Years published: 1996, 2001, 2003, 2018, 2023
NORD gratefully acknowledges Janette DiMonda, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program, Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, and Deborah A. Bruns, PhD, Professor, Special Education Program, School of Education, Southern Illinois University Carbondale, for assistance in the preparation of this report.
Mosaic trisomy 9 is a rare chromosomal disorder in which the entire 9th chromosome appears three times (trisomy) rather than twice in some cells of the body. The term “mosaic” indicates that some cells contain the extra chromosome 9, while others have the typical chromosomal pair. Mosaic trisomy 9 may be caused by errors during the division of a parent’s egg or sperm or during the division of body tissue cells (somatic cells) early in the development of the fetus.
Associated symptoms and findings may vary greatly in range and severity, depending on the percentage of cells with the extra chromosome. However, common features include growth deficiency before birth (intrauterine growth restriction or IUGR); structural malformations of the heart that are present at birth (congenital heart defects); and/or distinctive differences in the shape of the skull and facial (craniofacial) region, such as a sloping forehead, a bulbous nose, short eyelid folds (palpebral fissures), deeply set eyes and/or low-set ears. The syndrome may also be characterized by musculoskeletal, genital, kidney (renal) and/or additional physical anomalies. Intellectual disability is common and varies in severity.
As noted above, mosaic trisomy 9 is characterized by an extra 9th chromosome (trisomy 9) in some cells of the body (mosaicism). The range and severity of associated features is variable depending on the percentage of cells in the body with an extra chromosome 9 (trisomic cells). In addition, rare cases have also been reported in which all body cells have appeared to be trisomic for all of chromosome 9; such “nonmosaic” cases are sometimes referred to as full trisomy 9 syndrome. According to investigators, in such patients, characteristic clinical features and affected organs may not substantially differ from those seen with trisomy 9 mosaicism. However, symptoms and findings associated with the latter may tend to be less severe in some cases due to the percentage of cells with an extra chromosome 9. Results of testing for mosaicism can also vary depending on the type of sample (e.g., blood, saliva) and age of the individual.
Mosaic trisomy 9 is generally characterized by growth deficiency beginning prenatally (IUGR), failure to gain height and weight at the expected rate during infancy (failure to thrive), and low muscle tone (hypotonia). Most infants and children with mosaic trisomy 9 have feeding difficulties and may require a feeding tube to supplement oral feeding or for all nutritional intake.
Many affected individuals have intellectual disability characterized by delays in learning academic as well as functional/daily living skills. However, there have also been some reports in which individuals with the disorder exhibit typical psychomotor development (e.g., walking unaided) or only mild gross motor delay. Regression of skills is uncommon. Recent reports indicate that affected individuals possess strengths in language and communication development (particularly receptive speech, or their ability to understand language expressed to them) as well as social-emotional development.
Individuals diagnosed with mosaic trisomy 9 exhibit specific differences in their facial features and the shape of their skull. Many affected infants have a small head size (microcephaly); a sloping forehead with narrow temples; a broad nose with a bulbous tip and “slit-like” nostrils and/or a small jaw (micrognathia). Additional characteristic features may include wideness of the “soft spots” (fontanels) and the fibrous joints (i.e., cranial sutures) between certain bones of the skull; a prominent upper lip covering a receding lower lip; a highly arched roof of the mouth (palate); low-set, unusually shaped ears and/or a short neck. Various eye (ocular) anomalies may also be present, such as short, upwardly slanting eyelid folds (palpebral fissures); deeply set eyes; reduction in the size of the eyes (microphthalmia); clouded corneas and/or other ocular defects that can impact vision. Some affected infants may also have a groove in the upper lip (cleft lip); incomplete closure of the palate (cleft palate); outgrowths of skin and cartilage on or before the ears (preauricular tags) and/or other craniofacial differences. Some individuals have been reported to have hearing loss requiring ear tubes or hearing aids.
Previous studies have estimated that approximately 65% of affected individuals have congenital heart defects, however more recent studies report lower numbers. The most common defects include an abnormal opening in the partition (septum) that separates the two lower or upper chambers (ventricles or atria) of the heart, called ventricular septal defects (VSDs) or atrial septal defects (ASDs). Other heart defects include patent ductus arteriosus (PDA) and/or other associated defects that allow some oxygen-rich blood to recirculate through the lungs and potentially lead to rising blood pressure in the lungs (pulmonary hypertension). Some individuals with mosaic trisomy 9 will have more than one heart defect.
