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Título

CASE REPORT OF A NEW VARIANT AND LITERATURE REVIEW OF FOXG1-RELATED SYNDROME: ATYPICAL RETT SYNDROME OR A DIFFERENT ENTITY?

Apresentação do caso

A 13-month-old boy was evaluated at our institution for developmental delay. He was born to non-consanguineous parents as the first child. Birth weight was 3360g, length was 49 cm and head circumference 32.5 cm. Developmental delay was noticed at 6 months of age. He started to sit without support at 10 months. He couldn't crawl and was non-verbal. He has exotropia of the left eye and chronic constipation. There is no history of regression, epilepsy or loss of social interaction. The family history is unremarkable. In his segment, head circumference stagnation was noticed at 43 cm and at 19 months the patient had dyskinesia. MRI with delayed myelination of frontal lobe and corpus callosum. A next generation sequencing (NGS) panel detect a new variant caused by a deletion on FOXG1: chr14:28.768.689 ACTGT>A.

Discussão

The first case of FOXG1 mutation was reported in 2005, with some other reports appearing later. These patients were initially described as having the congenital variant of Rett syndrome. Currently, these individuals are considered to belong to a distinct entity called “FOXG1-related encephalopathy”, mainly due to the lack of regression observed in Rett syndrome. Other symptoms of FOXG1 are lack of eye contact, ocular abnormalities, epilepsy, developmental delay, microcephaly, telencephalon malformations, gastrointestinal symptoms (reflux or constipation), dyskinesia, stereotypies (hand wringing is rare, unlike in Rett syndrome) and sleep disturbances. Our patient had severe microcephaly and developmental delay, but the other symptoms were much more subtle. This patient is progressively making developmental gains and doing well, this clearly exposes the differences between Rett syndrome and the FOXG1 gene. On the other hand, there are case reports of FOXG1 showing different clinical features for different types of mutations or for different sites of mutations. For example, FOXG1 duplications usually cause early epilepsy, whereas intragenic mutations cause late epilepsy after 2 or 3 years of age. In the reported case, the FOXG1 mutation is a deletion in the C-terminal region and is associated with milder phenotypes, which perhaps explains the few changes on MRI, the patient's mild clinical picture and the absence of epilepsy so far.

Comentários finais

This report seeks to describe a new genetic variant, expanding the description of FOXG1-related encephalopathy and reinforcing the tendency to define it as a specific disease.

Referências (se houver)

1. WONG, Lee-Chin. FOXG1-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms. International Journal of Molecular Sciences. August 2019
2. Jacob, F., Ramaswamy, V., Andersen, J. et al. Atypical Rett syndrome with selective FOXG1 deletion detected by comparative genomic hybridization: case report and review of literature. Eur J Hum Genet 17, 1577–1581 (2009).
3. Florian C, Bahi-Buisson N, Bienvenu T. FOXG1-Related Disorders: From Clinical Description to Molecular Genetics. Mol Syndromol. 2012 Apr;2(3-5):153-163.

Palavras Chave

FOXG1; Rett; developmental delay; microcephaly

Fonte de Fomento (se houver)

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Não há interesses;

Área

Neurogenética