Angelman syndrome in Hong Kong Chinese: A 20 years’ experience

Luk, Ho Ming; Lo, Ivan F.M.

doi:10.1016/j.ejmg.2016.05.003

Cited by 33 publications

(44 citation statements)

References 30 publications

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“…This is the largest clinical cohort described thus far. Our data confirm the distribution of the genetic subtypes, the overall clinical presentation and the presence of a more severe phenotype in the 15q11.2‐q13 deletion subtype (Clayton‐Smith & Laan, ; Luk & Lo, ; Mertz et al, ; Shaaya, Grocott, Laing, & Thibert, ; Tan et al, ). Novel findings are a negative association of epilepsy and an earlier age at onset of epilepsy on development, a high occurrence of NCSE, crouch gait in the older children, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia in all genetic subtypes.…”

Section: Discussionsupporting

confidence: 84%

“…Overall, the distribution of the underlying genetic causes in our AS cohort is comparable to AS cohorts as reported for the United States, Denmark, and Hong Kong, with chromosomal 15q11.2‐q13 deletion being the most common cause and an IC abnormality showing the lowest prevalence (Clayton‐Smith & Laan, ; Luk & Lo, ; Mertz et al, ; Shaaya et al, ; Tan et al, ). In our cohort, the mean age of diagnosis was significantly earlier in children with a deletion than in children with a nondeletion, similar to other cohorts (Mertz et al, ; Tan et al, ).…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Heus

Mous

Hooven‐Radstaake

et al. 2019

American J of Med Genetics Pt A

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This study presents a broad overview of health issues and psychomotor development of 100 children with Angelman syndrome (AS), seen at the ENCORE Expertise Center for AS in Rotterdam, the Netherlands. We aimed to further delineate the phenotype of AS, to evaluate the association of the phenotype with genotype and other determinants such as epilepsy and to get insight in possible targets for intervention. We confirmed the presence of a more severe phenotype in the 15q11.2-q13 deletion subtype. Novel findings were an association of (early onset of) epilepsy with a negative effect on development, a high occurrence of nonconvulsive status epilepticus, a high rate of crouch gait in the older children with risk of deterioration of mobility, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia across all genetic subtypes. Natural history data are needed to design future trials. With this large clinical cohort with structured prospective and multidisciplinary follow-up, we provide unbiased data on AS to support further intervention studies to optimize outcome and quality of life of children with AS and their family. K E Y W O R D S development, epilepsy, genotype-phenotype, growth, UBE3A

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 80%

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Heus

Mous

Hooven‐Radstaake

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

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“…In contrast, those with unparental disomy, an imprinting defect or mosaic AS tend to have a milder phenotype. These variable AS phenotypes are summarized in Table [Varela et al, ; Tan et al, ; Horváth et al, ; Bai et al, , Luk and Lo, ]. Importantly, the phenotype of individuals with mosaic AS may not be entirely consistent with the diagnostic features recommended by the 2005 Consensus Statement of the United States AS Foundation [Williams et al, ].…”

Section: Discussionmentioning

confidence: 99%

Atypical Angelman syndrome due to a mosaic imprinting defect: Case reports and review of the literature

Fevre

Beygo

Silveira

et al. 2017

American J of Med Genetics Pt A

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Angelman syndrome (AS) is characterized by severe intellectual disability, limited, or absent speech and a generally happy demeanor. The four known etiological mechanisms; deletions, uniparental disomy, imprinting defects, and UBE3A mutation all affect expression of the UBE3A gene at 15q11-q13. An atypical phenotype is seen in individuals who are mosaic for a chromosome 15q11-q13 imprinting defect on the maternal allele. These patients present with a milder phenotype, often with hyperphagia and obesity or non-specific intellectual disability. Unlike typical AS syndrome, they can have a vocabulary up to 100 words and speak in sentences. Ataxia and seizures may not be present, and the majority of individuals do not have microcephaly. Here we review the current literature and present three individuals with atypical AS caused by a mosaic imprinting defect to demonstrate why DNA methylation analysis at the SNRPN locus needs to be considered in a broader clinical context. © 2017 Wiley Periodicals, Inc.

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“…Angelman syndrome (AS) is a rare neurodevelopmental disorder with recent estimates of its prevalence being between 1:22,000 and 1:52,000 [Oiglane‐Shlik et al, ; Mertz et al, ; Luk and Lo, ], although previous studies had suggested that the prevalence was about 1 in 10,000 to 1 in 20,000 [Kyllerman, ; Petersen et al, ; Buckley et al, ]. Individuals with AS have global developmental delay that evolves to severe intellectual disability, with their language skills being more delayed than their motor skills, and their expressive language being far more delayed than their receptive language, usually having only minimal speech.…”

Section: Introductionmentioning

confidence: 99%

Angelman syndrome: Current and emerging therapies in 2016

Tan¹,

Bird²

2016

American J of Med Genetics Pt C

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Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by a loss of the maternally-inherited UBE3A; the paternal UBE3A is silenced in neurons by a mechanism involving an antisense transcript (UBE3A-AS) at the unmethylated paternal locus. We reviewed all published information on the clinical trials that have been completed as well as the publicly available information on ongoing trials of therapies in AS. To date, all clinical trials that strove to improve neurodevelopment in AS have been unsuccessful. Attempts at hypermethylating the maternal locus through dietary compounds were ineffective. The results of an 8-week open-label trial using minocycline as a matrix metalloproteinase-9 inhibitor were inconclusive, while a subsequent randomized placebo-controlled trial suggested that treatment with minocycline for 8 weeks did not result in any neurodevelopmental gains. A 1-year randomized placebo-controlled trial using levodopa to alter the phosphorylation of calcium/calmodulin-dependent kinase II did not lead to any improvement in neurodevelopment. Topoisomerase inhibitors and antisense oligonucleotides are being developed to directly inhibit UBE3A-AS. Artificial transcription factors are being developed to "super activate" UBE3A or inhibit UBE3A-AS. Other strategies targeting specific pathways are briefly discussed. We also reviewed the medications that are currently used to treat seizures and sleep disturbances, which are two of the more common complications of AS. © 2016 Wiley Periodicals, Inc.

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Angelman syndrome in Hong Kong Chinese: A 20 years’ experience

Cited by 33 publications

References 30 publications

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

An overview of health issues and development in a large clinical cohort of children with Angelman syndrome

Atypical Angelman syndrome due to a mosaic imprinting defect: Case reports and review of the literature

Angelman syndrome: Current and emerging therapies in 2016

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