In individuals with cardiac defects, associated symptoms and concerns may vary depending upon the size, nature, and/or combination of heart malformations present and other factors including age and respiratory function. Some individuals may show no apparent symptoms (asymptomatic), while others may develop difficulties in feeding, poor growth, difficult or labored breathing (dyspnea), profuse sweating, an impaired ability of the heart to pump blood efficiently to the lungs and other parts of the body (heart failure) and/or other problems. In severe cases, congenital heart disease may lead to potentially life-threatening complications. Individuals may require palliative or intensive surgery to correct cardiac defects. Recovery time varies.
Individuals with mosaic trisomy 9 may also experience respiratory issues including central and/or obstructive apnea. There are instances of short as well as long term need for oxygen (via nasal canula) and placement of a tracheotomy to assist with the airway. A sleep study is often utilized to identify specific respiratory needs. A bronchoscopy or similar procedure may be needed to determine anatomical anomalies affecting respiration. Nebulizer treatments may be needed as well as deep suctioning to assist with mucus build-up affecting breathing. It is critical to include a pulmonologist on the medical team if these concerns persist, especially when one or more cardiac defects is also present.
Mosaic trisomy 9 is also often characterized by conditions affecting muscles and bones including congenital dislocation of the hips (developmental dysplasia of the hip), atypical position and/or limited function of other joints, such as the elbows, knees and/or fingers and toes (digits) and atypical curvature of the spine. Underdevelopment (hypoplasia) of certain bones of the digits (phalanges); hypoplasia of the nails and/or a single crease across the palms (single transverse palmar crease) may also be present. Other skeletal differences have also been reported including a narrow chest, rib defects and differences in shape of specific bones of the spine (vertebral anomalies).
Affected males may also have genital complications including undescended testes (cryptorchidism), a small penis (micropenis) and/or atypical placement of the urinary opening (hypospadias, such as on the underside of the penis. Kidney (renal) complications may also be present in both males and females, including renal cysts, swelling (distension) of the kidneys with urine (hydronephrosis) due to narrowing or blockage of the tubes (i.e., ureters) that carry urine from the kidneys into the bladder and/or additional renal problems.
In some cases, mosaic trisomy 9 may also be associated with brain anomalies such as hydrocephalus, Dandy-Walker malformation and/or other features. Hydrocephalus involves excess cerebrospinal fluid (CSF) on the brain, resulting in increased pressure on the skull and widening of cavities (ventricles) of the brain. CSF is the watery protective fluid that circulates through the four 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 on 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), feeding difficulties, vomiting, irritability, headache, loss of coordination and/or reduction in mental functioning. In severe cases, potentially life-threatening complications may result. In those with Dandy-Walker malformation, cystic malformation of the fourth ventricle of the brain may lead to hydrocephalus with increased prominence of the back region of the head (occiput), and/or additional associated anomalies. A small number of affected individuals have agenesis of the corpus callosum, or partial or complete absence (agenesis) of an area of the brain that connects the two cerebral hemispheres. Agenesis of the corpus callosum can range in severity and may result in seizures and/or developmental delays.
In some instances, additional physical features have been reported in association with mosaic trisomy 9 including clouding of the cornea of the eye, presence of cysts on one or both eyeballs (epibulbar dermoids), underdevelopment of the lungs (pulmonary hypoplasia), diaphragmatic hernia and/or gastroesophageal reflux. In individuals with a diaphragmatic hernia, there is protrusion of abdominal structures into the chest cavity through an abnormal opening in the diaphragm often in addition to gastroesophageal reflux, which is characterized by backflow (reflux) of stomach acid into the esophagus. This condition can cause inflammation of and possible damage to the esophageal lining. A gastroenterologist is often necessary to monitor and treat these digestive conditions.
In individuals with mosaic trisomy 9, the entire 9th chromosome appears three times (trisomy) rather than twice in some cells of the body (mosaicism). Chromosomes are found in the nucleus, or central part, 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.
