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Angelman Syndrome

Angelman syndrome (AS) is a neurological disorder characterized by severe congenital mental retardation, unusual facial appearance, and muscular abnormalities.

The genetic basis of AS is very complex, but the majority of cases are due to a deletion of segment 15q11-q13 on the maternally derived chromosome 15. When this same region is missing from the paternally derived chromosome, an entirely different disorder, Prader-Willi syndrome, results. This phenomenon, when the expression of genetic material depends on whether it has been inherited from the mother or the father, is termed genomic imprinting.

Symptoms:

A. Consistent (100%)

  • Developmental delay, functionally severe
  • Speech and language impairment, lack of speech or minimal use of words
  • Receptive and nonverbal communication skills higher than verbal ones
  • Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
  • Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span

B. Frequent (more than 80%)

  • Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
  • Seizures, onset usually before 3 years of age
  • Abnormal EEG, characteristic pattern with large amplitude slow-spike waves (usually 2-3/s), facilitated by eye closure

C. Associated (20-80%)

  • Flat occiput (back of the head)
  • Occipital groove
  • Protruding tongue
  • Tongue thrusting; suck/swallowing disorders
  • Feeding problems during infancy
  • Prognathia (projecting jaw)
  • Wide mouth, wide-spaced teeth
  • Frequent drooling
  • Excessive chewing/mouthing behaviors
  • Strabismus
  • Hypopigmented skin, light hair and eye color (compared to family), seen only in deletion cases
  • Hyperactive lower limb deep tendon reflexes
  • Uplifted, flexed arm position especially during ambulation
  • Increased sensitivity to heat
  • Sleep disturbance
  • Attraction to/fascination with water

Today, we know that Angelman Syndrome is a genetic disorder caused by abnormal function of the gene UBE3A, located within a small region (q11-q13) on chromosome 15. This region is deleted from the maternally-derived chromosome in approximately 70% of individuals with Angelman Syndrome. Other chromosome 15 changes that lead to lack of a functional maternal copy of UBE3A (such as UBE3A mutations, imprinting defects, or paternal uniparental disomy) are found in 15-20% of individuals with Angelman Syndrome. The remaining 10-15% of individuals with Angelman Syndrome, however, have normal genetic laboratory studies; for these individuals, the diagnosis is based solely upon clinical findings.

Angelman Syndrome occurs in approximately 1/15,000 live births and affects males, females and all racial/ethnic groups equally.

Join the Contact Registry for this Disorder | Find a Clinical Trial | Back to Top | Angelman Syndrome Foundation


Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is a congenital (present from birth) condition characterized by obesity (if the weight is not carefully controlled), low muscle tone, cognitive disabilities, and incomplete pubertal development.

PWS is the result of the loss of several genes on the chromosome 15, inherited from the father. This loss is typically due to a small chromosomal deletion that arose spontaneously in one of the father's germ cells. If the same chromosomal region is deleted in the chromosome 15 inherited from the mother, this results in a much different syndrome called Angelman syndrome. This phenomenon, where there is a difference in the expression of the genes inherited from the father and the mother, is called "genomic imprinting". Most of our genes are not subject to "imprinting", but a defect in the imprinting process is known to be involved in several birth defects, such as PWS.

Signs of PWS are typically seen at birth. This includes low muscle tone and poor feeding. Most PWS babies need assistance with feeding including feeding tubes. Male infants frequently have undescended testicles. Typically the PWS infant is slower to achieve developmental milestones including sitting, walking and talking. At around 18-36 months of age if not appropriately controlled, the child with PWS starts gaining weight rapidly and can become morbidly obese. Compounding the weight problem is the development of a constant sense of hunger which can begin anywhere from 3 to 12 years of age.

Affected children have an intense craving for food, thus external controls and a strict food regime are essential to avoid a weight gain that could eventually be life-threatening. Access to food must be closely monitored to avoid morbid obesity (the degree of obesity that seriously affects health) which could lead to respiratory failure with hypoxia (low blood oxygen levels), cor pulmonale (right-sided heart failure), and death. Fortunately, due to early intervention and education of parents, there is now a large generation of children and young adults with PWS who are slim. Almost all individuals with PWS have some degree of learning difficulties, even if they have a normal IQ, and will need special help in school. In addition, many individuals with PWS may develop behavioral problems which can be responsive to behavioral management and medications. There is also delayed and incomplete development of secondary sexual characteristics including puberty. Almost all individuals with PWS are infertile, but there have been a few rare cases of females becoming pregnant.

Frequently the diagnosis of PWS is not made until the child is several years of age. However, with the increased awareness of PWS and the good genetic tests now available many physicians are making the diagnosis of PWS early in infancy. Making a diagnosis at an early age allows physicians to begin management sooner thus minimizing many of the problems with PWS. Support and education of parents and other family members is crucial. Generally there are a number of health care professionals involved in the care of the child with PWS. This typically includes a geneticist, endocrinologist, nutritionist and behavioral therapist, as well as the primary care physician. It may also include a psychiatrist, orthopedist and neurologist.

Join the Contact Registry for this Disorder | Find a Clinical Trial | Back to Top | Prader-Willi Syndrome Association


Rett Syndrome

Rett syndrome is a childhood neurodevelopmental disorder characterized by apparently normal early development followed by loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, gait abnormalities, seizures, and mental retardation. It affects females almost exclusively.

The course of Rett syndrome, including the age of onset and the severity of symptoms, varies from child to child. Before the symptoms begin, however, the child appears to grow and develop normally. Then, gradually, mental and physical symptoms appear. Hypotonia (loss of muscle tone) is usually the first symptom. As the syndrome progresses, the child loses purposeful use of her hands and the ability to speak. Other early symptoms may include problems crawling or walking and diminished eye contact. The loss of functional use of the hands is followed by compulsive hand movements such as wringing and washing. The onset of this period of regression is sometimes sudden.

Another symptom, apraxia - the inability to perform motor functions - is perhaps the most severely disabling feature of Rett syndrome, interfering with every body movement, including eye gaze and speech.

Individuals with Rett syndrome often exhibit autistic-like behaviors in the early stages. Other symptoms may include toe walking; sleep problems; wide-based gait; teeth grinding and difficulty chewing; slowed growth; seizures; cognitive disabilities; and breathing difficulties while awake such as hyperventilation, apnea (breath holding), and air swallowing.

Join the Contact Registry for this Disorder | Find a Clinical Trial | Back to Top | International Rett Syndrome Association

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