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Título

Miller-Dieker syndrom: a case-based update

RESUMO

CASE PRESENTATION: A 5-year-old female presents with significant delay in neuropsychomotor development, first observed at 3 months of age, and refractory epileptic seizures, despite multiple regimens with anti-seizure drugs. Previous physiological history revealed gestational bleeding until the 4th month of pregnancy. Neurological exam revealed adequate visual contact and social smile, but no language, and significant axial and appendicular hypotonia, with absence of cervical tone. Morphological examination revealed the presence of microcephaly, divergent strabismus to the right, epicanthus, ocular hypertelorism, flat nasal base, small and upturned nose, palpebral fissures turned down and prominent forehead. Computed Tomography and Magnetic Resonance Imaging of the skull were performed, which showed lissencephaly and agiria. A molecular study to search for microdeletion syndromes was performed, which detected deletions in the METTL16 and PAFAH1B1 genes of chromosome 17p13.3.
DISCUSSION: Miller-Dieker syndrome (MDS) is a rare genetic disease that occurs due to depletions in chromosome 17p13.3. It is characterized by lissencephaly, craniofacial alterations, growth retardation, delay in neuropsychomotor development and it is common to present refractory seizures. Lissencephaly associated with MDS tends to be more severe when compared to other diseases of chromosome 17p13.3, being classified as grade 1 lissencephaly (agiria), also distinguished by its craniofacial alterations. The genetic deletion of MDS usually occurs between the PAFAH1B1 and YWHAE genes, with the PAFAH1B1 isolated deletion resulting in classic lissencephaly. In this case, there was a deletion of two genes between these chromosomes, which configures a MDS case. There was also a deletion of METTL16 gene that succeeds the PAFAH1B1, and, despite being associated with the MDS, the exact effects on the progression or severity of the syndrome are not elucidated. It is known, however, that it may be associated with hepatocellular carcinoma.
FINAL COMMENTS: MDS is rare and has a poor prognosis, with a reduced life expectancy in most cases. Its suspicion is very important when there is a typical phenotype associated with refractory seizures, requiring evidence of lissencephaly by imaging.

Palavras Chave

Miller-Dieker syndrom, refractory seizures, lissencephaly

Área

Neurogenética