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 13, Partial Monosomy 13q is a rare chromosomal disorder in which a portion of the long arm (q) of chromosome 13 is missing (deleted or monosomic). The range and severity of symptoms may vary greatly, depending upon the exact size and location of the deletion on 13q. Chromosome 13, Partial Monosomy 13q is usually apparent at birth and may be characterized by low birth weight, malformations of the head and facial (craniofacial) area, abnormalities of the eyes, defects of the hands and/or feet, genital malformations in affected males, and/or additional physical abnormalities. Affected infants and children may also exhibit delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation) as well as varying degrees of mental retardation. In the majority of cases, Chromosome 13, Partial Monosomy 13q appears to occur randomly, for no apparent reason (sporadic).
In Chromosome 13, Partial Monosomy 13q, a rare chromosomal disorder, a portion of the long arm (q) of chromosome 13 is missing (deleted). Symptoms and physical characteristics associated with the disorder may vary greatly, depending upon the exact size and location of the deletion (monosomy) on chromosome 13q.
In many cases, infants with Chromosome 13, Partial Monosomy 13q have a low birth weight and may fail to grow at the expected rate (failure to thrive). Moderate to severe growth delays may continue during childhood, resulting in short stature. In addition, in most cases, affected individuals exhibit a severe delay in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation). Severe mental retardation is also present in most cases. However, in some affected individuals, the degree of mental retardation may be mild or moderate.
Many infants with Chromosome 13, Partial Monosomy 13q may exhibit characteristic abnormalities of the head and facial (craniofacial) area such as an unusually small head (microcephaly); a wide, flat nasal bridge; a small lower jaw (micrognathia) with an abnormally prominent upper jaw (maxilla); protruding front teeth (incisors), large, low-set ears; and/or a short neck with abnormal skin folds (webbing). In some cases, in addition to exhibiting microcephaly, some affected infants may experience premature closure (craniosynostosis) of the fibrous joints (metopic sutures) between the two sides of the bone in the forehead (frontal bone). As a result, the head may have an unusual “triangular-shaped” appearance with a prominent forehead (trigonocephaly). Affected children with trigonocephaly may be at risk for abnormal development of the forebrain (holoprosencephaly). (For more information on this condition, choose “Holoprosencephaly” as your search term in the Rare Disease Database.)
In rare, severe cases, additional craniofacial abnormalities may include incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove in the upper lip (cleft lip). (For more information on these conditions, choose “Cleft Palate and Cleft Lip” as your search terms in the Rare Disease Database.)
Many infants and children with Chromosome 13, Partial Monosomy 13q also exhibit various eye (ocular) abnormalities. These often include unusually small eyes (microphthalmia), widely spaced eyes (ocular hypertelorism), drooping of the upper eyelids (ptosis), and/or vertical skin folds on either side of the nose (epicanthal folds) that may partially cover the eyes’ inner corners. Affected individuals may also exhibit abnormal clouding of the lens of the eye (cataract) and/or the front (anterior), clear portion of the eye through which light passes (corneal opacity). In addition, some tissue from the colored portion of the eye (iris) may be absent (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other eye tissues (i.e., the choroid). Such eye abnormalities may result in varying degrees of visual impairment or, in some cases, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.
In some cases, infants and children with Partial Monosomy 13q may also exhibit a malignant tumor of the retina (retinoblastoma), the nerve-rich membrane lining the eyes. In such cases, both eyes are usually affected (bilateral retinoblastoma). Symptoms associated with retinoblastoma may include the appearance of a whitish mass in the pupil area behind the lens of the eye (leukokoria or “cat’s eye reflex”), crossed eyes (strabismus), diminished vision or blindness, pain and redness, and/or an abnormal buildup of pressure of the fluid of the eye (secondary glaucoma).
Some individuals with Chromosome 13, Partial Monosomy 13q may also have malformations of the hands and/or feet. These may include underdeveloped (hypoplastic) or absent thumbs; fifth fingers that are abnormally bent (clinodactyly), webbing or fusion of certain fingers (syndactyly), unusually short big toes; and/or feet that are twisted in an abnormal position (talipes equinovarus or clubfoot). In some cases, affected individuals may exhibit additional skeletal abnormalities. These may include malformations of the ribs, abnormalities of bones in the spinal column (vertebrae), and/or sideways curvature of the spine (scoliosis).
In some cases, males with Chromosome 13, Partial Monosomy 13q may have genital abnormalities. For example, the urinary opening (meatus) may appear on the underside of the penis (hypospadias), and/or the testes may fail to descend into the scrotum (cryptorchidism). In some cases, the scrotum may be unusually small and/or abnormally divided into two sections (bifid scrotum); the penis may be unusually small (micropenis), and/or an abnormal passage may be present between the scrotum and the anus (perineal fistula). In rare cases, the anal opening may be absent or covered by a thin membrane, causing obstruction (anal atresia).
