Chromosome 9, Trisomy 9p (Multiple Variants)

Chromosome 9, Trisomy 9p (Multiple Variants)

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Chromosome 9, Trisomy 9p (Multiple Variants) is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Trisomy 9P Syndrome (Partial), Included
  • Chromosome 9, Partial Trisomy 9P, Included
  • Chromosome 9, Complete Trisomy 9P
  • Rethore Syndrome (obsolete)
  • Duplication 9p Syndrome
  • Dup(9p) Syndrome
  • Chromosome 9, Trisomy 9pter-q11-13, Included
  • Chromosome 9, Trisomy 9pter-q22-32, Included

Disorder Subdivisions

  • None

General Discussion

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).

Symptoms

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.

Causes

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.

Affected Populations

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.

Standard Therapies

Diagnosis

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.



Treatment

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.

Investigational Therapies

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

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:50-54.



Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:82-84.



Buyse ML. Birth Defects Encyclopedia. Dover, Mass: Blackwell Scientific Publications, Inc; 1990:354-56.



JOURNAL ARTICLES

Roberts DJ, et al. Characteristics of structural heart defects in trisomy 9 and their relationship to those in trisomy 13, 18, and 21. Am Heart J. 1993;125:1681-90.



Bussani Mastellone C, et al. Four cases of trisomy 9p syndrome with particular chromosome rearrangements. Ann Genet. 1991;34:115-19.



Nakamura Y, et al. Abnormal chromosome 9 in a neonate program. Report of three cases. Arch Pathol Lab Med. 1990;114:185-87.



Wilson GN, et al. The phenotypic and cytogenetic spectrum of partial trisomy 9. Am J Med Genet. 1985;20:277-82.



Shih LY, et al. Gene dosage studies supporting localization of the structural gene for galactose-1-phosphate uridyl transferase (GALT) to band p13 of chromosome 9. Am J Med Genet. 1984;19:539-43.



Steinbach P, et al. Demonstration of gene dosage effects for AK3 and GALT in fibroblasts from a fetus with 9p trisomy. Hum Genet. 1983;63:290-91.



Drusini A, et al. Dermatoglyphic pattern of the 9p syndrome. Acta Anthropogenet. 1983;7:241-47.



Schinzel A. Trisomy 9p, a chromosome aberration with distinct radiologic findings. Radiology. 1979;130:125-33.



Sandig KR, et al. Trisomy 9p resulting from de novo 9/15 translocation and a 9p isochromosome. Hum Genet. 1979;52:175-78.



Fryns JP, et al. Partial duplication of the short arm of chromosome 9 (p13 leads to p22) in a child with typical 9p trisomy phenotype. Hum Genet. 1979;46:231-35.



Centerwall WR, et al. Familial 'partial 9p' trisomy: six cases and four carriers in three generations. J Med Genet. 1976;13:57-61.



Schinzel A, et al. Trisomy 9p due to paternal translocation, t(9;13) (q13;q12). Humangenetik. 1975;30:307-16.



Centerwall WR, et al. The trisomy 9p syndrome. Pediatrics. 1975;56:748-55.



Jacobsen P, et al. Trisomy 9p in a patient with a de novo 9/15 translocation. Clin Genet. 1975;7:317-24.



Rethore MO, et al. Four cases of trisomy for the short arm of chromosome 9. Individualization of a new morbid entity. Ann Genet. 1970;13:217-32.

Resources

Support Organization for Trisomy 18, 13, and Related Disorders

2982 S. Union Street

Rochester, NY 14624-1926

Fax: (585)594-1957

Tel: (800)716-7638

Email: barbv@trisomy.org

Internet: http://www.trisomy.org



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



AmeriFace

P.O. Box 751112

Limekiln, PA 19535

USA

Tel: (702)769-9264

Fax: (702)341-5351

Tel: (888)486-1209

Email: info@ameriface.org

Internet: http://www.ameriface.org



Trisomy 9 International Parent Support (9TIPS)

4027 E. Piedmont Drive

Highland, CA 92346

USA

Tel: (909)862-4470

Email: atoddna@sprynet.com

Internet: http://www.trisomy9.org/9tips.htm



American Heart Association

7272 Greenville Avenue

Dallas, TX 75231

Tel: (214)784-7212

Fax: (214)784-1307

Tel: (800)242-8721

Email: Review.personal.info@heart.org

Internet: http://www.heart.org



Support Organization for Trisomy 13/18 and Related Disorders, UK

c/o Christine Rose

48 Froggatts Ride

Walmley

Sutton Coldfield

West Midlands, B76 2TQ SOFT

United Kingdom

Tel: 01213513122

Email: enquiries@soft.org.uk

Internet: http://www.soft.org.uk



UNIQUE - Rare Chromosome Disorder Support Group

P.O. Box 2189

Caterham

Surrey, CR3 5GN

United Kingdom

Tel: 4401883330766

Fax: 4401883330766

Email: info@rarechromo.org

Internet: http://www.rarechromo.org



Craniofacial Foundation of America

975 East Third Street

Chattanooga, TN 37403

Tel: (423)778-9176

Fax: (423)778-8172

Tel: (800)418-3223

Email: terry.smyth@erlanger.org

Internet: http://www.craniofacialfoundation.org



Support Organisation for Trisomy and Related Disorders

Email: mandyjc@amnet.net.au

Internet: http://www.trisomy9.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

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