Patients diagnosed with Angelman syndrome will commonly present with the following signs and symptoms:
Entire Body System
- Developmental Delay
Behavioral therapy: This will help children with Angelman syndrome to control hyperactivity and hasten developmental delays. [symptoma.com]
A typical EEG pattern and microcephaly in patients with developmental delay prompt for AS investigation while wide genetic screening should be applied to help resolution of the complex phenotypes characterized by developmental delay. [ncbi.nlm.nih.gov]
Most individuals with Angelman syndrome will have severe developmental delays, speech limitations, and motor difficulties. [medicinenet.com]
RESULTS: All patients with AS based on a deletion had epilepsy. Epilepsy was present in 3/4 children with UBE3A mutation, and 4/5 with pUPD. Onset of epilepsy occurred earlier in deletion cases compared to pUPD or UBE3A mutations cases. [ncbi.nlm.nih.gov]
This condition is a neurogenetic disorder characterised by developmental delay, absence of speech, motor impairment, epilepsy and a peculiar behavioural phenotype. [amazon.co.uk]
- Cerebral Palsy
Beyond individual situations, Angelman syndrome can serve as a disease model opening broad questioning of genetic and epigenetic influences in neurology, as well as of several concepts such as psychomotor development, cerebral palsy, behavioural phenotypes [amazon.co.uk]
It is often misdiagnosed as cerebral palsy or autism because of lack of awareness. Although presumed to be initially rare, thousands of other cases have gone undiagnosed or misdiagnosed as cerebral palsy, autism, or other childhood disorders. [achievementcenteroftexas.org]
Angelman syndrome — codes and concepts open Angelman syndrome is a rare neurological disorder which occurs in 1 out of every 15,000 births and in the past, was mistaken for other disorders like cerebral palsy or autism. [dermnetnz.org]
- Feeding Difficulties
Complications Complications associated with Angelman syndrome include: Feeding difficulties. Difficulty coordinating sucking and swallowing may cause feeding problems in infants. [mayoclinic.org]
Children with Angelman syndrome may have feeding difficulties, sleep problems and hyperactivity. Feeding difficulties, such as problems sucking and swallowing, may occur during the first few months of life. [childrenshospital.org]
Feeding difficulties in young infants and obesity in late childhood can also be seen. [ncbi.nlm.nih.gov]
People with the disorder have feeding difficulties as infants and noticeable delayed development around 6-12 months of age. They need intensive therapies to help develop functional skills. AS affects every race and both genders. [cureangelman.org]
The junctions where these arteries come together may develop weak spots. These weak spots can balloon out and fill with blood, creating the outpouchings of blood vessels known as aneurysms. [medicinenet.com]
Babies born with PWS have poor muscle tone and a weak cry. They initially are slow feeders and appear undernourished. The feeding problems improve after infancy. [stanfordchildrens.org]
These include: smoking high blood pressure a family history of brain aneurysms In some cases, an aneurysm may develop because there was a weakness in the walls of the blood vessels at birth. [nhs.uk]
- Heart Disease
However, congenital structural anomalies including Hirschsprung disease, congenital heart disease, and corpus callosum hypoplasia were far more common in Mowat-Wilson Syndrome than in AS. [hindawi.com]
Wilson in 1998.  Presentation [ edit ] This autosomal dominant disorder is characterized by a number of health defects including Hirschsprung's disease, intellectual disability, epilepsy,  delayed growth and motor development, congenital heart disease [en.wikipedia.org]
This product also reduces the risk of heart disease and plaque formation, successfully fights cholesterol and its effects. [angelmanforum.org]
Other factors may include: a diet high in fats and cholesterol a family history of heart conditions, including heart disease and heart attack smoking obesity pregnancy, which may increase your risk of having an aneurysm of the spleen The diagnostic tools [healthline.com]
Jaw & Teeth
Most patients of this age group show at least 8 of the major characteristics (bursts of laughter, happy disposition, hyperactive behaviour, microcephaly, brachycephaly, macrostomia, tongue protrusion, mandibular prognathism, widely spaced teeth, stiff [ncbi.nlm.nih.gov]
[…] age, absent speech (or speech limited to less than six words), jerky movements with an ataxic gait if the patient is walking, paroxysm of inappropriate laughing, dysmorphic craniofacial features (brachycephaly, mid-facial hypoplasia, deep set eyes, macrostomia [pesquisa.bvsalud.org]
[…] head), ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia (floppiness), hyperactivity, seizures, absence of speech, frequent smiling and outbursts of laughter, and an unusual facies (facial appearance) characterized by macrostomia [bibliomed.org]
