Angelman syndrome

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Angelman's Syndrome ( US ) is a genetic disorder that primarily affects the nervous system. Symptoms include small head and special facial appearance, severe intellectual disability, developmental defects, speech problems, balance and motion problems, seizures, and sleep problems. Children usually have a happy personality and have a particular interest in water. The symptoms generally become apparent at one year of age.

Angelman's syndrome is usually due to a new mutation than one inherited from one's parents. Angelman's syndrome is due to the lack of functional chromosome part 15 that is inherited from one's mother. Most of the time, it is due to the removal or mutation of the UBE3A gene on that chromosome. Sometimes, it's because it inherits two copies of chromosome 15 from one's father and none of their mothers. Since the father version is inactive by a process known as genomic inclusion, there is no functional version of the remaining genes. The diagnosis is based on symptoms and possible genetic testing.

No drugs available. Treatment is generally supportive. Anti-seizure drugs are used in those with seizures. Physical and strengthening therapy can help with walking. Those affected have an almost normal life expectancy.

The US affects 1 in 12,000 to 20,000 people. Men and women alike are often affected. It's named after the British pediatrician, Harry Angelman, who first described the syndrome in 1965. The older term, "happy doll syndrome", is generally considered patronizing. Prader-Willi syndrome is a separate condition, caused by the loss of the same father's chromosome 15.

Video Angelman syndrome

Signs and symptoms

The following text lists the signs and symptoms of Angelman's syndrome and its relative frequency in affected individuals.

Consistent (100%)

• Developmental delay, functionally heavy
• Speech, no or little use of words; receptive and non-verbal communication skills are higher than verbal ones
• Movement or balance disorder, usually tremendous walking and/or tractional walking atazia
• The uniqueness of behavior: a combination of frequent laughter/smiles; a clear happy attitude; personality is easily aroused, often with the movement of the hands; hypermotoric behavior; short attention span

Frequent (over 80%)

• Delay, disproportionate growth in head circumference, usually produces microcephaly (absolute or relative) by age 2
• Seizures, onset usually less than 3 years
• EEG abnormal, characteristic pattern with slow wave spikes large amplitude

Related (20-80%)

Maps Angelman syndrome

Pathophysiology

Angelman's syndrome is caused by the loss of normal mother's contribution to the region of chromosome 15, most often with the removal of that chromosome segment. Other causes include uniparental disomy, translocation, or single gene mutations in the region. The healthy person receives two copies of chromosome 15, one from the mother, the other from the father. However, in the chromosomal region of great importance to Angelman's syndrome, maternal and paternal contributions express specific genes differently. This is due to the epigenetic printing of certain sexes; the biochemical mechanism is DNA methylation. In normal individuals, maternal alleles of the UBE3A gene, part of the ubiquitin pathway, are expressed and the paternal allele is specifically silenced in the developing brain. In the hippocampus and cerebellum, maternal alleles are almost exclusively active. If mother's contribution is lost or mutated, the result is Angelman's syndrome. (Some other genes on chromosome 15 are printed maternally, and when the father's contribution is lost, by the same mechanism, the result is Prader-Willi syndrome.) Methylation tests performed for Angelman's syndrome (defects in UBE3A) seek methylation in neighboring SNRPN gene silenced by methylation on maternal gene copies).

While Angelman's syndrome can be caused by a single mutation in the UBE3A gene, the most common genetic defect that leads to Angelman's syndrome is the maternal delpass (mega base) ~ mega 4Mb in the chromosome region 15q11-13 causing the absence of UBE3A expression in areas of the brain colored by the father. UBE3A code for E6-AP ubiquitin ligase, which selects its substrate is highly selective, and four identified E6-AP substrates have given light to the molecular mechanisms that may underlie Angelman's syndrome in humans.

Early studies on mice that did not express the mother UBE3A showed severe disorders in the formation of hippocampus memory. In particular, there is a deficit in the paradigm of learning that involves the conditioning of contextual fears that depend on the hippocampus. In addition, the maintenance of long-term synaptic plasticity in the hippocampal CA1 in vitro is disrupted by the rat Ube3a ^-/- . These results provide a link between the plasticity of hippocampal synapsis in vitro , the formation of memory that depends on the hippocampus , and the molecular pathology of Angelman's syndrome.

Neurophysiology

Electroencephalogram (EEG) in the US is usually abnormal, more than clinically estimated. This EEG facilitates a US differential diagnosis, but is not pathognomonic. Three different interictal patterns are seen in this patient. The most common pattern is a very large rhythm 2-3 Hz rhythm that is most prominent in lead prefrontal. The next most common is the high-voltage rhythm 4-6Ã, Hz symmetrical. The third pattern, 3-6 Hz activity interspersed by spikes and sharp waves in the occipital lead, is associated with eye closure. Paroxysms laughter has nothing to do with EEG, overriding this feature as a gelastic phenomenon.

EEG anomalies can be used as quantitative biomarkers to "map US development and as a clinical outcome measure".

It seems that the neurons of people with Angelman syndrome are formed correctly, but they can not function properly.

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Diagnosis

The diagnosis of Angelman syndrome is based on:

• History of delayed motor milestones and later delays in general progress, especially conversation
• Unusual movements include fine tremor, thorn extremity movements, flapping hands, and a wide, stiff walking style.
• A typical facial appearance (but not in all cases).
• Abnormal epileptic history and EEG search.
• Happy gestures with frequent laughs
• Removal or inactivity on chromosome 15 by comparative genomic hybridization array (aCGH) or with BACs-on-Beads technology.

The diagnostic criteria for this disorder were originally established in 1995 in collaboration with the Angelman Syndrome Foundation (USA); this criterion was revised in 2005.

