Chromosome 15, Distal Trisomy 15q

rarediseases.org/rare-diseases/chromosome-15-distal-trisomy-15q/

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.

Synonyms of Chromosome 15, Distal Trisomy 15q

Chromosome 15, Trisomy 15q2

Distal Duplication 15q
Partial Duplication 15q Syndrome

General Discussion

Chromosome 15, Distal Trisomy 15q is an extremely rare chromosomal disorder in which
the end (distal) portion of the long arm (q) of the 15th chromosome (15q) appears three
times (trisomy) rather than twice in cells of the body. The disorder is characterized by
growth delays before and/or after birth (prenatal and/or postnatal growth retardation);
mental retardation; and/or distinctive malformations of the head and facial
(craniofacial) area. Additional abnormalities typically include an unusually short neck;
malformations of the fingers and/or toes; abnormal sideways curvature of the spine
(scoliosis) and/or other skeletal malformations; genital abnormalities, particularly in
affected males; and/or, in some cases, heart (cardiac) defects. The range and severity of
symptoms and physical findings may vary from case to case, depending upon the length
and location of the duplicated portion of chromosome 15q. In most cases, Chromosome
15, Distal Trisomy 15q is due to a chromosomal balanced translocation in one of the
parents.

Signs & Symptoms

In individuals with Chromosome 15, Distal Trisomy 15q, an extremely rare chromosomal
disorder, the end (distal) portion of the long arm (q) of chromosome 15 (15q) is
duplicated (trisomic). Symptoms and physical characteristics associated with the
disorder may vary in range and severity, depending upon the exact size and location of
the duplicated portion of chromosome 15q.

In some cases, Chromosome 15, Distal Trisomy 15q may be characterized by abnormally
slow growth before and/or after birth (prenatal and/or postnatal growth retardation) . In
addition, many affected infants experience swallowing and feeding difficulties that may
be due to the presence of certain malformations of the head and facial (craniofacial)

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area. Such feeding and swallowing difficulties may result in or contribute to an affected
infant’s failure to grow or gain weight at the expected rate (failure to thrive). However, in
certain rare cases (i.e., trisomy 15q25-qter), affected individuals may exhibit abnormally
tall stature. (For more information on trisomy 15q25-qter, see the “Causes” section
below.)

Most infants with Chromosome 15, Distal Trisomy 15q also exhibit abnormally
diminished muscle tone (hypotonia). In addition, most affected infants and children
have severe to profound mental retardation. However, in rare cases (i.e., trisomy 15q25-
qter), only mild mental retardation may be present.

Many infants and children with the disorder have characteristic malformations of the
head and facial (craniofacial) area. In some cases, the fibrous joints between certain
bones in the skull (sagittal sutures) close prematurely (craniosynostosis), causing the
head to appear abnormally long and narrow (dolichocephaly). In addition, in many
cases, the head may appear abnormally small (microcephaly), with abnormal bulging
(prominence) of the back of the head (occiput) and a sloping forehead. In addition, the
face may appear dissimilar from one side to the other (facial asymmetry). In rare cases
(i.e., trisomy 15q25-qter), affected infants may have hydrocephalus, a condition
characterized by inhibition of the normal flow of cerebrospinal fluid (CSF) within and
abnormal widening (dilatation) of the cerebral spaces of the brain (ventricles), causing
accumulation of CSF in the skull and potentially increased pressure on brain tissue.

Additional craniofacial malformations typically associated with the disorder may include
downwardly slanting, short, and/or narrow eyelid folds (palpebral fissures); drooping of
the upper eyelids (ptosis); an abnormally large, prominent, and/or rounded (bulbous)
nose with a broad nasal bridge; and/or an unusually small, triangular mouth. In
addition, many affected infants and children may have an abnormally long groove in the
upper lip (philtrum), a crease in the center (midline) of the lower lip, a highly arched
roof of the mouth (palate), an unusually small jaw (micrognathia), and/or abnormally
round, “puffy” cheeks. In some cases, the ears may be abnormally large, low-set, and/or
malformed (dysplastic). In addition, the neck may be short and/or webbed, which, in
some cases, may be due to malformations of certain bones in the upper portion of the
spine (cervical vertebrae). Approximately one third of affected infants and children may
also experience episodes of uncontrolled electrical disturbances in the brain (seizures).

