Angelman Syndrome: A Case Series Assessing Neurological Issues in Adulthood

Giroud, M.; Daubail, Benoît; Khayat, N.; Chouchane, Mondher; Berger, Eric; Muzard, E.; Bustos, Elisabeth Medeiros de; Thauvin‐Robinet, Christel; Faivre, Laurence; Masurel, Alice; Darmency-Stamboul, Véronique; Huet, Frédéric; Béjot, Yannick; Giroud, Maurice; Moulin, Thierry

doi:10.1159/000369454

Cited by 12 publications

(9 citation statements)

References 25 publications

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“…Several studies in AS reported severe seizures in early childhood with a distinct improvement during later childhood [61][62][63]. Seizure remission in late teens and early twenties followed by recurrence of seizures in third or fourth decades has been reported [64].…”

Section: Discussionmentioning

confidence: 99%

Epilepsy in Angelman syndrome: A scoping review

Samanta

2021

Brain and Development

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Angelman Syndrome (AS) is characterized by severe developmental delays including marked speech impairment, movement abnormalities(ataxia, tremor), and unique behaviors such as frequent laughter and is caused by dysfunctional maternal UBE3A gene (maternal 15q11-13 deletions, maternal specific UBE3A mutation, uniparental disomy, and imprinting defect). Intractable epileptic seizures since early childhood with characteristic EEG abnormalities are present in 80-90% patients with AS. Underlying pathophysiology may involve neocortical and thalamocortical hyperexcitability secondary to severe reduction of GABAergic input, as well as dysfunctional synaptic plasticity, deficient synaptogenesis, and neuronal morphological immaturity. The onset of epilepsy is most prevalent between 1 and 3 years of age; however, approximately 25% of patients developed epilepsy before one year of age. Various types of generalized seizures are most prevalent, with most common types are myoclonic and atypical absence. More than 95% of epilepsy patients may have daily seizures at least for a limited time during early childhood, and two-third patients develop disabling seizures. Fever provoked seizures, and frequent occurrence of nonconvulsive status epilepticus are two unique features. Seizures are frequently pharmacoresistant. Considering underlying prominent GABAergic dysfunction, clinicians had used AEDs that target GABAergic signaling such as valproate, phenobarbital, and clonazepam as first-line therapies for AS. However, due to the unfavorable side effect profile of these AEDs, a recent treatment approach involves priority use of levetiracetam, clobazam, topiramate, lamotrigine, ethosuximide, VNS, and carbohydrate-restricted diets. Besides symptomatic management, there has been recent progress to find a curative treatment with the following approaches: 1. Gene/protein replacement therapy (Adeno and lentiviral vector therapy to deliver a gene or secretory protein); 2. Activation of the intact but silent paternal copy of UBE3A (antisense oligonucleotide therapy and artificial transcription factors); and 3. Downstream therapies (OV101/gaboxadol, ketone supplement, novel compounds/peptides, anti-inflammatory/regenerative therapy).

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Section: Discussionmentioning

confidence: 99%

Epilepsy in Angelman syndrome: A scoping review

Samanta

2021

Brain and Development

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“…Anxiety and other behavioral issues can have a significant impact on quality of life for adults with AS. Although, behavioral issues appear to decrease with age, anxiety becomes significantly more prevalent (Giroud et al, ; Larson et al, ; Thibert et al, ). In this cohort, 57% had a history of anxiety symptoms that impact day‐to‐day function and quality of life.…”

Section: Discussionmentioning

confidence: 99%

“…As the first generations of individuals diagnosed with AS in childhood are now aging into adulthood, we are continuing to learn how to optimize their care. To date, there have been multiple case reports characterizing AS in adulthood (Buntinx et al, ; Clayton‐Smith, ; Giroud et al, ; Laan et al, ; Larson et al, ; Sandanam et al, ). We completed a large interview series with caregivers in 2015 to help characterize the impact of age and genotype on clinical outcomes for adolescents and adults with AS (Larson et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…We completed a large interview series with caregivers in 2015 to help characterize the impact of age and genotype on clinical outcomes for adolescents and adults with AS (Larson et al, ). Giroud et al () and Clayton‐Smith () performed retrospective case series of adult patients in which they assessed neurological parameters such as epilepsy and tremor. Clayton‐Smith analyzed neurological parameters as well as general health, behavioral issues, communication, and self‐help skills.…”