In some severe cases, individuals with Chromosome 13, Partial Monosomy 13q may also exhibit abnormalities of certain internal organs including the heart, brain, intestines, and/or kidneys.
In some cases, heart malformations may be associated with Partial Monosomy 13q including Atrial and Ventricular Septal Defects, which are rare heart defects that are present at birth (congenital). The normal heart has four chambers with two upper chambers known as atria. They are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers of the heart are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. A small opening between the two atria (foramen ovale) is present at birth. Shortly after birth, the atrial septum gradually closes and covers this opening. In infants with Atrial Septal Defects, the atrial septum may not close properly or may be malformed during fetal development. As a result, the opening between the atria persists long after it should be closed, causing an increase in the workload on the right side of the heart and excessive blood flow to the lungs.
Most children with Atrial Septal Defects exhibit no symptoms. However, in some cases, associated symptoms may include abnormal thinness, mild growth delays, and an increased susceptibility to repeated respiratory infections. In rare cases, severely affected children may experience breathlessness, easy fatigability with exercise, and/or irregular heartbeats (arrhythmias).
Ventricular Septal Defects are characterized by an abnormal opening in the fibrous partition separating the two ventricles (ventricular septum). The size and location of the defect determine the severity of the symptoms. Small Ventricular Septal Defects may close on their own (spontaneously) or become less significant as the child matures and grows. Moderately-sized defects may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive cardiac failure). Symptoms associated with cardiac failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), abnormal enlargement of the liver (hepatomegaly), and/or failure to thrive. Large Ventricular Septal Defects can cause life-threatening complications during infancy. Persistent elevation of the pressure within the artery that carries blood away from the heart and to the lungs (pulmonary artery) can cause permanent damage to the lungs.
As mentioned above, affected infants with trigonocephaly may be at risk for abnormal development of the forebrain (holoprosencephaly). In some cases of Chromosome 13, Partial Monosomy 13q, additional brain abnormalities may be present such as absence (agenesis) of certain portions of the brain (e.g., rhinencephalon and/or corpus callosum), protrusion of membranes that surround the brain (meninges) through an abnormal opening in the skull (meningocele), and/or an abnormal accumulation of cerebrospinal fluid in the skull, causing increased pressure on the brain (hydrocephaly).
In addition, some individuals with Partial Monosomy 13q may also have Hirschsprung’s Disease, a disorder in which absence of nerve fibers (ganglia) in the muscle wall of the colon prevents the muscles from working to push waste materials (feces) through the lower digestive tract (peristalsis) . As a result, feces accumulate abnormally in the involved portion of the colon, causing massive widening (dilatation) of the colon (megacolon), diarrhea, constipation, abdominal distention, nausea, periodic vomiting, and/or loss of appetite (anorexia). (For more information on this disorder, choose “Hirschsprung” as your search term in the Rare Disease Database.)
In rare cases, some individuals with Partial Monosomy 13q may also exhibit kidney (renal) abnormalities. These may include underdevelopment (hypoplasia) or absence (agenesis) of a kidney.
Chromosome 13, Partial Monosomy 13q is a rare chromosomal abnormality in which a portion of the long arm (q) of chromosome 13 is missing (deleted). 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” and a long arm identified by the letter “q”. Chromosomes are further subdivided into bands that are numbered. For example, “13q32” refers to band 32 on the long arm of chromosome 13.
In cases of Partial Monosomy 13q, the deletion of a portion of chromosome 13q is responsible for the symptoms and findings that characterize this chromosomal disorder. The range and severity of associated abnormalities may depend upon the exact length and location of the deleted portion of chromosome 13q.
Researchers have attempted to determine the specific symptoms and physical characteristics (phenotype) that may be associated with deletion of certain band locations on chromosome 13q. The medical literature suggests that proximal deletions that do not extend into band q32 appear to be associated with growth retardation, mild to moderate mental retardation, and varying physical abnormalities. (“Proximal” indicates nearest the point of attachment, nearest the center, or proximity to the point of origin.) Those with involvement of band q14 have a risk for retinoblastoma (see below). In addition, evidence suggests that deletions involving a portion of band q32 may be associated with growth retardation, severe mental retardation, abnormalities of the hands and feet, brain malformations, eye abnormalities, and other major malformations. Individuals with deletions limited to the end portion of 13q beyond band q32 (i.e., distal deletions involving bands q33-q34) may have severe mental retardation and, in some cases, craniofacial abnormalities. Many researchers have suggested that such distal deletions do not usually appear to be associated with major malformations. However, according to one report, a distal deletion was present in a male child with myelomeningocele, an abnormally small head (microcephaly), minor facial abnormalities, and other findings. Myelomeningocele is a developmental defect in which a sac containing a portion of the spinal cord, its protective membranes (meninges), and cerebrospinal fluid abnormally protrudes through a defect in the spinal (vertebral) column. Research is ongoing concerning specific band regions that may be critical in producing certain features potentially associated with 13q deletions.
