Information on the following diseases can be found in the Related Disorders section of this report:

• Mental Retardation (General)

The major characteristics of Angelman Syndrome include an abnormally small head (microcephaly) and a flattened groove on the back of the head (occipital), sometimes with an indented horizontal groove. Children with this disorder may have a protruding jaw (mandible), an abnormally large mouth (macrostomia), widely spaced teeth, and/or a frequently visible, thrusting tongue. Affected children smile often and easily and may have episodes of excessive laughter. This may not occur because of happiness, but as the result of a brain stem defect.

Children with Angelman Syndrome usually present with varying degrees of developmental delay. Standard IQ testing usually reveals severe to profound mental retardation. However, some children with this disorder seem to understand some verbal communication (receptive language), although speech is usually absent (mutism). Children with Angelman Syndrome usually have severe motor problems (slow motor development), decreased muscle tone, jerky limb movements, and hand flapping. Patients usually have an impaired ability to coordinate movement (ataxia) and poor balance. Seizures commonly develop in the early years of life. However, episodes of seizures may decrease with age. (For more information on seizures, choose "Epilepsy" as your search term in the Rare Disease Database.)

Other characteristics of Angelman Syndrome may include poor feeding habits (especially in infants), irregular patterns of sleep, and hyperactivity.
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Angelman Syndrome usually appears to occur spontaneously (sporadically) for unknown reasons. However, some familial cases of the disorder have also been reported. Research suggests that sporadic and familial Angelman Syndrome result from disruption or deletion of a gene or genes on the long arm (q) of chromosome 15 (15q11-q13). This chromosomal region is sometimes referred to as the "Angelman Syndrome chromosome region" (ANCR).

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.

In most individuals with Angelman Syndrome, genetic material is deleted from chromosome 15q11-q13. According to reports in the medical literature, the deleted chromosome always appears to be derived from the mother (maternally derived). (When the deletion affects the paternally derived chromosome, a different disorder, known as Prader-Willi Syndrome, may result. For further information on this disorder, please choose "Prader Willi" as your search term in the Rare Disease Database.)

In addition, in some rare cases, affected individuals may have inherited two copies of chromosome 15q from the father yet no copies from the mother (paternal isodisomy). (Human traits are normally the product of the interaction of two genes, one received from the father and one from the mother.) In other words, evidence suggests that Angelman Syndrome may result from lost expression of certain maternal genes from the 15q11-q13 chromosomal region, due to deletion or paternal isodisomy.

In still other cases, investigators indicate that Angelman Syndrome may be caused by new, sporadic changes (mutations) of a gene known as UBE3A (or the E-6 associated protein ubiquitin-protein ligase gene). In addition, researchers suggest that some cases of the disorder may result from sporadic mutations of other currently unidentified genes (i.e., resulting in "imprinting" defects).

Research is ongoing to learn more about the complex genetic mechanisms that may be responsible for Angelman Syndrome. (For further information, please see the "Investigational Therapies" section of this report below.)

Angelman Syndrome is an extremely rare disorder that affects males and females in equal numbers. Over 700 cases have been reported in the United States. It is believed that many cases of Angelman Syndrome may not be diagnosed.

Symptoms of the following disorders can be similar to those of Angelman Syndrome. Comparisons may be useful for a differential diagnosis:

There are many types of mental retardation with numerous causes. Angelman Syndrome can be distinguished from other forms of mental retardation because of the distinctive facial appearance, unusual smiling and laughter, unusual jerky "puppet-like" walk, and abnormal electrical brain wave patterns. (For more information on mental retardation, choose "Retardation" as your search term in the Rare Disease Database.)

The treatment of Angelman Syndrome may require advice and services from several specialists. These may include neurologists, orthopedists, physical therapists, nutritionists, social workers, educators, ophthalmologists, psychologists or psychiatrists, and/or dentists. Family support services may be beneficial in learning how to cope with this disorder.

Genetic counseling may be helpful for the families of patients with Angelman Syndrome. Other treatment is symptomatic and supportive. A nurturing environment, including the interaction of parents and other caregivers, may help children with Angelman Syndrome to develop to their fullest potential.

Blood samples are needed for genetic research on Angelman Syndrome. The French pharmaceutical company Genethon is conducting the studies. Interested individuals should contact:

Association Francaise Contre Les Myopathies
1, rue de I'Internationale
91002 EVRY
CEDEX (FRANCE)

Research on genetic disorder and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.


NORD does not promote, endorse, nor encourage participation in any specific medical research study. This information is presented to further scientific understanding that could lead to the prevention, treatment, and/or cure of rare disorders. NORD recommends that anyone interested in participating in a clinical research program seek the advice or counsel of his or her own personal physician(s).

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 105830; Last Update: 11/5/01.

TEXTBOOKS
Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA; W.B. Saunders Company; 1997:200-201.

Buyse ML. Birth Defects Encyclopedia. Dover, MA; Blackwell Scientific Publications, Inc.; 1990:140-141.

REVIEW ARTICLES
Singh R, Gardner RJ, Crossland KM, et al. Chromosomal abnormalities and epilepsy: a review for clinicians and gene hunters. Epilepsia. 2001;43:127-40.

Philippart M. Rett and Angelman’s syndromes: models of arrested development. Pediatr Neurol. 2001;25:288-94.

Nicholls RD, Knepper JL. Genome organization, function and imprinting in Prader-Willi and Angelman syndromes. Annu Rev Genomics Hum Genet. 2001;2:153-75.

Williams CA, Lossie A, Driscoll D. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet. 2001;101:59-64.

Cassidy SB, Dykens E, Williams CA. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet. 2000;97:136-46.

Rougeulle C, Lalance M. Angelman syndrome: how many genes to remain silent. Neurogenetics. 1998;1:229-37.

JOURNAL ARTICLES
Duker PC, van Driel S, van de Bercken J. Communications profiles of individuals with Down’s syndrome, Angelman syndrome and pervasive developmental disorder. J intellect Diabil Res. 2002;46(Pt 1):35-40.

Tharapel AT, Kadandale JS, Martens PR, et al. Prader Willi/Angelman and DiGeorge/velocardiofacial syndrome deletions: diagnosis by primed in situ labeling (PRINS). Am J Med Genet. 2002;107:119-22.

Lossie AC, Whitney MM, Amidon D, et al. Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet. 2001;38:834-45.

Davies W, Isles AR, Wilkinson LS. Imprinted genes and mental dysfunction. Ann Med. 2001;33:428-36.