Angelman syndrome is a rare genetic disorder characterized by severe intellectual and developmental disability, sleep disorder, frequent and sometimes inappropriate laughter, seizures, jerky movements and ataxia. It is named after the British pediatrician, Dr. Harry Angelman, who first described it in 1965.
The disease is related to the following processes: congenital and has an incidence of about 0 / 100.000.
Angelman syndrome is an uncommon genetic disorder presenting with developmental delays and neurologic impairments. Patients with Angelman syndrome are observably happy and excitable people with frequent outburst of laughter . Developmental delays with this syndrome are observable between the first 6 to 12 months of life while seizure ensues around 2 to 3 years of age. Majority of patients with Angelman syndrome will have microcephaly and recurrent bouts of seizures that starts beyond the age of two years old.
Despite their coarse anatomic features and severe neurologic impairments, patients suffering from Angelman syndrome have a comparatively similar life expectancy compared to the normal population. The goal in the management of Angelman syndrome focuses on the patient’s neurological dysfunctions and developmental delays.
Angelman syndrome results from the maternal gene deletion of the locus UBE3A located at the long arm of chromosome 15 (15q11-13) . Studies have demonstrated that Angelman syndrome is closely associated with the intracytoplasmic sperm injection (ICSI) procedures with in vitro fertilization (IVF) techniques used for male infertility . The genetic etiology in Angelman syndrome is brought about by the imprinting defects during the DNA gene expression of the maternal chromosome subset.
The international incidence of Angelman syndrome as a molecular gene defect is approximately 1 case per 300,000 genetic diseases. The syndrome is further evident with an overall incidence rate of 1 case per 12,000 to 20,000 population. Mothers undergoing assistive IVF hormonal steroid therapy have an increased risk of giving birth to an infant afflicted with Angelman syndrome to more than 12.5 times compared to normal unassisted births .
The main pathophysiology of Angelman syndrome stems out from the absence of the maternal gene contribution in the long arm of the chromosome 15 . Other possible genetic causes of the syndrome include genetic translocation, uniparental disomy, and single gene mutation within the chromosome. The subsequent deletion of the gene within the long arm of chromosome 15 will result in the non-expression of the UBE3A gene needed in the DNA methylation during the ubiquitin pathway.
Recent studies have postulated that the absence of the UBE3A gene will lead to the impairment of the hippocampus memory and cognitive functioning that assists in the learning process, and the synaptic plasticity that controls movements and balance. One of the pathognomonic signs of Angelman syndrome is the characteristic electroencephalogram changes in the prefrontal leads suggesting that the pathogenesis of the syndrome could possibly be associated with some abnormalities in the neurophysiology of the brain .
The majority of patients with Angelman syndrome will have progressive developmental delay, speech dysfunctions, and motor difficulties till adulthood. However, these patients will have a normal lifespan without any developmental regression as they chronologically age. The prompt diagnosis of Angelman syndrome coupled with a customized interventional therapy and support improves the prognosis among patients. Female patients with Angelman syndrome have been observed to be prone to obesity and worsening of scoliosis .
Patients diagnosed with Angelman syndrome will commonly present with the following signs and symptoms:
Children with Angelman syndrome will typically present clinically with obvious developmental delays, microcephaly, movement disorders, impaired balance, and seizure disorders. This constellation of signs and symptoms is very suggestive of the syndrome clinically. The following tests may be used to confirm the diagnosis of Angelman syndrome:
The gene defect in Angelman syndrome is irreparable; thus, there is no known cure for this rare syndrome. Treatment will only focus on the management of the medical and developmental problems of the affected child. Because of the complexity of the problems involved in Angelman syndrome, a multidisciplinary approach is often times imperative in the management of the disease. The following treatment modalities are available for Angelman syndrome:
In few cases of Angelman syndrome, there has been an observable genetic transmission pattern noted. Genetic counselling may be needed to prevent the recurrence of the disease in the family lineage.
Angelman syndrome is a rare genetic disorder characterized by intellectual disability, developmental delay, microcephaly, speech impairment, and movement disorders.
Angelman syndrome results from the maternal gene deletion of the locus UBE3A located at the long arm of chromosome 15 (15q11-13). Some less common genetic causes include genetic translocation, uniparental disomy, and single gene mutation.
Patients will physically present with microcephaly, with observable speech, developmental, and movement impairments.
Clinical history, physical examination and neurologic examinations may clinch the diagnosis of Angelman syndrome. Confirmatory test like karyotyping, FISH, DNA methylation tests, and gene sequencing may also be implored.
Treatment and follow-up
Patients are treated with anti-convulsant therapy, physical and speech therapy, and behavioral therapy.