Seizures are a consequence, but so is excessive laughter, which is a major obstacle to early diagnosis.

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Treatment

There are currently no medications available. Epilepsy can be controlled by using one or more anticonvulsant drugs. However, there is difficulty in ensuring the level and type of anticonvulsant drugs necessary to establish control, because the US is usually associated with having several seizure varieties, not just those as in normal cases of epilepsy. Many families use melatonin to promote sleep in conditions that often affect sleep patterns. Many individuals with Angelman's syndrome sleep for a maximum of five hours at a time. Lightweight laxatives are also often used to encourage regular bowel movements, and early intervention with physiotherapy is important to encourage joint mobility and prevent joint stiffness. Speech and Language Therapy is commonly used to help individuals with Angelman syndrome and their communication problems.

Those with syndrome are generally happy and contented people who love to contact and play human beings. People with the US show a deep desire for personal interaction with others. Communication can be difficult at first, but as children with AS develop, there is a definite character and ability to make themselves understood. People with AS tend to develop strong non-verbal skills to compensate for the use of their limited words. It is widely accepted that their understanding of communication directed to them is much greater than their ability to return the conversation. Most affected people will not develop more than 5-10 words, if any.

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Prognosis

The severity of the symptoms associated with Angelman's syndrome varies significantly across all of their affected populations. Some speeches and a greater level of self-care may occur among the most profoundly affected. Walking and use of simple sign language may be beyond the reach of more depth. Early and advanced participation in physical, occupational (related to the development of fine motor control skills), and communication (speech) therapy are believed to significantly improve the prognosis (in the field of cognition and communication) of individuals affected by the US. Furthermore, the specific genetic mechanisms underlying this condition are thought to correlate with the general prognosis of the affected person. At one end of the spectrum, mutations to the UBE3A gene are considered to be correlated with the least affected, whereas greater deletion on chromosome 15 is thought to be related to the most affected.

Clinical features of Angelman syndrome change with age. As adults age, hyperactivity and poor sleep patterns improve. Seizures decrease in frequency and often stop completely and EEG abnormalities are less clear. Medication is usually recommended for those with seizure disorders. Often overlooked is the contribution of poor sleep patterns to frequency and/or severity of seizures. Medication may be helpful to help deal with this problem and improve the prognosis associated with seizures and sleep. Also noteworthy is the report that the frequency and severity of seizures increased temporarily in girls of pubic Angelis syndrome, but did not appear to affect long-term health. Facial features remain recognizable with age, but many adults with US look very young for their age.

Puberty and menstruation begin around the mean age. Sexual development is considered unaffected, as evidenced by one case reported from a woman with Angelman syndrome containing a girl who also has Angelman's syndrome.

The majority of them with AS achieve continuity during the day and some at night. Angelman's syndrome is not a degenerative syndrome, and thus people with AS can improve their life skills with support.

The skills of dressing vary and are usually limited to clothing without buttons or zippers. Most adults can eat with knives or spoons and forks, and can learn to perform simple household tasks. Public health is quite good and life span is close to the average. Specific problems that occur in adults are the tendency for obesity (more in women), and worsening scoliosis if present. The affectionate nature that is also a positive aspect in younger children may also persist in adult life where it can cause social problems, but this problem can not be overcome.

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Epidemiology

Although the prevalence of Angelman's syndrome is not known for certain, there are some estimates. The best available data are from studies of school-aged children, aged 6-13 years, living in Sweden and from Denmark where the diagnosis of US children in medical clinics compared to the 8-year period is about 45,000 births. Swedish studies show a US prevalence of about 1/20,000 and Danish studies show a minimal US prevalence of about 1/10,000.

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History

Harry Angelman, a pediatrician working in Warrington, England, first reported three children with this condition in 1965. Angelman later described his choice under the title "Wayang Anak" to describe these cases as related to the oil paintings he saw while on vacation in Italy:

Medical history is full of interesting stories about disease discovery. The story of Angelman syndrome is one such story. It was pure coincidence that almost thirty years ago (for example, around 1964) three disabled children were treated at various times to my children's wards in England. They have various defects and although at first glance they seem to be suffering from different conditions I feel that there is a common cause for their illness. The diagnosis was purely pure because despite the now smoother technical investigation, I could not establish any scientific evidence that the three children had the same disability. In this view I hesitate to write about them in medical journals. However, while on vacation in Italy, I happened to see an oil painting at the Castelvecchio Museum in Verona called... Boy with a Doll. The face of the laughing boy and the fact that my patient showed a jerky motion gave me the idea to write an article about three children with a Wayang Anak title. It is not a name that pleases all parents but it serves as a way of combining three small patients into one group. Then the name was changed to Angelman's syndrome. This article was published in 1965 and after some initial interest was dormant almost until the early eighties.

Case reports from the United States first began to appear in the medical literature in the early 1980s. In 1987, it was first noted that about half of children with AS had a small chromosome 15 missing ( partial removal chromosome 15 ).

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Society and culture

Many poems in Richard Price 's Hand Held poems (1997), Lucky Day (2005), and Small World (2012) reflect the disability of the poetess's daughter , which has Angelman's syndrome. In the Philippine drama series 2011 Budoy , the main titular character and protagonist Budoy Maniego (played by Filipino actor Gerald Anderson) was diagnosed with Angelman syndrome.

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References

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External links

• Angelman Syndrome Foundation US
• Angelman AUS Syndrome Association
• Angelman Syndrome Education Support & amp; Research Trust - English
• Foundation for Angelman Syndrome Therapy
• Angelman's Syndrome in Curlie (based on DMOZ)
• GeneReviews/NCBI/NIH/UW is included in Angelman syndrome

Source of the article : Wikipedia