Angelman syndrome

Angelman syndrome is the result of a rare Genbesonderheit on chromosome 15 ( microdeletion on the maternal chromosome or uniparental disomy 15q11 -13), which is accompanied, among others with mental and motor developmental delays, cognitive disabilities, hyperactivity, and a greatly reduced spoken language.

History

The British pediatrician Harry Angelman (1915-1996) with the Department of Neurology described in 1965, which was later named after him syndrome for the first time from a scientific viewpoint. He called it due to the eye-catching movement pattern and the frequent laughter of children, which he then looked after Happy Puppet Syndrome ( engl. happy, happy ' and puppet, doll ').

Frequency of occurrence

Both boys and girls can be born with Angelman syndrome. In 1965 Angelman described 150 case studies; in 2005 were more than 800 documented. The special case occurs with an average frequency of 1: 20,000, which is to be assumed that Angelman syndrome is often not diagnosed as such, but for example as autism: 15000-1.

Common Symptoms

With a variety of characteristics of the time has been recorded, which are common in people with Angelman Syndrome. Not all people have all the features that existing features do not occur in the same strong expression:

  • Frequent, often objectively unfounded smile and laugh ( unmotivated laughter), some outright laughter, often with excitement and stress
  • Cognitive disability
  • Often hyperactivity
  • Difficulty concentrating, frequent, short attention span, but often good memory for faces and directions, good spatial orientation
  • In infancy often not speaking tests, no babbling, later only very limited phonetic articulation skills ( expressive language ), but some ability to learn alternative forms of communication, such as gestures after the sign - supported communication system ( GuK ), image communication
  • Good receptive language ( comprehension )
  • Longer than average duration of oral phase (exploration of the environment with the mouth )
  • Movement and balance disorders, ataxia ( usually rather stiff, awkward, fluctuating, breitbeiniger transition, jerky, chopped ( run ) movements, one in ten children do not learn to walk )
  • Delay in motor development ( thereby also eg comparatively late learning to walk )
  • Perceptual disturbances in the physical realm (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 due to insufficient control of the mouth muscles
  • Excessive salivation
  • Sleep by a deficiency of at least one of the hormones that control the sound sleep
  • Relatively small head ( microcephaly ), which is often flattened at the rear
  • Unusual emphasis stretching the tongue ( at about 50 % of those affected )
  • Epilepsy with onset usually between the 3rd and 36th month after birth, the seizures often disappear in adolescence, at about the age of 16, again (occurring in up to 90 % of those affected )
  • Special features in the EEG, independently of epilepsy and also detectable in sleep
  • Growth disorders
  • Often curved spine (scoliosis ) in adolescence
  • Small hands and feet, out-turned feet
  • Often very weakly pigmented skin, light hair and blue eyes ( hypopigmentation, some parallels with albinism )
  • Squint (strabismus ) with a frequency of occurrence of 50 %
  • Excessive sweating, special heat sensitivity

Other features

People with Angelman syndrome often fall through a thorough search after body contact. They usually have a great sense of humor, are often very social, usually in the basic attitude of friendly and they laugh a lot, though often objectively baseless and often with excitement.

Hyperactivity is a prominent feature of the syndrome, particularly in childhood ( but often beyond) are often partly extreme insomnia. These are caused by a hormone deficiency and are not pedagogically to regulate. Many children with Angelman syndrome at night must be fixed, eg by means of a shoulder - abdominal belt, so that they come to rest.

Despite the inability to learn rules just talking (on average, six words are spoken language articulated course ), people with Angelman syndrome are usually capable of simple, sometimes very subjective held gestures, for example, according to the principle of sign - supported communication ( GuK ) to learn to use images to communicate or use gestures for communication.

People with Angelman syndrome remain live long on the help of others. They are intellectually can be formed in different, but usually very limited, usually require special support and especially permanent staffing support in learning and the practical accomplishment of everyday life.