Section: Introductionmentioning

confidence: 99%

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Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases

Prasad

Grocott

Parkin

et al. 2018

American J of Med Genetics Pt A

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Angelman syndrome is a neurogenetic disorder with varying clinical presentations and symptoms as the individual ages. The goal of this study was to characterize changes over time in the natural history of this syndrome in a large population. We reviewed the medical records of the 53 patients who were born prior to 2000 and seen at the Angelman Syndrome Clinic at Massachusetts General Hospital to assess neurological, sleep, behavioral, gastrointestinal, orthopedic, and ophthalmologic functioning. The average age of this cohort was 24 years. Active seizures were present in 35%, nonepileptic myoclonus in 42%, and clinically significant tremors in 55%. Anxiety was present in 57%, increasing to 71% in those ages 26-43 years. In terms of sleep, 56% reported 8 hr of sleep or more, although 43% reported frequent nocturnal awakenings. Gastrointestinal issues remain problematic with 81% having constipation and 53% gastroesophageal reflux. The majority lived in a parent's home and remained independently mobile, though scoliosis was reportedly present in 30%, and 20% had reported low bone density/osteoporosis. The results of this study suggest that the prevalence of active seizures may decrease in adulthood but that the prevalence of movement disorders such as tremor and nonepileptic myoclonus may increase. Anxiety increases significantly as individuals age while defiant behaviors appear to decrease. Sleep dysfunction typically improves as compared to childhood but remains a significant issue for many adults. Other areas that require monitoring into adulthood include gastrointestinal dysfunction, and orthopedic/mobility issues, such as reported scoliosis and bone density, and ophthalmologic disorders.

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“…Far less is known is about the course of the syndrome in adulthood. Only a limited number of studies described the course of the AS in adults (Buckley, Dinno, & Weber, 1998;Clayton-Smith, 1993;Giroud et al, 2015;Guerrini et al, 1996;Jacobsen et al, 1998;L. A. E. M. Laan, Den Boer, Hennekam, Renier, & Brouwer, 1996;Leitner & Smith, 1996;Minassian et al, 1998;Moncla et al, 1999;Penner, Johnston, Faircloth, Irish, & Williams, 1993;Sandanam et al, 1997;Williams & Frias, 1982;Williams, Gray, Hendrickson, Stone, & Cantu, 1989).…”

mentioning

confidence: 99%

Clinical aspects of a large group of adults with Angelman syndrome

Besten

Jong

Geerts-Haages

et al. 2020

American J of Med Genetics Pt A

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Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe the evolution of the clinical phenotypes of AS in adulthood, using clinical data from 95 individuals (mean age 31.6 years, median 29.0 years, range 18–83 years), with genetically confirmed AS. Data was collected through physical examination and inspection of medical records, combined with questionnaires and interviews. Adults with AS experience substantial debilitating health problems. Constipation, reflux, visual problems, scoliosis, behavioral and sleeping problems occurred frequently and require appropriate attention. Epilepsy was reported in 57% of adults, negatively affecting the level of functioning. Non‐convulsive status epilepticus was not observed in the adults, however some individuals developed prolonged episodes of rhythmic shaking while awake. A decline in mobility was noted in the majority of adults. A minority of adults with AS showed microcephaly. Taken together, this first phenotypic study of adults with AS to include in person interviews with care‐givers and physical examination of patients, including the eldest adult reported to date, provides important insight in the development of the syndrome into adulthood. This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group.

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Angelman Syndrome: A Case Series Assessing Neurological Issues in Adulthood

Cited by 12 publications

References 25 publications

Epilepsy in Angelman syndrome: A scoping review

Epilepsy in Angelman syndrome: A scoping review

Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases

Clinical aspects of a large group of adults with Angelman syndrome

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