Dados do Trabalho

Título

DEVELOPMENT DELAY, TREMOR AND OTHER HYPERKINETIC MOVEMENTS CAUSED BY 6P22 COPY NUMBER VARIATION MUTATION.

Apresentação dos casos

We present a case of a 39 year-old woman with a history of left upper limb tremor since the age of sixteen. Delivery and neonatal period were unremarkable, but she presented delay on walking and on speech abilities. She also was amaurotic in her right eye and needed special assistance during school due to difficulties in learning.
On physical examination, some morphologic alterations were seen, such as bilateral microphthalmia, micrognathia, ogival palate and low stature. Ophtalmological evaluation showed bilateral dystrophic microcornea, corectopy, pale papilla and retinal atrophy. On neurological examination, we found global hyperreflexia with bilateral Babinski and Hoffman signs, head and jaw as well as rest and action tremor on all four limbs. Tremor was irregular, simetric, with high frequency and low amplitude and was predominantly kinectic, proximal and on the lower limbs. She also presented bilateral mild bradkynesia and rigidity. No other neurological abnormalities were found.
Various symptomatic medications were tried without success. Regarding her family history, there is no consanguinity, her maternal grandfather had Parkinson’s disease and a paternal cousin showed orthopedic malformations. She has 7 siblings, all without known diseases. Brain MRI and laboratory work-up, including iron and copper metabolism, hormonal profile, serologic tests, renal, thyroid and hepatic function were unrevealing. CSF analysis showed only elevated proteins. Exome sequencing showed copy number variation (CNV) mutation in heterozygosity involving the 6p22.3-p22.1 region, classified as probably pathogenic.

Discussão

In the region where the CNV was found in heterozygosity, 125 genes are located, 10 of which (JARID2, HIST1H1E, RIPOR2, ATXN1, HIST1H4C, HIST1H4I, SLC17A3, GMNN, HIST1H4E, SOX4) have been described as having associations with clinical phenotypes and patterns of autosomal dominant inheritance. Although there is no evidence of triplosensitivity for any of these genes, the patient’s phenotypic characteristics may be linked to some of the described syndromes, suggesting potential pathogenic mechanisms not yet documented in the literature.

Comentários finais

We present a case of a CNV mutation involving the 6p22.3-p22.1 region with movement disorders and global development delay. To our knowledge this is the first case description with such mutation leading to this clinical phenotype.

Referências

https://www.omim.org/entry/184430?search=6p&highlight=6p
https://www.omim.org/entry/601556?search=6p&highlight=6p
https://www.omim.org/entry/607017?search=6p&highlight=6p
https://www.omim.org/entry/235200?search=6p&highlight=6p

Palavras Chave

parkinsonism; Neurogenetics; Developmental delays