Many people with Angelman syndrome have a particular fondness for water. You like to go swimming, like to play with water and are fascinated by reflections on water or, for example, on glass surfaces. Also plastic, especially strong crackling material, such as plastic bags or packaging, exerts the most out of a strong fascination.

Often people consider with Angelman syndrome love pictures of herself and close friends or family.

Genetics

Angelman syndrome is caused by lack of expression of the UBE3A gene in the brain. The chromosome 15q11 - q13 portion of chromosome 15, on which this gene is located, is subject to so-called imprinting. This means that certain genes on this section only on the originating from the Father and others are active only on the originating from the parent chromosome. In Angelman syndrome, the maternal chromosome segment is not operational and the UBE3A gene on the paternal chromosome is shut down by imprinting; Thus, the gene is completely missing. Is not the mother, but the paternal chromosome segment in error, this leads to Prader -Willi syndrome.

At 50 to 80 of 100 people with Angelman syndrome the cause of the peculiarity lies in a deletion ( = item loss ) of the mother ( = maternal ) chromosome 15q11 - 15 in the region q13 (some with translocation ).

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

With eight to eleven out of 100 people with Angelman syndrome there is a mutation in the UBE3A gene on the maternal chromosome.

An error in the imprinting is detectable at about five in 100 people. This may be due to a mutation or due to epigenetic due to a mutation or deletion of the imprinting center. This is a segment of DNA, which (as DNA methylation) of seven genes on the paternal and maternal chromosome controls the differential epigenetic modification. This leads in each case to the activation or inactivation of the gene. The imprinting with the result that on the maternal chromosome the gene UBE3A is active and is expressed UBE3A is however inactive on the paternal chromosome. Is the function of the imprinting center is disturbed, this has a missing or faulty methylation patterns result, which can among other things have Angelman syndrome result.

The Angelman Syndrome may have a hereditary component. Parents are not affected, but have certain chromosomal features that increase the likelihood of conceiving a child with Angelman syndrome. This is reflected in the striking frequency of quasi affected siblings. A mutation in the UBE3A gene for instance, can be passed silently over generations through the male side of a family. Does the grandfather a mutation that he passes on to his daughter, this is also reflected in the subsidiary is not noticeable because the mutation is on the paternal chromosome. The daughter then has a 50% risk to bring a child with Angelman syndrome born.

Diagnosis

The diagnosis is made ( based on a cytogenetic or molecular genetic testing ) in the section between the third and seventh year by children € lodges (by striking EEG values ​​, regardless of epilepsy, even in sleep consisting ) or by geneticists:

It is possible to determine the Angelman syndrome in a subset of children affected by a genetic test, but not all, in which one starts from the clinical symptoms forth from the presence of the syndrome. A positive genetic test can therefore determine the Angelman syndrome with certainty, however, does not exclude a negative test it out.

In many cases, the parents of the child contact with the suspicion of Angelman syndrome at their pediatrician, as they have been informed by certain typical abnormalities in advance to find an explanation for their child's special features. Thus, the observation of the behavior and appearance of the child in the diagnosis can be a significant help.

Therapy

A Angelman syndrome is not incurable. Medically relevant is the adequate treatment of epilepsy often occur, squint (strabismus ) and the curvature of the spine (scoliosis ).

Otherwise, the most common extraction methods that have a positive impact on the development of children with Angelman syndrome, special education early intervention, motor therapy, physiotherapy, occupational therapy, speech therapy, sensory integration therapy and therapeutic riding. The special fondness for water can also be used therapeutically.

Life expectancy

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

Quotes

  • Every child is unique and different, and this also applies to these particular children. ( Marga Hogenboom, 2003, p 108 )
  • These children are very open and approachable. You like to take on eye contact, see everyone on with her blue eyes, so that one can imagine as if you fall into unexpected depths, as it meets with no resistance, no sign of antipathy in her eyes. ( Marga Hogenboom, 2003, p 104 )
Phonation Balance (ability) Humour Medical restraint Gene product Prader–Willi syndrome Deletion (genetics) Epigenetics Medical diagnosis Integrated Authority File
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