In addition, most infants and children with Chromosome 15, Distal Trisomy 15q have
skeletal abnormalities affecting the fingers, toes, chest (thorax), and/or spine. Affected
individuals may have unusually long, thin fingers and/or toes (arachnodactyly),
permanently flexed fingers (camptodactyly), and/or excessive extension
(hyperextension) of the thumbs. In addition, the joints of the hands and feet may
become fixed in a permanently flexed position (joint contractures). Affected individuals
may also have side-to-side curvature of the spine (scoliosis) and/or abnormal depression
of the sternum, the bone forming the center of the chest (“funnel chest” or pectus
excavatum).

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In many cases, individuals with Chromosome 15, Distal Trisomy 15q also have genital
abnormalities. In males, such abnormalities may include failure of the testes to descend
into the scrotum (cryptorchidism) and/or low levels of testicular function
(hypogonadism), resulting in delayed development of secondary sexual characteristics
(i.e., deepening of the voice, characteristic hair growth patterns, sudden increase in
growth and development of the testes and scrotum, etc.). Some affected females may
exhibit underdevelopment of the two long folds of skin on either side of the vaginal
opening (labia majora).

In addition, many affected infants may have abnormalities of the heart (congenital heart
defects) and/or may exhibit an increased susceptibility to recurrent respiratory tract
infections. In some cases, swallowing and feeding difficulties may cause food to be
inhaled (aspirated) into the lungs, which may result in severe lung infections (aspiration
pneumonia). In some cases, such abnormalities may result in life-threatening
complications.

Causes

Chromosome 15, Distal Trisomy 15q is an extremely rare chromosomal disorder in which
the end (distal) portion of the long arm (q) of the 15th chromosome appears three times
(trisomy) rather than twice in cells of the body. Chromosomes are found in the nucleus
of all body cells except red blood 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, “15q21” refers to band 21 on the long arm of chromosome 15.

The duplication of the distal portion of chromosome 15q is responsible for the symptoms
and physical features that characterize this disorder. The range and severity of associated
abnormalities may depend upon the exact length and location of the duplicated portion
of chromosome 15q.

According to investigators, in those with Chromosome 15, Distal Trisomy 15q, the
duplicated portion of 15q usually begins between bands 15q21 and 15q23 (breakpoint)
and extends toward the end or “terminal” portion of chromosome 15q (qter). In rare
cases, the breakpoint has occurred at band 15q25. According to the medical literature,
although individuals with trisomy 15q25-qter have many of the characteristic
abnormalities typically associated with the disorder, there may be some differences. (For
further information, please see the “Symptoms” section above.) A few families have also
been described in which the breakpoint has occurred at band 15q15.

In most cases, Chromosome 15, Distal Trisomy 15q is due to a chromosomal “balanced
translocation” in one of the parents. 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. If a chromosomal rearrangement is balanced, meaning

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that it consists of an altered but balanced amount of genetic material, it is usually
harmless to the carrier. However, such a chromosomal rearrangement may be associated
with an increased risk of unbalanced chromosome inheritance 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.

According to the medical literature, in the case of parental balanced translocations that
result in Distal Trisomy 15q, the second chromosome involved with chromosome 15q has
varied from case to case; however, symptoms and findings characteristically associated
with the disorder (clinical phenotype) appear consistent.

Affected Populations

Chromosome 15, Distal Trisomy 15q is an extremely rare chromosomal disorder that is
thought to affect males approximately twice as often as females. Since the disorder was
originally described in the medical literature in 1974 (A. Fujimoto), more than 30 cases
have been reported in the literature. The majority of symptoms and physical features
associated with the disorder are apparent at birth.