Generally from 1 year of age, the typical features of AS develop: severe intellectual deficit, absent speech, outbursts of laughter with hand flapping, microcephaly, macrostomia, maxillary hypoplasia, prognathia and neurological problems with a puppet-like [orpha.net]
- Chewing Problem
frequent chewing Problems feeding for infants Frequent drooling Wide mouth and wide spaced teeth, Decreased tone in muscles of the trunk Changes in the color of the skin lighter than expected, light hair and eye color (compared to family) Problems with [epilepsy.com]
- Muscle Hypotonia
Cerebellar ataxia, muscle hypotonia and tremor, though constant in childhood, tend to be attenuated in adulthood. [ncbi.nlm.nih.gov]
HYPOTONIA ; and a peculiar facies. [hon.ch]
A dictionary of medical eponyms Related people Harry Angelman A chromosome 15 disorder comprising microcephaly with mental and motor retardation, epilepsy, ataxic gait or complete inability to walk, muscle hypotonia, EEG abnormalities, and peculiar [whonamedit.com]
- Easily Excitable
Their behavior may combine frequent laughter and smiling, an easily excitable personality, hand flapping movements, hyperactive behavior, and a short attention span. [omicsonline.org]
Behavioral uniqueness - any combination of frequent laughter/smiling, apparent happy demeanor, easily excitable personality, often with hand flapping movements. [achievementcenteroftexas.org]
Children with Angelman syndrome may be easily excited, hypermotoric and hyperactive. They are active explorers and often may appear to be constantly in motion. [web.archive.org]
excitable personality, often with hand flapping movements; hypermotoric behaviour; short attention span Frequent (more than 80%) Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2 [angelmanuk.org]
They are easily excitable and have frequent episodes of laughter and smiling, even during inappropriate times. [pedclerk.bsd.uchicago.edu]
- Inappropriate Laughter
Angelman syndrome is characterized by mental retardation, seizures, ataxia, inappropriate laughter, lack of speech, a particular facial appearance, and generally a chromosome 15q11-q13 deletion. [ncbi.nlm.nih.gov]
Excessive and inappropriate laughter is a telltale sign. The actual number of cases of Angelman syndrome is unknown. Some estimates are 1 in 15,000 babies have Angelman syndrome. Others estimate 1 in 30,000. [mentalhelp.net]
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. [symptoma.com]
By age 2-3 years, more than 80% of patients have seizures and abnormal EEGs with large amplitudes and slow spiked waves, even in the absence of active seizures. [pedclerk.bsd.uchicago.edu]
Majority of patients with Angelman syndrome will have microcephaly and recurrent bouts of seizures that starts beyond the age of two years old. [symptoma.com]
Seizures in AS are usually controllable with one or more anti-seizure medications. In some individuals with severe seizures, dietary manipulations may be tried in combination with medication. [encyclopedia.com]
Seizures Seizures are present in 85% of patients within the first three years of life[ 17 ], although less than 25% develop seizures during the first year[ 18 ]. [ijponline.biomedcentral.com]
Often, patients will become less excitable as they age and they outgrow sleep cycle abnormalities. Self-skin examination New smartphone apps to check your skin Learn more (Sponsored content) Related information [dermnetnz.org]
“As a clinician this is equally exciting from a clinical trial feasibility standpoint.” [innovationdistrict.childrensnational.org]
Children with Angelman syndrome have global developmental delays, seizures and excitable, happy personalities as a general rule. What causes Angelman syndrome? Angelman syndrome is a genetic disorder. [nicklauschildrens.org]
In 1965, Angelman described 3 cases of what he called "Puppet" children, named for the characteristic signs associated with what is now known as Angelman syndrome, including mental retardation, speech impairment, easy excitability, and frequent spontaneous [ncbi.nlm.nih.gov]
Dr Dora Markati, co-investigator of the trial said: “We are really excited to have dosed the first study participant with a promising potential treatment. [paediatrics.ox.ac.uk]
- Abnormal Sleep-Wake Cycles
Sleep disorders are also common, often characterized by abnormal sleep-wake cycles. Movement disorders are nearly universal in Angelman syndrome, most frequently presenting with ataxia and tremor. [ncbi.nlm.nih.gov]
Other characteristics noted in over 80% of patients include microcephaly, seizures, and a specific, abnormal EEG pattern. Patients may also exhibit wide mouths with unusual tongue/mouthing behaviors, hypopigmentation, and abnormal sleep-wake cycles. [dnatesting.uchicago.edu]
