what Is a Angelman Syndrome

ANGELMAN SYNDROME

Definition:-

Angelman syndrome is a genetic disorder that causes developmental disabilities and neurological problems, such as difficulty speaking, balancing and walking and, in some cases, seizures. Frequent smiles and outbursts of laughter are common for people with Angelman syndrome, and many have happy, excitable personalities.

Angelman syndrome usually isn't detected until parents begin to notice developmental delays when a baby is about 6 to 12 months old. Seizures often begin when a child is between 2 and 3 years old.

People with Angelman syndrome tend to live a normal life span, but they may become less excitable with age. Other signs and symptoms remain. Treatment for Angelman syndrome focuses on managing the child's medical and developmental problems. Consult to Breast Cancer Specialist in Central Delhi for best treatment .

Causes

Angelman syndrome is a genetic disorder. It's most often caused by problems with a gene located on chromosome 15 called the ubiquitin-protein ligase E3A (UBE3A) gene.

Genes are segments of DNA that provide the blueprints for all of your characteristics. You receive your genes, which occur in pairs, from your parents. One copy comes from your mother (maternal copy), and the other copy comes from your father (paternal copy). Consult to Breast Cancer Specialist in East Delhi and Breast Cancer Specialist in North Delhi for best treatment.

A missing or defective gene: Both genes in a pair usually are active. This means that your cells use information from both the maternal copy and the paternal copy of each gene pair. But in a small number of genes, only one copy of a gene pair is active. The activity of each gene copy depends on whether it was passed from your mother or from your father. This parent-specific gene activity is called imprinting. In these genes, when the copy that's usually active is missing or defective, it causes problems in the functions and characteristics controlled by that gene. Consult to Breast Cancer Specialist in South Delhi and Breast Cancer Specialist in West Delhi for best treatment.

Normally, only the maternal copy of the UBE3A gene is active in the brain, caused by what's known as genomic imprinting. Most cases of Angelman syndrome occur when part of the maternal chromosome 15, which contains this gene, is missing or damaged. In a small number of cases, Angelman syndrome is caused when two paternal copies of the gene are inherited, instead of one paternal and one maternal copy (paternal uniparental disomy).

Risk factors

Angelman syndrome is rare. In most cases, researchers don't know what causes the genetic changes that result in Angelman syndrome. Most people with Angelman syndrome don't have a family history of the disease. In a small percentage of cases, however, Angelman syndrome may be inherited from a parent, so a family history of the disease may increase a baby's risk of developing Angelman syndrome.

Signs and symptoms

The following list features of Angelman syndrome and their relative frequency in affected individuals.

Consistent (100%)

• Developmental delay, functionally severe
• Speech impairment, no or minimal use of words; receptive and non-verbal 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

Frequent (more than 80%)

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

Associated (20 - 80%)

• Strabismus
• Hypo pigmented skin and eyes
• Tongue thrusting; suck/swallowing disorders
• Hyperactive tendon reflexes
• Feeding problems during infancy
• Uplifted, flexed arms during walking
• Prominent mandible
• Increased sensitivity to heat
• Wide mouth, wide-spaced teeth
• Sleep disturbance
• Frequent drooling, protruding tongue
• Attraction to/fascination with water
• Excessive chewing/mouthing behaviors
• Flat back of head
• Smooth palms

Diagnosis

The diagnosis of Angelman syndrome is based on:

• A history of delayed motor milestones and then later a delay in general development, especially of speech
• Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait.
• Characteristic facial appearance (but not in all cases).
• A history of epilepsy and an abnormal EEG tracing.
• A happy disposition with frequent laughter
• A deletion or inactivity on chromosome 15 by array comparative genomic hybridization (aCGH) or by BACs-on-Beads technology.

Diagnostic criteria for the disorder were initially established in 1995 in collaboration with the Angelman syndrome Foundation (USA); these criteria have undergone revision in 2005.

Tests:

A combination of genetic tests can reveal the chromosome defects related to Angelman syndrome. These tests may look at:

• Chromosome size, shape and number: This test, known as chromosome analysis (karyotyping), examines chromosomes in a cell sample.
• Missing chromosomes: Known as fluorescence in situ hybridization (FISH), this test can show if portions of any chromosomes are missing.
• Parental DNA pattern: This test, known as a DNA methylation test, reveals a gene's imprinting pattern. Normal results show both a paternal and maternal DNA pattern — meaning genes from both parents are active. In some areas of the brain, only the maternal gene is active. In most cases for people with Angelman syndrome, the maternal copy of the gene is lost, so there are no copies of the gene operating in the brain.
• Gene mutation: Rarely, Angelman syndrome may occur when a person's maternal copy of the UBE3A gene is active, but mutated. If results from a DNA methylation test are normal, your child's doctor may order a UBE3A gene sequencing test to look for a maternal mutation.

Treatment

There is currently no cure available. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because AS is usually associated with having multiple varieties of seizures, rather than just the one as in normal cases of epilepsy. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Many individuals with Angelman syndrome sleep for a maximum of 5 hours at any one time. Mild laxatives are also used frequently to encourage regular bowel movements and early intervention with physiotherapy is important to encourage joint mobility and prevent stiffening of the joints.

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

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

Drugs:

Medications that are commonly prescribed include sodium valproate (Epilim), clonazepam (Rivotril), lamotrigine (Lamictal), carbamazepine (Tegretol). The new antiepileptic drug, levetiracetam (Keppra) may also be helpful, particularly in treating the myoclonic seizures. Another medication called piracetam (Nootropil) may also be effective in controlling the jerky movements.

Alternatives:

There are no alternatives recommended for angelman syndrome

Complications

Complications associated with Angelman syndrome include:

• Feeding difficulties. Some infants with Angelman syndrome have problems feeding during the first few months of life because of an inability to coordinate sucking and swallowing. If your child has difficulty feeding, your pediatrician may recommend a high-calorie formula to help your baby gain weight.
• Hyperactivity. Many young children with Angelman syndrome have increased motor activity. They may move quickly from one activity to another, often keeping their hands or a toy in their mouths. Their attention span may be very short. Hyperactivity often decreases with age in children with Angelman syndrome, and medication usually isn't necessary.
• Sleep disorders. It's common for people with Angelman syndrome to have abnormal sleep-wake patterns and to need less sleep than normal. In some cases, sleep difficulties may improve with age. Medication and behavior therapy may help control sleep disorders.
• Curving of the spine (scoliosis). Some people with Angelman syndrome develop this abnormal side-to-side spinal curvature over time.
• Obesity. Older children with Angelman syndrome tend to have large appetites, which lead to obesity.

Prevention

In rare cases, Angelman syndrome may be passed from affected parent to child through defective genes. If you're concerned about a family history of Angelman syndrome, or if you already have a child with Angelman syndrome, you may wish to talk to your doctor or a genetic counselor for help planning future pregnancies.