NORD gratefully acknowledges 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 9, Partial Monosomy 9p is a rare chromosomal disorder in which there is deletion (monosomy) of a portion of the 9th chromosome. Characteristic symptoms and findings include mental retardation; distinctive malformations of the skull and facial (craniofacial) region, such as an abnormally shaped forehead (i.e., trigonocephaly), upwardly slanting eyelid folds (palpebral fissures), and unusually flat midfacial regions (midfacial hypoplasia); structural malformations of the heart (congenital heart defects); genital defects in affected males and females; and/or additional physical abnormalities. In most cases, Chromosome 9, Partial Monosomy 9p appears to result from spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically).
Most infants with Chromosome 9, Partial Monosomy 9p have a normal birth weight and length. However, the disorder is typically characterized by variable delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation) and moderate or mild mental retardation. Reports indicate that affected individuals tend to have an affectionate, friendly, and sociable personality.
As noted above, Chromosome 9, Partial Monosomy 9p is also associated with characteristic abnormalities of the skull and facial (craniofacial) region. In many affected infants, there is premature fusion of the fibrous joint (i.e., metopic suture) between bones forming the forehead (craniosynostosis), resulting in an abnormally narrow, pointed, “triangular-” or “keel-shaped” forehead (trigonocephaly). In addition, the back of the head (occiput) may appear unusually flat. Additional characteristic craniofacial malformations may include widely spaced eyes (ocular hypertelorism); upwardly slanting eyelid folds (palpebral fissures); vertical skin folds that may cover the eyes’ inner corners (epicanthal folds); and/or highly arched eyebrows. In addition, the eyes may appear unusually prominent. Many affected infants also have unusually flat midfacial regions (midfacial hypoplasia), including a short nose, flattened nasal bridge, and upturned nostrils (anteverted nares); an abnormally long vertical groove in the center of the upper lip (philtrum); and/or a small jaw (micrognathia) and small mouth with protruding lips. Additional craniofacial abnormalities may also be present, such as a highly arched roof of the mouth (palate); low-set, malformed ears; and/or a short, broad, somewhat webbed neck with a low hairline.
Individuals with Chromosome 9, Partial Monosomy 9p may also have various malformations of the hands and feet. Such abnormalities may include unusually long fingers or toes (digits) due to increased length of the middle bones (phalanges) of the digits; abnormal skin ridge patterns of the fingertips; a single crease across the palms of the hands; and/or abnormally short, square (i.e., hyperconvex) fingernails and toenails.
According to reports in the medical literature, approximately one- to two-thirds of affected infants may also have structural malformations of the heart at birth (congenital heart defects). Such cardiac defects may include an abnormal opening in the partition (septum) that separates the two lower chambers (ventricles) of the heart (ventricular septal defects); abnormal narrowing (stenosis) of the opening between the pulmonary artery and the right ventricle (pulmonary stenosis); and/or patent ductus arteriosus (PDA). In individuals with PDA, the channel that is present between the pulmonary artery and the aorta during fetal development fails to close after birth. (The pulmonary artery carries oxygen-depleted blood from the right ventricle to the lungs, where the exchange of oxygen and carbon dioxide occurs. The aorta, the major artery of the body, arises from the left ventricle and supplies oxygen-rich blood to most arteries.) In those with cardiac defects, associated symptoms and findings may vary, depending upon the size, nature, and combination of heart malformations present and other factors. Some individuals may show no apparent symptoms (asymptomatic), while others may develop 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 individuals with the disorder, Chromosome 9, Partial Monosomy 9p may also be characterized by genital defects. In affected males, such abnormalities may include a small penis (micropenis); undescended testes (cryptorchidism); and/or abnormal placement of the urinary opening (hypospadias), such as on the underside of the penis. In females, the two long folds of skin on either side of the vaginal opening (labia majora) may be underdeveloped (hypoplastic), while the two small folds of skin between the labia majora and the vaginal opening (labia minora) may be larger than normal (hyperplastic).