Sleep disturbances such as a decreased need for sleep and disrupted or abnormal sleep/wake cycles (e.g., awaking at night or rising earlier than normal) are frequent findings in children with Angelman syndrome. [web.archive.org]
Sleep Sleep disorders are also common, often characterised by abnormal sleep-wake cycles. [ 6 ] The sleep disorders may be related to abnormal serum melatonin profiles. [ 7 ] Poor sleep does not significantly interfere with daytime alertness. [patient.info]
The patient demonstrated generalized prolonged myoclonus severe enough to produce temperatures of 41.4 degrees C and CPK elevations to 7281 U/l. This myoclonus was unresponsive to benztropine, clonazepam and worsened with bromocriptine. [ncbi.nlm.nih.gov]
Danielle M Andrade, Clement Hamani and Berge A Minassian, Treatment options for epileptic myoclonus and epilepsy syndromes associated with myoclonus, Expert Opinion on Pharmacotherapy, 10, 10, (1549), (2009). Gregor D. Gilfillan, Kaja K. [doi.org]
Diminished muscle tone (hypotonia) of the trunk, increased muscle tone (hypertonia) of the arms and legs, and abnormally exaggerated or brisk reflex responses (hyperreflexia) may also occur. [web.archive.org]
Over time, increased muscle tone in the arms and legs coupled with decreased muscle tone in the trunk will lead to hyperreflexia (exaggerated or repeating reflex responses). Another characteristic neurological symptom is seizures. [verywellhealth.com]
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:
- Chromosome analysis or karyotyping: This is the direct microscopic examination of the chromosomes to determine and identify any defects in the morphology and size of the sampled chromosomes.
- Fluorescence in situ hybridization (FISH): This fluorescence assay will demonstrate the defective long arm of chromosome 15 in Angelman syndrome.
- DNA methylation test: This test reveals any gene imprinting defects by the use of methylation techniques. Angelman syndrome will show the absence of the maternal gene copy and expression within the brain tissues.
- UBE3A gene sequencing: This a specific test that demonstrates the presence of gene mutation within the maternal copy of the gene found in a chromosome subset.
- Excessive Drooling
Additional findings include excessive drooling, crossed eyes (strabismus), lack of normal color of the (hypopigmentation) of the skin, eyes and hair due to lack of certain melanin pigments. [web.archive.org]
drooling fast and involuntary eye movements (nystagmus) Angelman syndrome is caused by a change involving the gene E3 ubiquitin protein ligase (UBE3A). [healthline.com]
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:
- Anti-convulsant medications: This therapy is given to control the seizure disorders associated with Angelman syndrome.
- Physical therapy: Patients with Angelman syndrome may learn to walk promptly and balance with the help of physical therapy and rehabilitation.
- Speech therapy: Speech therapy among patients with the syndrome may hasten communication problems. Patients may be taught sign language if verbal communication is not achieved .
- Behavioral therapy: This will help children with Angelman syndrome to control hyperactivity and hasten developmental delays.
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 .
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 .
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 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). 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.
- Williams CA, Zori RT, Hendrickson J. Angelman syndrome. Curr Probl Pediatr 1995; 25(7): 216–231.
- Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 1997; 15(1): 70–73.
- Cox GF, Bürger J, Lip V. Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am J Hum Genet 2002; 71(1): 162–164.
- Doornbos ME, Maas SM, McDonnell J, Vermeiden JP, Hennekam RC. Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study. Hum Reprod 2007; 22(9): 2476–2480.
- White HE, Durston VJ, Harvey JF, Cross NC. Quantitative analysis of SRNPN gene methylation by pyrosequencing as a diagnostic test for Prader-Willi syndrome and Angelman syndrome. Clin. Chem. 200 652 (6): 1005–13.
- Dan, B., Angelman syndrome: Current understanding and research prospects. Epilepsia, 2009. 50(11): p. 2331–2339.
- Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF. Angelman syndrome in adulthood. Am. J. Med. Genet. 1996 66 (3): 356–60.
- Williams CA, Angelman H, Clayton-Smith J et al. Angelman syndrome: consensus for diagnostic criteria. Angelman syndrome Foundation. Am. J. Med. Genet. 1995 56.
- Buntinx IM, Hennekam RC, Brouwer OF et al. Clinical profile of Angelman syndrome at different ages. American Journal of Medical Genetics 1995 56 (2): 176–83.
- Andersen WH, Rasmussen RK, Strømme P. Levels of cognitive and linguistic development in Angelman syndrome: a study of 20 children. Logopedics, phoniatrics, vocology 2001 26 (1): 2–9.