Related Disorders

Other chromosomal disorders may be characterized by prenatal and postnatal growth

retardation, mental retardation, distinctive craniofacial abnormalities, genital
malformations, congenital heart defects, and/or other abnormalities similar to those
potentially associated with Chromosome 15, Distal Trisomy 15q. Chromosomal testing is
necessary to confirm the specific chromosomal abnormality present. (For further
information on such disorders, choose the name of the specific chromosomal disorder in
question or use “chromosome” as your search term in the Rare Disease Database.)

Diagnosis

In some cases, the diagnosis of Chromosome 15, Distal Trisomy 15q 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
reveal the presence of Distal Trisomy 15q.

Chromosome 15, Distal Trisomy 15q may also be diagnosed and/or confirmed after birth
(postnatally) based upon a thorough clinical evaluation, identification of characteristic
physical findings, and chromosomal studies.

Certain specific abnormalities that may occur in association with Distal Trisomy 15q may
be detected and/or confirmed by specialized imaging studies and/or additional tests. For
example, specialized x-ray studies may be used to confirm and/or characterize certain

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skeletal abnormalities potentially associated with the disorder (e.g., dolichocephaly,
micrognathia, cervical vertebral abnormalities, scoliosis). Congenital heart defects
potentially associated with Chromosome 15, Distal Trisomy 15q may be detected,
confirmed, and/or characterized by a thorough clinical evaluation and specialized tests
that allow physicians to evaluate the structure and function of the heart (e.g., x-ray
studies, electrocardiogram [EKG] echocardiogram, cardiac catherization). In addition, in
some cases, electroencephalography (EEG), which records the brain's electrical
impulses, may reveal brain wave patterns that are characteristic of certain types of
seizure activity.

Standard Therapies

Treatment

The treatment of Chromosome 15, Distal Trisomy 15q 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, physicians who specialize in
diagnosing and treating disorders of the skeletal system (orthopedists), and/or other
health care professionals may need to systematically and comprehensively plan an
affected child's treatment.

The treatment of Chromosome 15, Distal Trisomy 15q may include surgical repair of
certain malformations. In some cases, surgery may be performed to correct congenital
heart defects, craniofacial malformations, webbing of the neck, flexion contractures,
abnormalities of the hands and/or feet, genital malformations, and/or other
abnormalities that may be associated with the disorder. The surgical procedures
performed will depend upon the severity and location of the anatomical abnormalities
and their associated symptoms.

In some cases, abnormalities involving the joints, tendons, muscles, and bones (e.g.,
flexion contractures, malformations of the fingers and/or toes, scoliosis) may be treated
with orthopedic techniques potentially in combination with surgery. Physical therapy
may also be prescribed to help improve coordination of movements (mobility).

In addition, physicians may recommend preventive measures for affected infants and
children who may be prone to repeated respiratory infections. Physicians may also
regularly monitor affected individuals for such infections to ensure early detection and
appropriate, prompt treatment.

Early intervention is important to ensure that children with Chromosome 15, Distal
Trisomy 15q reach their potential. Special services that may be beneficial to affected
children may include special remedial education, special social support, and/or other
medical, social, and/or vocational services.

Genetic counseling will be of benefit for families of children with Chromosome 15, Distal
Trisomy 15q. Chromosomal studies are necessary to determine whether a balanced
translocation is present in one of the parents. Other treatment for the disorder is
symptomatic and supportive.

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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:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: [email protected]

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

www.centerwatch.com

Resources

(Please note that some of these organizations may provide information concerning
certain conditions potentially associated with this disorder [e.g., craniofacial
malformations, congenital heart defects, seizures, mental retardation, etc.].)

