18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

The patient was the third child of healthy non-consanguineous parents. Her mother presented only with gestational diabetes during an otherwise uneventful pregnancy. Ultrasound at 19 weeks revealed severe hydrocephalus and the corpus callosum was not identified. Further fetal MRI at 27 weeks evidenced cerebral ventriculomegaly, enlargement of the 3rd ventricle, agenesis of the corpus callosum, communication between the 4th ventricle and great cistern, vermian and brainstem hypoplasia. A female infant was born full term, born in a cesarean birth due to non-reassuring fetal status. Her weight was normal for gestational age and she presented with macrocephaly with global hypotonia. The left cochlear-palpebral reflex was absent and funduscopic examination revelead bilateral optic nerve hypoplasia. Neonatal brain MRI confirmed fetal findings and also showed cerebellar hemispheres hypoplasia. During the following months she developed epilepsy, limbs spasticity and global development delay. Due to these findings, and exome was performed and revealed TUBA1A: c.185T>G, a likely pathogenic missense variant in heterozygosity.


Tubulin genes encode tubulin proteins which form heterodimers as fundamental components of microtubules and participate in substantial cellular processes of intracellular transport, cell division, neuronal migration, organization and differentiation and axon guidance and maintenance. Pathogenic variants in these genes are responsible for a complex and wide spectrum of cerebral malformations defined as tubulinopathies. To date, TUBA1A represents the main tubulinopathy gene. Main clinical features include global developmental delay, ophtalmological alterations, including optic nerve hypoplasia, epilepsy and spasticity.
The most common fetal imaging findings are cerebral ventriculomegaly and cerebellar hypoplasia and postnatal features includes alterations in cortical gyration, abnormalities in basal ganglia, corpus callosum or capsula interna and also cerebellar vermis and brainstem hypoplasia. Ventricular dilatation are reported in all cases in literatures.

Comentários finais

We present a rare case of tubulinopathy fetal MRI due to a novel variant in TUBA1A gene. The presence of fetal ventriculomegaly with cerebellar abnormalities should warrant a clue for evaluating tubulinopathies. Early diagnosis may assist in care coordination for the patient and further genetic counseling.

Referências (se houver)

1. ROMANIELLO, Romina; ZUCCA, Claudio; ARRIGONI, Filippo; BONANNI, Paolo; PANZERI, Elena; BASSI, Maria T.; BORGATTI, Renato. Epilepsy in Tubulinopathy: personal series and literature review. Cells, [S.L.], v. 8, n. 7, p. 669, 2 jul. 2019. MDPI AG. http://dx.doi.org/10.3390/cells8070669.

2. HEBEBRAND, Moritz; HÜFFMEIER, Ulrike; TROLLMANN, Regina; HEHR, Ute; UEBE, Steffen; EKICI, Arif B.; KRAUS, Cornelia; KRUMBIEGEL, Mandy; REIS, André; THIEL, Christian T.. The mutational and phenotypic spectrum of TUBA1A-associated tubulinopathy. Orphanet Journal Of Rare Diseases, [S.L.], v. 14, n. 1, p. 1-13, 11 fev. 2019. Springer Science and Business Media LLC. http://dx.doi.org/10.1186/s13023-019-1020-x.

3. BRAR, Bobby K.; THOMPSON, Marisa Gilstrop; VORA, Neeta L.; GILMORE, Kelly; BLAKEMORE, Karin; MILLER, Kristen A.; GIORDANO, Jessica; DUFKE, Andreas; WONG, Beatrix; STOVER, Samantha. Prenatal phenotyping of fetal tubulinopathies: a multicenter retrospective case series. Prenatal Diagnosis, [S.L.], v. 42, n. 13, p. 1686-1693, 28 nov. 2022. Wiley. http://dx.doi.org/10.1002/pd.6269.

Palavras Chave

TUBA1A; tubulinopathy; pontocerebellar hypoplasia; ventriculomegaly; epilepsy

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Declaramos não haver conflito de interesses de todos os autores.




UNIFESP - São Paulo - Brasil


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