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Título

SNIJDERS BLOK FISHER SYNDROME: A CASE REPORT

Apresentação do caso único

An 8-year-old male patient, the son of non-consanguineous parents, was referred to the pediatric neurology outpatient clinic due to language delay and school difficulties, already being monitored by genetics. There were no noteworthy abnormalities in the gestational and perinatal history.

He exhibited language development delay and intellectual disability (IQ: 47) without impairments in social interaction or delays in other developmental milestones. Physical examination revealed dysmorphisms: elongated face, large and prominent ears, bilateral epicanthus, short upper eyelid fissure, anteverted nostrils, wide and smooth philtrum, small teeth, small hands and feet, hypoplasia of the fifth toenail, and partial syndactyly of the third and fourth toes.

A diagnostic investigation was conducted, including G-banded karyotyping, Fragile X testing, inborn error of metabolism screening, CGH array, brain MRI, audiometry, fundus examination, and echocardiogram, all with normal results.

At the age of 10, the first exome sequencing revealed a heterozygous mutation in the AHCY gene, which is associated with hypermethioninemia, an autosomal recessive inherited disease. At the age of 13, a new exome sequencing identified a variant of uncertain clinical significance (VUS) in the POU3F3 gene, associated with Snijders Blok Fisher Syndrome (OMIM: 618604), an autosomal dominant inherited disorder. Since the patient exhibited clinical features consistent with this syndrome, the diagnosis was confirmed.

Discussão

Snijders Blok Fisher Syndrome, recently described by Snijders et al. in 2019, is a rare autosomal dominant disorder caused by usually de novo heterozygous mutations in the POU3F3 gene located on chromosome 2q12. Patients with this syndrome present with global developmental delay, intellectual disability, speech and language acquisition delay, hypotonia, epilepsy, autistic behaviors, and various dysmorphisms. Brain MRI may revel abnormalities such as myelination changes, cerebral atrophy, corpus callosum malformation

Comentários finais

Due to its recent description, many patients with characteristics suggestive of this syndrome remain undiagnosed. Accurate diagnosis helps us better understand the patient's symptomatology, even if their treatment does not change. Furthermore, it provides answers to family concerns. New genetic diseases are discovered every day. Therefore, in cases where a genetic diagnosis cannot be made initially, it may be necessary to reanalyze genetic tests after some time.

Referências

Snijders Blok, L. S., Kleefstra, T., Venselaar, H., Maas, S., Kroes, H. Y., Lachmeijer, A. M. A., van Gassen, K. L. I., Firth, H. V., Tomkins, S., Bodek, S., DDD Study, Ounap, K., and 27 others. De novo variants disturbing the transactivation capacity of POU3F3 cause a characteristic neurodevelopmental disorder. Am. J. Hum. Genet. 105: 403-412, 2019.

Torun, D., Arslan, M., & Yüksel, Z. (2021). Coexistence of severe developmental delay, epilepsy, and hemangioma in Snijders Blok‐Fisher syndrome suggests the presence of a POU3F3 ‐related SNIBFIS endophenotype: A case report. American Journal of Medical Genetics Part A, 185(5), 1554–1560. doi:10.1002/ajmg.a.62135

Palavras Chave

Snijders Blok Fisher Syndrome; intellectual disability; POU3F3 gene