Angelman Syndrome

Classification according to ICD-10
Q93.5	Other deletions of a part of a chromosome - Angelman syndrome
ICD-10 online (WHO version 2019)

The Angelman syndrome is the result of a rare genetic variation on chromosome 15 ( microdeletion on the maternal chromosome or uniparental disomy 15q11-13). It is often associated with developmental delays, cognitive disabilities , above-average happiness and a greatly reduced development of spoken language .

The British pediatrician Harry Angelman (1915–1996) first described the syndrome, which was later named after him, from a scientific point of view in 1965 . He called it because of the eye-catching movement pattern and the frequent laughter of the children he looked after then, Happy Puppet Syndrome ( Engl. Happy , happy 'and puppet , doll').

The life expectancy of people with Angelman syndrome is not reduced.

5 year old girl with Angelman Syndrome

frequency

Both boys and girls can be affected by Angelman syndrome. In 1965, Angelman described 150 case studies; In 2005 there were over 800 known worldwide. The syndrome has an average frequency of 1 in 15,000 to 1 in 20,000.

Common symptoms

A wide variety of features have been documented over time that are common in people with Angelman syndrome. Not all affected persons have all characteristics and the existing characteristics do not appear equally in all of them:

• Frequent, often objectively unfounded smiles and laughter ( unmotivated laughter ), sometimes real fits of laughter, often when excited and stressed
• cognitive disability
• often hyperactivity
• Difficulty concentrating , often short attention spans, but often good memory for faces and directions, good spatial orientation
• in early childhood often no attempts to speak, no babbling , later only very limited verbal articulation ability (expressive language), but a certain ability to learn alternative forms of communication , e.g. B. the signs according to the system of the sign-supported communication (GuK), image communication
• good receptive language (language comprehension)
• Longer than average duration of the oral phase (exploring the environment with the mouth )
• Movement and balance disorders, ataxia (usually stiff, awkward, swaying, wide-legged gait, jerky, jerky (running) movements, one in ten children does not learn to walk)
• Delay in motor development (as a result, for example, comparatively late learning to walk)
• Perception disorders in the physical area (often for example balance problems )
• large mouth with protruding upper jaw
• comparatively small teeth, which are often quite far apart
• often excessive mouth and chewing movements due to insufficient control of the mouth muscles
• excessive salivation
• Insomnia from a lack of one or more of the hormones that control healthy sleep
• comparatively small head ( microcephaly ), which is often flattened at the back
• Unusual sticking out of the tongue (in around 50% of people)
• Epilepsy usually begins between the 3rd and 36th month after birth , the seizures often disappear again in adolescence, around the age of 16 (occurrence in up to 90% of those affected)
• Special features in the EEG , also independent of epilepsy and also detectable during sleep
• Stunted growth
• often curvature of the spine ( scoliosis ) during puberty
• small hands and feet, feet turned outwards
• Often very weakly pigmented skin , light hair and blue eyes ( hypopigmentation , sometimes parallels to albinism )
• Squint ( strabismus ) with a frequency of 50%
• excessive sweating, particular sensitivity to heat

Other specifications

People with Angelman syndrome often get noticed through an intensive search for physical contact. They usually have a good sense of humor , are often very social, usually friendly in their attitude and they laugh a lot, even if they often have no objective reason and are often excited.

Hyperactivity is a noticeable feature of the syndrome, and particularly in childhood (but often beyond), extreme sleep disorders are sometimes common. These are caused by a hormone deficiency and cannot be regulated educationally. Many children with Angelman syndrome require nighttime restraint , e.g. B. by means of a shoulder-stomach belt, so that they come to rest.

Despite the inability to learn to speak properly (on average six words can be articulated in a loud and understandable manner), people with Angelman Syndrome are usually able to use simple, sometimes very subjective gestures , e.g. B. to learn according to the principle of sign-supported communication (GuK), to use pictures for communication or to use gestures for understanding.

People with Angelman Syndrome remain dependent on the help of others for life. They can be developed intellectually to varying degrees, but mostly to a very limited extent, and they usually require special help and, above all, permanent personal support in learning and in coping with everyday life.

Many people with Angelman syndrome have a particular preference for water . You like to go swimming, like to play with water and are fascinated by reflections on water or z. B. also on glass surfaces . Plastic, in particular material that cracks strongly, such as plastic bags or packaging, also holds a strong fascination for most people.

