Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability

Okamoto, Nobuhiko; Miya, Fuyuki; Kitai, Yukihiro; Tsunoda, Tatsuhiko; Kato, Mitsuhiro; Saitoh, Shinji; Kanemura, Yonehiro; Kosaki, Kenjiro

doi:10.1007/s10072-021-05152-y

Cited by 6 publications

(21 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Resembling our report, none of the parents of the affected individuals from these three families exhibited movement disorders. Brain MRI shows no evidence of structural abnormalities in ADCY5 dyskinesia, 6 however, similar to the report by Okamoto et al, 4 we found mild structural brain abnormality including corpus callosum hypoplasia in one of the siblings. These MRI findings would need to be validated in further families with an AR form of ADCY5‐ related dyskinesia.…”

supporting

confidence: 90%

“…To date, from over 70 ADCY5 ‐related disease reports, only three have been associated with an autosomal recessive (AR) inheritance, while the rest of the reports were linked to an autosomal dominant (AD) inheritance. 1 , 2 , 3 , 4 Clinical comparison of the cases with different modes of inheritance in ADCY5‐ related disease is currently challenging due to the paucity of reports on the AR form and broad phenotype of the AD form. Herein, we report a family with an AR ADCY5‐ related disease.…”

mentioning

confidence: 99%

“…Mild brain stem hypoplasia was present in one of these siblings. 4 (Tables S1 and S2 ). All cases with the myoclonus‐dystonia phenotype, with the age range of 6–27 years old (eight affected individuals), had attained independent ambulation before the age of 2 years despite the reported developmental delay.…”

mentioning

confidence: 99%

See 2 more Smart Citations

A Novel Homozygous ADCY5 Variant is Associated with a Neurodevelopmental Disorder and Movement Abnormalities

Kaiyrzhanov

Zaki

Maroofian

et al. 2021

Movement Disord Clin Pract

View full text Add to dashboard Cite

supporting

confidence: 90%

mentioning

confidence: 99%

See 1 more Smart Citation

A Novel Homozygous ADCY5 Variant is Associated with a Neurodevelopmental Disorder and Movement Abnormalities

Kaiyrzhanov

Zaki

Maroofian

et al. 2021

Movement Disord Clin Pract

View full text Add to dashboard Cite

“…For example, a missense mutation (A726T) has been associated with familial dyskinesia with facial myokymia (FDFM) [ 92 ]. In addition, a homozygous missense or heterozygous de novo mutation (p.R418W) results in early onset of motor disability and movement disorder with severe intellectual disability [ 93 – 95 ].…”

Section: Expression and Functions Of Adcys In The Cnsmentioning

confidence: 99%

Expression and functions of adenylyl cyclases in the CNS

Devasani

Yao

2022

Fluids Barriers CNS

View full text Add to dashboard Cite

Adenylyl cyclases (ADCYs), by generating second messenger cAMP, play important roles in various cellular processes. Their expression, regulation and functions in the CNS, however, remain largely unknown. In this review, we first introduce the classification and structure of ADCYs, followed by a discussion of the regulation of mammalian ADCYs (ADCY1-10). Next, the expression and function of each mammalian ADCY isoform are summarized in a region/cell-specific manner. Furthermore, the effects of GPCR-ADCY signaling on blood–brain barrier (BBB) integrity are reviewed. Last, current challenges and future directions are discussed. We aim to provide a succinct review on ADCYs to foster new research in the future.

show abstract

“…2,3 The disease may be caused by monallelic variants (autosomal dominant) or more rarely biallelic variants (autosomal recessive). [3][4][5][6][7][8][9] The levels of cyclic AMP (cAMP) in the striatum is involved in the fine regulation of movement execution, modulating facilitatory and inhibitory outputs. 10 Alteration of the striatal cAMP turnover is involved in many hyperkinetic movement disorders such as levodopa-induced dyskinesia, chorea in Huntington's disease, and hyperkinetic movements associated with mutations in GNAO1, GNAL, GNB1, PDE10A or PDE2A.…”

mentioning

confidence: 99%

Scoping Review onADCY5‐Related Movement Disorders

Menon,

Nilles,

Silveira‐Moriyama

et al. 2023

Movement Disord Clin Pract

View full text Add to dashboard Cite

Background Adenylyl cyclase 5 (ADCY5)‐related movement disorder (ADCY5‐RMD) is a rare, childhood‐onset disease resulting from pathogenic variants in the ADCY5 gene. The clinical features, diagnostic options, natural history, and treatments for this disease are poorly characterized and have never been established through a structured approach. Objective This scoping review attempts to summarize all available clinical literature on ADCY5‐RMD. Methods Eighty‐seven articles were selected for inclusion in this scoping review. The majority of articles identified were case reports or case series. Results These articles demonstrate that patients with ADCY5‐RMD suffer from permanent and/ or paroxysmal hyperkinetic movements. The paroxysmal episodes can be worsened by environmental triggers, in particular the sleep–wake transition phase in the early morning. Occurrence of nocturnal paroxysmal dyskinesias and perioral twitches are highly suggestive of the diagnosis when present. In the majority of patients intellectual capacity is preserved. ADCY5‐RMD is considered a non‐progressive disorder, with inter‐individual variations in evolution with aging. Somatic mosaicism, mode of inheritance and the location of the mutation within the protein can influence phenotype. Conclusions The current evidence for therapeutic options for ADCY5‐RMD is limited: caffeine, benzodiazepines and deep brain stimulation have been consistently reported to be useful in case reports and case series.

show abstract

Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability

Cited by 6 publications

References 10 publications

A Novel Homozygous ADCY5 Variant is Associated with a Neurodevelopmental Disorder and Movement Abnormalities

A Novel Homozygous ADCY5 Variant is Associated with a Neurodevelopmental Disorder and Movement Abnormalities

Expression and functions of adenylyl cyclases in the CNS

Scoping Review onADCY5‐Related Movement Disorders

Contact Info

Product

Resources

About