Chromosome 3, Trisomy 3q2 is a rare chromosomal disorder in which a portion of the 3rd chromosome appears three times (trisomy) rather than twice in cells of the body. Associated symptoms and findings may be variable, depending upon the specific length and location of the duplicated (trisomic) portion of chromosome 3. However, many affected infants and children have developmental delays, mental retardation, and characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. Such craniofacial abnormalities may include a relatively short head (brachycephaly), widely spaced eyes (ocular hypertelorism), upwardly slanting eyelid folds (palpebral fissures), and a small nose with upturned nostrils (anteverted nares). Affected infants and children also tend to have long eyelashes; arched, bushy, well-defined eyebrows that grow together across the base of the nose (synophrys), an unusually low hairline on the forehead and the back of the neck; and generalized excessive hair growth (hirsutism). Chromosome 3, Trisomy 3q2 may also be characterized by eye (ocular) abnormalities, limb defects, structural heart malformations (congenital heart defects), or other physical features.
The symptoms and physical findings associated with Chromosome 3, Trisomy 3q2 may be variable. However, in many cases, the disorder is characterized by mental retardation, moderate to severe developmental delays, abnormally diminished muscle tone (hypotonia), distinctive abnormalities of the head and facial (craniofacial) area, and/or additional physical abnormalities. According to reports in the medical literature, craniofacial features and other physical abnormalities associated with Trisomy 3q2 are often very similar to those associated with a rare genetic disorder known as Cornelia de Lange syndrome. (For further information on Cornelia de Lange syndrome, please see the “Related Disorders” section of this report below.)
Many infants with Trisomy 3q2 have characteristic craniofacial abnormalities. Such features may include a relatively short, wide head (brachycephaly); widely spaced eyes (ocular hypertelorism); upwardly slanting eyelid folds (palpebral fissures), and vertical skin folds covering the eyes’ inner corners (epicanthal folds). Affected infants may also have a relatively small nose with upturned nostrils (anteverted nares), a thin upper lip, downwardly turning corners of the mouth, a small, receding lower jaw (microretrognathia), and an abnormally prominent vertical groove (philtrum) between the nose and the upper lip. In addition, there may be incomplete closure (clefting) or abnormally high arching of the roof of the mouth (palate). Affected infants and children may also have a low hairline on the forehead and the back of the neck, an abnormally short neck with excessive skin folds, unusually long eyelashes; arched, bushy, well-defined eyebrows that grow together across the base of the nose (synophrys), and generalized excessive hair growth (hirsutism).
Many infants with Chromosome 3, Trisomy 3q2 may also have eye (ocular) abnormalities, such as increased fluid pressure within the eyes (glaucoma); loss of transparency of the lenses (cataracts), clouding of the front, usually transparent regions of the eyes (corneal opacities), or rapid, involuntary eye movements (nystagmus). Additional ocular abnormalities may include deviation of one eye in relation to the other (strabismus), absence or defects of ocular tissue (colobomata) involving the colored regions of the eyes (irides); or abnormal smallness of the eyes (microphthalmia). Due to such features, affected individuals may have varying degrees of visual impairment.
Trisomy 3q2 may also be characterized by abnormalities of the fingers or toes. For example, there may be underdevelopment (hypoplasia) of certain bones within the ends of the fingers (distal phalanges), causing the hands to appear unusually short. Affected individuals may also have inward deviation or bending (clinodactyly) of certain fingers or toes (digits), permanent flexion of one or more digits (camptodactyly), or webbing or fusion (syndactyly) of certain toes.
Some infants and children with Trisomy 3q2 may also have additional physical abnormalities. Genital defects may sometimes be present, such as undescended testes (cryptorchidism) in affected males and malformations of the internal genitals in females with the disorder. In some cases, additional abnormalities may include structural malformations of the heart at birth (congenital heart defects), kidney (renal) defects, or underdevelopment of certain regions of the brain.