As mentioned above, for those individuals with retinoblastoma, researchers have determined that the chromosomal region consistently missing is a portion of band q14 (13q14). Based upon this finding, it is suspected that a gene or genes at this chromosomal location may play a role in fetal retinal development. However, it is important to note that not all individuals with a 13q14 deletion develop retinoblastoma. According to the medical literature, approximately 20 percent of those with a deletion involving band 13q14 have the malignancy.
The exact cause of Chromosome 13, Partial Monosomy 13q is not fully understood. In most documented cases, Partial Monosomy 13q appears to be due to spontaneous (de novo) errors very early in embryonic development. In such cases, the parents of the affected child usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality. However, in other cases, Chromosome 13, Partial Monosomy 13q may be due to a parental chromosomal rearrangement. In some cases, the parental chromosomal rearrangement may be a “balanced translocation.” Translocations occur when regions of certain chromosomes break off and are rearranged, resulting in shifting of genetic material and an altered set of chromosomes. A translocation is balanced if it consists of an altered but balanced set of chromosomes.
In other cases, the parental chromosomal rearrangement may be an inversion or an insertion. An inversion occurs when a chromosome breaks in two places and the segment then rejoins the chromosome in the reverse order. An insertion occurs when a segment of one chromosome is inserted into a break that exists in another chromosome in a different chromosomal (nonhomologous) pair.
If such chromosomal rearrangements are balanced, they are usually harmless to the carrier. However, they are sometimes associated with a higher 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 a chromosomal rearrangement in one of the parents.
Chromosome 13, Partial Monosomy 13q appears to affect females slightly more frequently than males. Although rare, deletions involving chromosome 13q are among the most commonly observed monosomies. Since the disorder was originally reported in 1963, more than 125 cases have been recorded in the medical literature.
In some cases, the diagnosis of Chromosome 13, Partial Monosomy 13q may be determined before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During chorionic villus sampling, a tissue sample is removed from a portion of the placenta. Chromosomal studies performed on this fluid or tissue sample may indicate a partial monosomy of chromosome 13q.
The diagnosis of Chromosome 13, Partial Monosomy 13q may confirmed after birth (postnatally) based upon a thorough clinical evaluation, characteristic physical findings, chromosomal studies, and, in some cases, specialized enzyme testing (assay). According to the medical literature, if affected individuals exhibit mental retardation, growth delays, and/or retinoblastoma in association with craniofacial and/or digital abnormalities, a diagnosis of Chromosomal 13, Partial Monosomy 13q should be considered.
In some cases, affected individuals with retinoblastoma may exhibit reduced activity of a certain enzyme (esterase D) due to deletions involving band q14 on chromosome 13. Researchers have determined that the genes for retinoblastoma and esterase D are very close together (proximal) on chromosome band 13q14 (i.e., the retinoblastoma gene maps to 13q14.1-q14.2, while the esterase D gene maps to 13q14.11). Therefore, both genes may be deleted in some individuals with Partial Monosomy 13q. As a result, an enzyme study (assay) that measures the levels of esterase D may be conducted as a screening test in individuals diagnosed with Chromosome 13, Partial Monosomy 13q to help predict the possible development of retinoblastoma. If such an assay reveals abnormally low levels of the esterase D enzyme, an affected individual should be carefully, regularly monitored for the possible development of the tumor.
Retinoblastoma may be detected based upon characteristic clinical findings and specialized imaging tests. The most common presenting signs indicating retinoblastoma include the appearance of a whitish mass in the pupil area behind the lens of the eye (leukokoria or "cat's eye reflex") and abnormal deviation of the eye (strabismus). Specialized imaging tests used to confirm retinoblastoma and/or characterize the tumor may include regular X-ray studies, the use of a special instrument to examine the interior of the eye (ophthalmoscopy), computer-assisted tomography (CT), magnetic resonance imagin. (MRI), and/or ultrasonography. During MRI, a magnetic field and radio waves are used to create cross-sectional images of the eye. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of the eye's tissue structure. In ultrasonography, reflected sound waves are used to create images. Additional specialized tests may also be conducted to further characterize the nature of the malignancy and to help determine potential, appropriate treatments.