The same chromosomal makeup is usually present in all body cells. However, those with mosaicism have two or more cell lines that are chromosomally distinct. In individuals with mosaic trisomy 9, there is trisomy (three copies) of chromosome 9 in a percentage of cells, while other cells have a typical chromosomal makeup with two copies. The additional chromosome causes the symptoms and physical findings (phenotype) that are seen in the disorder. Individuals with a low percentage of affected cells (low mosaicism) may have fewer, less severe symptoms than those with a high percentage of affected cells (high mosaicism). The percentage of mosaicism can fluctuate depending on where the sample is drawn (cheek swab versus blood for example) and the age of the individual.
Mosaic trisomy 9 appears to result from errors of chromosomal separation (nondisjunction) during meiosis, which is the division of reproductive cells (sperm or eggs) in the parents. It has also been shown to occur during cellular division after fertilization (mitosis). There have been some reports in which the disorder has appeared to occur due to a balanced chromosomal rearrangement (pericentric inversion) in one of the parents. A pericentric inversion is characterized by breakage of a chromosome in two places including the centromere and reunion of the segment in the reverse order. If a chromosomal rearrangement is balanced, meaning that the genetic material is in a different order but is in the correct quantity, it is usually harmless to the carrier. However, such a chromosomal rearrangement may result in a child with unbalanced genetic material.
Chromosome studies and genetic counseling are typically recommended for parents with a child diagnosed with mosaic trisomy 9. These can help confirm or exclude the presence of a pericentric inversion or other chromosomal rearrangement involving chromosome 9 in one of the parents. In addition, knowing the chromosome structure of the parents can inform them of the risk for future children.
Mosaic trisomy 9 appears to affect males and females of all ethnicities in relatively equal numbers. Some research has found more females with this diagnosis. Since the disorder was originally described in 1973 (Haslam RH), over 100 cases have been reported in the medical literature.
Mosaic trisomy 9 may be suspected based on characteristic physical findings. The diagnosis can be confirmed with chromosomal analysis. It may be necessary to use multiple testing methods and to collect samples from various tissue sites to detect low-level mosaicism.
Diagnostic evaluation may require various studies, including advanced imaging techniques to help detect and/or characterize certain anomalies that may be associated with the disorder (e.g., craniofacial differences, skeletal anomalies, brain anomalies). A thorough cardiac evaluation may be advised to detect any heart defects that may be present. Such evaluation may include a thorough clinical examination, evaluation of heart and lung sounds with a stethoscope, x-ray studies, tests that record the electrical activities of the heart muscle (electrocardiography [EKG]); a technique in which sound waves are directed toward the heart, enabling evaluations of cardiac motion and structure (echocardiogram); or other measures based on concerns (e.g., feeding difficulties may require bronchoscopy).
The treatment of mosaic trisomy 9 is directed toward the specific symptoms in each individual. Such treatment requires the coordinated efforts of a team of medical professionals such as pediatricians; surgeons; heart specialists (cardiologists); physicians who diagnose and treat problems of the skeleton, joints, muscles, and related tissues (orthopedists); neurologists and/or other health care professionals.
In affected individuals with congenital heart defects, treatment with specific medications, surgical intervention, and/or other measures may be required. For those with hydrocephalus, disease management may include administration of specific medications to help reduce the rate of cerebrospinal fluid (CSF) production, shunting, or other measures. (Shunts are specialized devices that drain excess CSF away from the brain to another part of the body for absorption into the bloodstream). In addition, in some cases, physicians may recommend surgical repair or correction of other craniofacial, musculoskeletal, genital and/or other complications associated with the disorder. The specific surgical procedures performed will depend upon the nature and severity of the anatomical differences, their associated symptoms, and other factors.
Early intervention services are important in assisting affected children reach their potential. These services are provided to infants and toddlers. Services continue when the child reaches the age of three. Special services include special education services, physical therapy, occupational therapy, speech therapy, feeding therapy and/or other services to meet individual needs such as vision therapy. Upon reaching adulthood, medical, social/recreational and vocational or employment related services are often necessary.
Genetic counseling is recommended for families of affected children.
The Tracking Rare Incidence Syndromes (TRIS) project is designed to raise awareness and provide support for families and professionals involved in the care of children and adults with rare trisomy conditions. The TRIS project seeks to increase the knowledge base on rare incidence trisomy conditions, and to make this information available to families and interested educational, medical and therapeutic professionals. For more information, contact:
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: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
For more information about clinical trials conducted in Europe, contact:
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., intellectual disability, craniofacial differences, congenital heart defects, etc.].)
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