip (philtrum). Characteristic eye abnormalities may also be present, such as deeply set, widely spaced eyes; downwardly slanting eyelid folds (palpebral fissures); vertical skin folds that may cover the eyes' inner corners (epicanthal folds); and/or abnormal deviation of one eye in relation to the other (strabismus). Some affected infants may also have a "worried" look; a short, webbed neck; a highly arched roof of the mouth (palate); and/or widely spaced nipples. In addition, in those with larger trisomic segments, additional craniofacial features may include an abnormally small jaw (micrognathia), incomplete closure (clefting) of the palate (cleft palate), and/or an abnormal groove in the upper lip (cleft lip).
Many individuals with Trisomy 9p may also have various abnormalities of the hands and feet. These may include decreased length of certain bones of the fingers and toes (phalanges) and within the hands and feet (metacarpals and metatarsals); short fingers and toes (digits) with small nails; and/or abnormal flexion or bending (clinodactyly) of the "pinkies" or fifth fingers. The syndrome may also be associated with unusual, distinctive skin ridge patterns of the fingers and hands (abnormal dermatoglyphics), including a single crease across the palms; a single flexion crease on the fifth fingers; a reduced total finger ridge count; and/or other findings.
In some cases, Trisomy 9p may be associated with additional skeletal defects. Such abnormalities may include delayed closure of the "soft spots" (fontanels) and the fibrous joints (cranial sutures) between certain bones of the skull; a deformity in which the foot is twisted out of shape or position (clubfoot); and/or abnormal curvature of the spine that may develop during the second decade of life. Less commonly, additional skeletal abnormalities may include partial webbing (syndactyly) of certain fingers and toes, dislocation of the hips at birth, and/or other abnormalities.
Approximately five to 25 percent of children with Chromosome 9, Trisomy 9p may also have congenital heart defects, particularly an abnormal opening in the partition (septum) that separates the two lower chambers (ventricles) of the heart (ventricular septal defects [VSDs]). In those with cardiac defects, associated symptoms and findings may vary, depending upon the size, nature, and/or combination of heart malformations present and other factors. For example, in some cases, such as those with small isolated VSDs, no symptoms may be apparent (asymptomatic). However, in other instances, such as those with larger VSDs and/or other cardiac defects, associated symptoms and findings may include difficulties feeding, shortness of breath, profuse sweating, irritability, easy fatigability, bluish discoloration of the skin and mucous membranes (cyanosis), and/or other abnormalities. In severe cases, congenital heart disease may lead to potentially life-threatening complications.
In some instances, additional physical abnormalities have been reported in association with Trisomy 9p. These have included genital malformations in affected males, such as a small penis (micropenis), undescended testes (cryptorchidism), and/or abnormal placement of the urinary opening (hypospadias); kidney (renal) malformations; protrusion of part of the intestine and the fold of fatty membrane in front of the intestine (omentum) through a defect in the abdominal wall at the navel (umbilical hernia); and/or hydrocephalus. The latter refers to obstructed flow or impaired absorption of cerebrospinal fluid (CSF), resulting in abnormal accumulation of CSF, usually under increased pressure. CSF is the watery protective fluid that circulates through the cavities (ventricles) of the brain, the canal containing the spinal cord (spinal canal), and the space between layers of the protective membranes (meninges) surrounding the brain and spinal cord (i.e., subarachnoid space). Depending upon the age at symptom onset and other factors, associated symptoms may include rapid enlargement of the head, sudden episodes of uncontrolled electrical activity in the brain (seizures), irritability, vomiting, headache, loss of coordination, deteriorating mental functioning, and/or other findings. In severe cases, potentially life-threatening complications may result.
In individuals with Chromosome 9, Trisomy 9p, all or a portion of the short arm (p) of chromosome 9 (9p) appears three times (trisomy) rather than twice in the cells of the body. In addition, in some cases, a portion of the long arm of chromosome 9 (9q) may also be trisomic (duplicated). 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 of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p," a long arm identified by the letter "q," and a narrowed region at which the two arms are joined (centromere). Chromosomes are further subdivided into bands that are numbered outward from the centromere. For example, the short arm of chromosome 9 includes bands 9p11 to 9p24, and the long arm includes bands 9q11 to 9q34.
Evidence indicates that, in many cases, clinical features may be relatively similar among affected individuals despite differing lengths of the duplicated segment of 9p. According to some researchers, such findings suggest that certain characteristic abnormalities associated with the syndrome may result from trisomy of the end (distal) portion of 9p. ("Distal" indicates away or farthest from a particular point of reference, meaning the chromosome's centromere. The distal region of 9p is sometimes referred to as "9p2" and includes bands 9p21 through 9p24, the latter of which is the end or "terminal" band of 9p [also known as "9pter"].) However, in individuals with larger trisomies, such as those that extend through bands 9q22 or 9q32, additional clinical findings may also be present that appear to correlate with the extent of the duplication.
Generally, according to investigators, trisomies involving part or all of 9p and, in some cases, extending to 9q11-13 may be characterized by mental retardation and distinctive craniofacial malformations. However, in addition to such features, congenital heart defects, other skeletal abnormalities (e.g., congenital hip dislocation), intrauterine growth retardation, and additional craniofacial malformations (e.g., micrognathia, cleft lip and cleft palate) are more common with trisomies extending to band 9q22-q32. (Evidence indicates that larger trisomies involving more of 9q are associated with features characteristic of Chromosome 9, Trisomy Mosaic; for more information, please see the "Related Disorders" section of this report below.)