The diagnosis of certain congenital heart defects (e.g., Atrial or Ventricular Septal Defects) occurring in association with Chromosome 13, Partial Monosomy 13q may be confirmed by a thorough clinical examination and specialized tests that allow physicians to evaluate the structure and function of the heart. These tests may include X-ray studies, electrocardiogram (EKG), echocardiogram, and cardiac catheterization. X-ray studies may reveal abnormal enlargement of the heart (cardiomegaly) or malformation of other heart structures. An EKG, which records the heart's electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, ultrasonic waves are directed toward the heart, enabling physicians to study cardiac function and motion. During cardiac catheterization, a small hollow tube (catheter) is inserted into a large vein and threaded through the blood vessels leading to the heart. This procedure allows physicians to determine the rate of blood flow through the heart, measure the pressure within the heart, and/or thoroughly identify anatomical abnormalities.
Hirschsprung's Disease may be diagnosed by barium enema, a procedure in which a special contrast medium is infused into the rectum and X-rays are then taken of the area. Microscopic examination of a small tissue sample removed from the mucous membranes that line the rectum (biopsy) may confirm absence of nerve fibers (ganglia).
Specialized imaging studies and/or additional tests may also be used to reveal other eye (ocular) abnormalities; certain genital, skeletal, kidney (renal), and/or brain malformations; and/or additional physical abnormalities potentially associated with Chromosome 13, Partial Monosomy 13q.
The treatment of Chromosome 13, Partial Monosomy 13q is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, eye specialists, physicians who treat malignancies (oncologists), radiologists, cardiologists, neurologists, physicians who specialize in diagnosing and treating skeletal abnormalities (orthopedists), and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
In some cases, treatment may include surgical repair of certain malformations. For example, surgery may be performed to correct certain craniofacial, ocular, genital, skeletal, cardiac, and/or other malformations that may be associated with this disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities and their associated symptoms.
In affected children with retinoblastoma, the treatments used may depend upon whether one or both eyes are affected and/or the possibility of preserving and/or restoring vision. If one eye is affected (unilateral retinoblastoma), the eye may be surgically removed (enucleation) along with a portion of the optic nerve. Radiation and/or chemotherapy may then be conducted. If the tumor is very small, radiation alone may be used in some cases. If both eyes are involved (bilateral retinoblastoma), the more affected eye may be surgically removed while the other eye may be treated with antibiotics, radiation, chemotherapy, a procedure that uses extreme cold to destroy tissue (cryotherapy), and/or a procedure that uses intense, focused light (e.g., laser therapy) to heat and destroy tissue (photocoagulation). Corrective lenses and/or other measures may be used to help improve vision after treatment for retinoblastoma.
In some cases, children with Partial Monosomy 13q may have visual problems resulting from additional eye abnormalities (e.g., colobomas, microphthalmia, cataracts). Corrective glasses, contact lenses, surgery, and/or other measures may also be used in such cases to help improve visual abnormalities.
In affected children with craniosynostosis and trigonocephaly, surgery may be performed to correct the premature closure of the bones in the skull. In those with hydrocephalus, shunts may be implanted to drain excess cerebrospinal fluid away from the brain, relieving pressure.
In many cases, Atrial or Ventricular Septal Defects may be corrected surgically. Before surgery, medical management may include treatment of symptoms related to congestive heart failure. Drugs such as digoxin may help to prevent irregular heartbeats and excessively rapid heartbeats (tachycardia). Restriction of salt in the diet, drugs that help to eliminate excessive fluid from the body (diuretics), and/or bed rest may also be effective therapies for congestive heart failure. In some cases, surgery may not be indicated for infants with small Ventricular Septal Defects that may close on their own or become less significant as the child matures and grows. Conservative treatment may include careful monitoring of symptoms and heart function.
In addition, nutritional considerations may be important in infants with Atrial or Ventricular Septal Defects. Respiratory infections should be treated vigorously and early. Because of the risk of bacterial infection of the lining of the heart (endocarditis) and the heart valves, individuals with Atrial or Ventricular Septal Defects may be given antibiotic drugs before any surgical procedure, including dental procedures such as tooth extractions.
In individuals with Partial Monosomy 13q who also exhibit Hirschsprung's Disease, the condition may often be corrected surgically during early childhood.
Other treatment of Chromosome 13, Partial Monosomy 13q is symptomatic and supportive. A team approach may be helpful in ensuring that affected individuals reach their fullest potential. Such a team approach may include special remedial education, physical therapy, and other medical, social, or vocational services. Genetic counseling will be of benefit for families of children with Chromosome 13, Partial Monosomy 13q. Chromosomal studies are necessary to determine whether a chromosomal rearrangement is present in one of the parents.
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., mental retardation, craniofacial abnormalities, retinoblastoma, congenital heart defects, Hirschsprung's disease.].)
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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 180200; 7/24/00. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?180200.
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