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%)
- 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.