Often times, people with Angelman syndrome enjoy looking at pictures of themselves and close caregivers.

genetics

Angelman syndrome is caused by lack of expression of UBE3A - gene in the brain caused. The chromosome segment 15q11-q13 on chromosome 15 on which this gene is located is subject to so-called imprinting . This means that certain genes in this section are only active on the father-derived chromosome and others only on the mother-derived chromosome. In Angelman's syndrome, the maternal chromosome segment is not functional and the UBE3A gene on the paternal chromosome is imprinted; thus the gene product is completely absent . If it is not the maternal but the paternal chromosome segment that is defective, this leads to Prader-Willi syndrome .

In 50 to 80 out of 100 people with Angelman syndrome, the cause of the peculiarity lies in a deletion (= loss of pieces) of maternal chromosome 15 in the area 15q11-q13 (partly with translocation ).

Two to five out of 100 people have a uniparental disomy (UPD) 15. In the case of Angelman syndrome, the child inherited both chromosomes 15 from the paternal parent (paternal disomy) and none from the mother.

Eight to eleven out of 100 people with Angelman syndrome have a gene mutation in the UBE3A gene on the maternal chromosome.

An error in imprinting can be detected in around five out of 100 people. This may be due to a mutation caused by epigenetics or due to a mutation or deletion of the imprinting center. This is a stretch of DNA that controls the differential epigenetic modification (such as DNA methylation ) of seven genes on the paternal and maternal chromosomes. This leads to activation or inactivation of the gene. Imprinting means that the UBE3A gene is active and expressed on the maternal chromosome , but UBE3A is inactivated on the paternal chromosome. If the function of the imprinting center is disturbed, this results in a missing or faulty methylation pattern, which, among other things, can lead to Angelman syndrome.

Angelman syndrome can have an inherited component. The parents are not affected, but have certain chromosome features that increase the likelihood of fathering a child with Angelman syndrome. This can be seen in the striking frequency of affected siblings . A mutation in the UBE3A gene, for example, can be passed on silently through the male side of a family over generations . If the grandfather carries a mutation that he passes on to his daughter, this is not noticeable in the daughter either, since the mutation is on the paternal chromosome. The daughter then has a 50% risk of having a child with Angelman syndrome.

diagnosis

The diagnosis is made on average between the ages of three and seven by child neurologists (based on abnormal EEG values, regardless of epilepsy, even during sleep) or by geneticists (based on a cytogenetic or molecular genetic examination):

It is possible to diagnose Angelman's syndrome in some of the affected children by means of a genetic test, but not in all of the children whose clinical symptoms are believed to be the presence of the syndrome. A positive genetic test can determine Angelman syndrome with certainty, but a negative test does not rule it out.

In many cases, the parents of the child turn to their pediatrician with suspected Angelman syndrome , as they have informed themselves in advance of certain typical abnormalities in order to find an explanation for the peculiarities of their child. Observing the child's behavior and appearance can be of great help in the diagnosis.

Differential diagnostics

Differential diagnostics include ATR-X syndrome , Christianson syndrome or Mowat-Wilson syndrome and microdeletion syndrome 2q23.1 .

therapy

There is no causal cure for Angelman syndrome. Appropriate treatment of the multiple epilepsy , squint ( strabismus ) and curvature of the spine ( scoliosis ) is medically relevant .

Otherwise, the most common support methods that have a positive effect on the development of children with Angelman syndrome are remedial early intervention , mototherapy , physiotherapy , occupational therapy , speech therapy , sensory integration therapy and therapeutic riding . The special preference for water can also be used therapeutically.

Quotes

• Every child is unique and different, and so are these special children. (Marga Hogenboom, 2003, p. 108.)
• These children are very open and open-minded. They like to make eye contact, look at everyone with their blue eyes, so that you feel as if you are plunging into unimagined depths, as you encounter no resistance, no sign of antipathy in their gaze. (Marga Hogenboom, 2003, p. 104.)

Individual evidence

1. ↑ K. Buiting: Prader-Willi Syndrome and Angelman Syndrome . In: Am. J. Med. Genet. Part C Semin. Med. Genet . 154C, no. 3 , August 2010, p. 365-376 , PMID 20803659 .

literature

• Marga Hogenboom: Understanding people with intellectual disabilities better. Congenital syndromes clearly explained. 2nd Edition. Reinhardt, Munich 2006, ISBN 3-497-01850-3 .
• Klaus Sarimski: Developmental Psychology of Genetic Syndromes. 3. Edition. Hogrefe, Göttingen 2003, ISBN 3-8017-1764-X .
• Claudia Färber: Analysis of gene sequences in the Prader-Willi, Angelmann syndrome region . Utz, Munich 2000, ISBN 3-89675-723-7 .

See also

• List of syndromes

Web links

• Angelman eV self-help association
• Angelman Syndrome Foundation (English)
• Fishing man Melanie della Rossa

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !