Dados do Trabalho

Título

NEURODEVELOPMENTAL DELAY AND MOVEMENT DISORDER: A RARE PRESENTATION OF ADCY5 MOVEMENT RELATED DISORDER

Apresentação do caso único

7-year-old, female, only child of consanguineous parents, born term, without prenatal or perinatal complications. She began follow-up due to a global developmental delay since birth, she has never achieved any developmental milestones. Moreover, she had choreoathetoic movements of the upper limbs. On physical examination, in addition to choreatotic movements, she presented appendicular spastic pyramidal syndrome and axial hypotonia without involvement of cranial nerves. No dysmorphic signs were evident. In the investigation, she performed magnetic resonance imaging and screening for inborn errors of metabolism, which were normal. Furthermore, the electroencephalogram did not show a electroclinical correlation between the observed movements and epileptiform waves. As a treatment, with the use of benzodiazepines, the distal movement became less evident. Due to the hypothesis of a genetic syndrome associated with neurotransmitter disorders and given the availability of the test, a genomic evaluation was done, which revealed a probably pathogenic homozygous mutation in the ADCY5 gene(c1762G>T, pD588N). Unfortunately, the patient died due to complications from a respiratory infection.

Discussão

ADCY5 was first described as an autosomal dominant mutation in 2001.Classically, this disease has as a clinical characteristic a heterogeneous picture of chorea, myoclonia and dystonia, which mainly affects the facial muscles, periorbitary and perioral region, with the onset of manifestations in childhood or late adolescence. In most cases a stabilization of the movements occurs in the adult phase, and in some cases, less commonly, they appear in the slowly progressive form. Resonance and biochemical tests are typically normal.
In general, the autosomal dominant picture is due to function gains of adenylate cyclase, but over time new mutations with loss of function, and consequently with new phenotypes, have been seen. Since 2018, cases are being described, which, like that of our patient, derive from the autosomal recessive mutation of the gene. So far, there are 5 publications, with a report of 5 families affected. These patients have in common the loss of function of the C1 portion of the adenylate cyclose enzyme and a more severe phenotype.

Comentários finais

Autosomal recessive ADCY5 is a rare movement disorders with only 5 families described in the world so far. In Brazil, there are still no reports of recessive forms.

Referências

Bohlega SA, Abou-Al-Shaar H, AlDakheel A, Alajlan H, Bohlega BS, Meyer BF, et al. Autosomal recessive ADCY5-related dystonia and myoclonus: expanding the genetic spectrum of ADCY5-related move- ment disorders. Parkinsonism Relat Disord 2019;64(9513583):145–149.
Barrett MJ, Williams ES, Chambers C, Dhamija R. Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus. Neurol Genet 2017;3(5):193.
El-Hattab AW, Scaglia F. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria. 2009 May 26 [Updated 2023 Sep 28]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6803/
Kaiyrzhanov R, Zaki MS, Maroofian R, Dominik N, Rad A, Vona B, Houlden H. A novel homozygous ADCY5 variant is associated with a neurodevelopmental disorder and movement abnormalities. Mov Disord Clin Pract 2021;8(7):1140–1143.
Menon PJ, Nilles C, Silveira-Moriyama L, Yuan R, de Gusmao CM, Münchau A, Carecchio M, Grossman S, Grossman G, Méneret A, Roze E, Pringsheim T. Scoping Review on ADCY5-Related Movement Disorders. Mov Disord Clin Pract. 2023 Jun 6;10(7):1048-1059. doi: 10.1002/mdc3.13796. PMID: 37476318; PMCID: PMC10354615.
Okamoto N, Miya F, Kitai Y, et al. Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability. Neurol Sci 2021;42(7):2975–2978
Sagi-Dain L, Shemer L, Larom G, Adir V, Haddah-Halloun J, Peleg A. A first report of homozygous missense mutation in the ADCY5 gene related to an autosomal dominant Dyskynesia syndrome. Eur J Hum Genet 2019;27((Sagi-Dain L.; Shemer L.; Larom G.; Adir V.; Haddah- Halloun J.; Peleg A.) Carmel Medical Center, Haifa, Israel):1412

Palavras Chave

Developmental delays; Movement disorder; Rare Diseases