In addition, in some affected infants, there may be protrusion (herniation) of a portion of the intestine into the canal that passes through lower muscular layers of the abdominal wall (inguinal hernia). (In males, the inguinal canal is the tubular passageway through which the testes normally descend from the abdomen into the scrotum before birth.) Some with the disorder may also have an umbilical hernia or an omphalocele. An umbilical hernia is a skin-covered protrusion of intestine and the fold of fatty membrane in front of the intestine (omentum) through a defect in the abdominal wall at the navel (i.e., the umbilicus, where the umbilical cord joined the fetal abdomen). An omphalocele is a herniation of varying amounts of abdominal contents (e.g., intestines and, in severe cases, other abdominal organs) around the umbilicus, with the bulging area covered by a membrane-like sac consisting of peritoneum without overlying skin. (The peritoneum is the membrane lining the abdominal wall and covering internal abdominal organs.) In infants with an omphalocele, potentially life-threatening complications may result due to rupture of the sac, damage to tissues due to drying, and/or infection.
Additional physical abnormalities have also been reported in association with Partial Monosomy 9p. Such abnormalities have included sudden episodes of uncontrolled electrical activity in the brain (seizures), widely spaced nipples, abnormal curvature of the spine, and/or, more rarely, incomplete closure (clefting) of the palate (cleft palate), bony or membranous blockage of the passageway between one or both sides of the nose and the throat (choanal atresia), and/or other features.
In individuals with Chromosome 9, Partial Monosomy 9p, there is deletion (monosomy) of part of the end (distal) region of the short arm (p) of chromosome 9. (“Distal” indicates away or farthest from a particular point of reference, meaning the chromosome’s centromere [described below].) 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, “9p22” refers to band 22 of the short arm of chromosome 9.
The range and severity of associated symptoms may depend on the specific length and location of the monosomic portion of 9p. Evidence suggests that most individuals with characteristic features of this chromosomal syndrome have deletions beginning within band 9p22 (breakpoint) that may extend to the end (or “terminal”) of chromosome 9p. (The distal region of 9p is sometimes referred to as “9p2” and includes bands 9p21 through 9p24, the latter of which is the terminal band of 9p.)
In most cases, Chromosome 9, Partial Monosomy 9p appears to be caused by spontaneous (de novo) errors very early in embryonic development that occur for unknown reasons (sporadically). In such instances, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.
In other instances, Partial Monosomy 9p may result from a “balanced translocation” in one of the parents. 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.
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, Partial Monosomy 9p has appeared to affect females more frequently than males. Since the disorder was originally described, more than 100 cases have been reported in the medical literature.
In some instances, Chromosome 9, Partial Monosomy 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 the presence of Partial Monosomy 9p.
In most cases, the disorder is diagnosed or confirmed after birth (postnatally) based upon a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. Various specialized tests may also be performed to help detect and/or characterize certain abnormalities that may be associated with the disorder. For example, a thorough cardiac evaluation may be advised to detect any heart abnormalities that may be present. Such evaluations may include a thorough clinical examination, evaluation of heart and lung sounds through use of a stethoscope, and specialized tests that enable physicians to evaluate the structure and function of the heart (e.g., x-ray studies, electrocardiography [EKG]), echocardiography).
The treatment of Chromosome 9, Partial Monosomy 9p is directed towards the specific symptoms that are apparent in each individual. Such disease management may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; heart specialists (cardiologists); physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); 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, for infants with an omphalocele, the abnormality is typically surgically repaired soon after birth. In some cases, physicians may also recommend surgical repair or correction of certain craniofacial malformations (e.g., craniosynostosis), genital defects, hernias, 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.
As noted above, rare cases have also been reported in which infants are affected by blockage of the passageway between the nose and throat (choanal atresia). Because choanal atresia may result in associated breathing, feeding, and swallowing problems, initial treatment for such infants may also require prompt establishment of an oral airway or creation of an opening through the neck into the windpipe into which a tube is inserted (tracheostomy). In addition, supportive measures to help improve feeding may include use of modified artificial nipples or tube feeding (gavage feeding). Surgical correction of choanal atresia may be recommended during the newborn (neonatal) period or later during childhood, based upon the severity of the condition, the presence of other medical problems, and/or other factors.
For individuals affected by seizures, treatment may include the administration of anticonvulsant medications to help prevent, reduce, or control seizure episodes.
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 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
Email: [email protected]
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., mental retardation, congenital heart defects, craniofacial abnormalities, etc.].)
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