In individuals with Chromosome 3, Trisomy 3q2, all or a portion of the end (distal) region of the long arm (q) of chromosome 3 is present three times (trisomy) rather than twice in cells of the body. (This distal region is sometimes referred to as “chromosome 3q2.”) 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, “3q26” refers to band 26 within the distal region of the long arm of chromosome 3.
Trisomy (or duplication) of a certain region or regions of chromosome 3q2 is responsible for the symptoms and findings that characterize the disorder. The severity and range of symptoms may depend on the specific length and location of the duplicated portion of the chromosome. In addition, evidence suggests that individuals with features characteristic of the disorder typically have duplications involving bands 26.3-27.3 on chromosome 3q, indicating that this may be a critical region in producing the syndrome.
In some affected individuals (75%), Chromosome 3, Trisomy 3q2 may be due to the presence of a “balanced” rearrangement in one of the parents. The rearrangement is often a translocation, but inversions may also be involved. Translocations occur when regions of different chromosomes break off and are interchanged, resulting in shifting of genetic material and an altered set of chromosomes. For example, a translocation is balanced if pieces or bands of two chromosomes break off and switch places, resulting in an altered but balanced set of chromosomes in which all the chromosomal material is present in two copies. Balanced translocations are usually harmless to the carrier. However, such a chromosomal rearrangement may cause an “unbalanced translocation” in the carrier’s offspring. An unbalanced translocation occurs when only one of the two chromosomes involved in the translocation is inherited from a carrier parent. The result is too much (duplication or trisomy) or too little (deletion or monosomy) chromosomal material. Chromosomal testing may determine whether a parent has a balanced translocation.
In some affected individuals, duplication of chromosome 3q2 has appeared to occur spontaneously for unknown reasons (de novo) during early embryonic development. The parents of a child with a “de novo” duplication usually have normal chromosomes and a relatively low risk of having another child with the chromosomal abnormality.
In a few individuals with Trisomy 3q2, the disorder has resulted from a chromosomal inversion in one of the parents. Chromosomal inversions are characterized by breakage within a single chromosome at two points and “rejoining” of the chromosome with an inversion or a reversal of the affected chromosomal segment between the two breakpoints. Chromosomal testing may also determine whether a parent has a chromosomal inversion.
Chromosome 3, Trisomy 3q2 appears to affect males and females in equal numbers. At least 50 cases have been reported in the medical literature. In some cases, the disorder may be suspected before birth (prenatally) based upon the results of specialized tests. (For further information, please see the “Standard Therapies” section of this report below.) The disorder is usually detected or confirmed at birth or during early infancy based upon characteristic symptoms and physical findings.
In some cases, a diagnosis of Chromosome 3, Trisomy 3q2 may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, or chorionic villus sampling (CVS). During fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus. 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 analyzed. CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on cells from the fluid or tissue samples may reveal the presence of Trisomy 3q2.
The diagnosis of Chromosome 3, Trisomy 3q2 is typically made at birth or during infancy based upon a thorough clinical evaluation, detection of characteristic physical findings, and chromosomal analysis. In some affected individuals, specialized testing may also be conducted to detect and/or characterize certain abnormalities that may be associated with the disorder (e.g., ocular abnormalities, congenital heart defects, renal malformations, etc.).
The treatment of Chromosome 3, Trisomy 3q2 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 who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; surgeons, specialists who diagnose and treat abnormalities of the skeleton, joints, muscles, and related tissues (orthopedists), physicians who specialize in heart abnormalities (cardiologists), eye specialists (ophthalmologists), and/or other health care professionals.
In some affected individuals, treatment may include surgical repair of certain craniofacial, digital, ocular, cardiac, or other abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors. Other treatment is symptomatic and supportive.
Early intervention may be important in ensuring that children with Chromosome 3, Trisomy 3q2 reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Chromosome 3, Trisomy 3q2 and their families.
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