NORD Member Organizations

Children’s Craniofacial Association

13140 Coit Road
Suite 517
Dallas, TX 75240 USA
Phone: (214) 570-9099
Toll-free: (800) 535-3643
Email: [email protected]
Website: http://www.ccakids.com
Chromosome Disorder Outreach, Inc.
P.O. Box 724
Boca Raton, FL 33429-0724 USA
Phone: (561) 395-4252
Email: [email protected]
Website: http://www.chromodisorder.org/

Other Organizations

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 American Heart Association
7272 Greenville Avenue
Dallas, TX 75231
Phone: (214) 784-7212
Toll-free: (800) 242-8721
Email: [email protected]
Website: http://www.heart.org
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Phone: (301) 251-4925
Toll-free: (888) 205-2311
Website: http://rarediseases.info.nih.gov/GARD/
NIH/National Institute of Neurological Disorders and Stroke
P.O. Box 5801
Bethesda, MD 20824
Phone: (301) 496-5751
Toll-free: (800) 352-9424
Website: http://www.ninds.nih.gov/
Support Organization for Trisomy 18, 13, and Related Disorders
2982 S. Union Street
Rochester, NY 14624-1926
Toll-free: (800) 716-7638
Email: [email protected]
Website: http://www.trisomy.org
The Arc
1825 K Street NW, Suite 1200
Washington, DC 20006
Phone: (202) 534-3700
Toll-free: (800) 433-5255
Email: [email protected]
Website: http://www.thearc.org
UNIQUE – Rare Chromosome Disorder Support Group
G1 The Stables
Station Road West
Oxted, RH8 9EE United Kingdom
Phone: 004401883723356
Email: [email protected]
Website: http://www.rarechromo.org/html/home.asp

References

TEXTBOOKS

Jones KL. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia,
PA: W.B. Saunders Company; 1997:62-63.

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Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications,
Inc.; 1990:374-75.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford
University Press; 1990:90.

JOURNAL ARTICLES

Cora T, et al. A partial trisomy 15q due to 15;17 translocation detected by conventional
cytogenetic and FISH techniques. Genet Couns. 2000;11:25-32.

Zollino M, et al. Partial duplication of the long arm of chromosome 15: confirmation of a
causative role in craniosynostosis and definition of a 15q25-qter trisomy syndrome. Am J
Med Genet. 1999;87:391-94.

Fryns JP, et al. The fetal phenotype in 15q2 duplication. Ann Genet. 1988;31:123-25.

Nazarenko SA, et al. Trisomy of the distal 15q region due to familial balanced
translocation t(15;16) (q24;p13) and unusual mosaicism in the mother of the proband.
Tsitol Genet. 1987;21:434-37.

Lacro RV, et al. Duplication of distal 15q: report of five new cases from two different
translocation kindreds. Am J Med Genet. 1987;26:719-28.

Garcia-Cruz D, et al. Trisomy 15q23—-qter due to a de novo t(11;15) (q25;q23) and

assignment of the critical segment. Ann Genet. 1985;28:193-96.

Orye E, et al. Mosaic and non-mosaic trisomy 15q2. Ann Genet. 1985;28:58-60.

Schnatterly P, et al. Distal 15q trisomy: phenotypic comparison of nine cases in an

extended family. Am J Hum Genet. 1984;36:444-51.

Tzancheva M, et al. Two familial cases with trisomy 15q dist due to a rcp (5;15) (p14;q21).
Hum Genet. 1981;56:275-77.

Gregoire MJ, et al. Duplication 15q22 to 15qter and its phenotypic expression. Hum
Genet. 1981;59:429-33.

Castel Y, et al. Partial trisomy 15q due to maternal translocation t (7;15) (q35;14). Ann
Genet. 1976;19:15-19.

Fujimoto A, et al. Inherited partial duplication of chromosome no. 15. J Med Genet.
1974;11:287-91.

Years Published

1997, 2001, 2003, 2009

The information in NORD’s Rare Disease Database is for educational purposes only and is not
intended to replace the advice of a physician or other qualified medical professional.

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