In approximately 50 percent of cases, Chromosome 9, Trisomy 9p may be due to a balanced chromosomal rearrangement in one of the parents. In most cases, the parental rearrangement is a "balanced translocation." Translocations occur when portions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. If a chromosomal rearrangement is balanced, meaning that it consists of an altered but balanced set of chromosomes, it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrier's offspring.
Rare cases have also been reported in which the parental chromosomal rearrangement has been an inversion. An inversion is characterized by breakage of a chromosome in two places and reunion of the segment in the reverse order.
The remaining cases have appeared to result from spontaneous (de novo) errors very early in embryonic development. In such de novo cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.
Chromosomal analysis and genetic counseling are typically recommended for parents of an affected child to help confirm or exclude the presence of a balanced translocation or other chromosomal rearrangement involving chromosome 9 in one of the parents.
In observed cases, Chromosome 9, Trisomy 9p has appeared to affect females approximately twice as frequently as males. The chromosomal abnormality was originally reported in 1970; Trisomy 9p was proposed as a distinct syndrome with characteristic symptoms and findings in 1975. More than 100 cases have since been reported in the medical literature.
Symptoms of the following disorders may be similar to those of Chromosome 9, Trisomy 9p. Comparisons may be useful for a differential diagnosis:
Chromosome 9, Tetrasomy 9p is a rare chromosomal disorder in which the short arm of chromosome 9 (9p) is present four times (tetrasomy) rather than twice in all or some cells of the body. Although many associated symptoms and findings may be similar to those seen in individuals with Trisomy 9p, researchers suggest that such features may be more variable or severe in some cases. Characteristic abnormalities associated with Tetrasomy 9p may include growth deficiency; psychomotor retardation; moderate to severe mental retardation; and various craniofacial, skeletal, heart (cardiac), kidney (renal), and/or other physical defects. Craniofacial abnormalities may resemble those associated with Trisomy 9p, such as an unusually small head (microcephaly); a bulbous nose; low-set, malformed ears; a downslanted mouth; deeply set, widely spaced eyes; a short neck; and/or other features. Chromosome 9, Tetrasomy 9p appears to result from spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically). (For more information, choose "Tetrasomy 9p" as your search term in the Rare Disease Database.)
Chromosome 9, Trisomy Mosaic is a rare chromosomal disorder characterized by trisomy of the entire 9th chromosome in some cells of the body (mosaicism). The term "mosaicism" indicates that a percentage of an affected individual's cells has the chromosomal abnormality, while other cells may have a normal chromosomal makeup. The range and severity of associated symptoms and findings may depend on the percentage of cells with the extra chromosome. Characteristic features may include growth deficiency before birth (intrauterine growth retardation); congenital heart defects; skeletal, genital, renal, and/or neurologic abnormalities; and/or variable craniofacial defects, such as a small head, a bulbous nose, short eyelid folds (palpebral fissures), deeply set eyes, a small jaw (micrognathia), low-set and malformed ears, a short neck, and/or other abnormalities. Chromosome 9, Trisomy Mosaic may be caused by errors during the division of a parent's reproductive cells (meiosis) or during the division of body tissue cells (somatic cells) early in the development of the embryo (mitosis); the reason for such errors is not known. (For more information on this disorder, choose "Chromosome 9, Trisomy Mosaic" as your search term in the Rare Disease Database.)
Additional chromosomal disorders may be characterized by symptoms and findings similar to those associated with Chromosome 9, Trisomy 9p. 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 9, Trisomy 9p may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves create an image of the developing fetus, potentially revealing certain characteristic findings that suggest a chromosomal disorder or other developmental abnormalities. 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. Chromosomal studies performed on such fluid or tissue samples may reveal trisomy of part or all of the short arm of chromosome 9 (9p) and, in some cases, a portion of the long arm (9q).
Chromosome 9, Trisomy 9p may also be diagnosed and/or confirmed after birth (postnatally) by a thorough clinical evaluation, identification of characteristic physical findings, chromosomal analysis, and other specialized tests.
In some cases, diagnostic evaluation may include enzyme tests to detect elevated activity of the galactose-1-phosphate uridyltransferase (GALT) enzyme or the nucleoside triphosphate adenylatekinase (AK3) enzyme, both of which are known to be regulated by genes on the short arm of chromosome 9. In addition, in those diagnosed with Trisomy 9p, various specialized tests may be performed to help detect and/or characterize certain abnormalities (e.g., certain skeletal malformations, congenital heart defects, etc.) that may be associated with the syndrome.
The treatment of Chromosome 9, Trisomy 9p is directed toward the specific symptoms and physical findings 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 abnormalities of the skeleton, joints, muscles, and related tissues (orthopedists); physicians who specialize in heart abnormalities (cardiologists); neurologists; and/or other health care professionals.
For affected individuals with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be required. In addition, in some cases, physicians may recommend surgical repair or correction of certain craniofacial malformations, additional skeletal abnormalities, genital defects, hernias, renal anomalies, and/or other malformations associated with the disorder. The specific surgical procedures performed will depend upon the nature and severity of the anatomical abnormalities, their associated symptoms, and other factors.
Early intervention services may also be important in ensuring that affected children reach their potential. Special services that may be beneficial include special remedial education, speech therapy, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for families of affected children. 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:
Toll free: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Chromosome 9, Trisomy 9p (Multiple Variants) Resources
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., mental retardation, craniofacial abnormalities, congenital heart defects, etc.].)
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