Dados do Trabalho

Título

MYOCLONIC-CHOREA IN PURA SYNDROME

Apresentação do caso

A 5-year-old female with a history of neurodevelopmental delay, hypersomnolence, seizures, and feeding disturbance, presented a complex movement disorder. Clinically, there was abnormal facial features, hypotonia, and the patient presented a mixed hyperkinetic movement disorder, consisting of chorea, dystonia, myoclonus, and hand stereotypies. The presence of generalized myoclonus, interposed with those hyperkinetic movements, resembled a “stop-motion” animation (Video 1), similar to the animation technique, in which objects are photographed frames by frame. Brain MRI showed mild frontal cortical atrophy (Figure 1). Genetic investigation was carried out, and CGH-array was performed, finding a pathogenic variant in PURA gene, compatible with PURA Syndrome [1].

Discussão

PURA gene encodes encodes a single-exon transcript that results in a 322 amino acids protein, namely Pur-α, a protein with regulatory functions in gene transcription, DNA replication, RNA transport and mRNA translation. PURA is essential for normal brain development, synapse formation and proliferation of neurons, astrocytes and oligodendrocytes in the central nervous system. PURA-NDDs have recently been identified and still may be underestimated. PURA Syndrome is characterized by neonatal hypotonia, significant neurodevelopmental delay with absence of speech, epileptic seizures, abnormal non-epileptic movements, and lack of independent ambulation in most of the patients. Also, is present in variable frequency: feeding difficulties, ophthalmological disorders, hypersomnolence, hypothermia and central apnea, urogenital malformations, skeletal abnormalities, and congenital heart defects. Since the initial description, 97 different pathogenic variants have been reported, but no clear genotype-phenotype correlations have emerged so far. The presence of myoclonic-chorea syndrome may be a clue to the final diagnosis.

Comentários finais

Complex hyperkinetic movement disorders in infants with global developmental delay may be an important clue to diagnose Pura Syndrome, being of clinical relevance, since affected patients may be misdiagnosed with dyskinetic cerebral palsy.

Referências (se houver)

1. Johannesen KM, Gardella E, Gjerulfsen CE, et al. PURA-Related Developmental and Epileptic Encephalopathy: Phenotypic and Genotypic Spectrum. Neurol Genet. 2021 Nov 15;7(6):e613. doi: 10.1212/NXG.0000000000000613.
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3. Reijnders MRF, Janowski R, Alvi M, Self JE, Van Essen TJ, Vreeburg M, et al. PURA syndrome: Clinical delineation and genotype-phenotype study in 32 individuals with review of published literature. J Med Genet. 2018;55(2):104–13.
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6. Trau SP, Pizoli CE. PURA Syndrome and Myotonia. Pediatr Neurol 2020;104:62–3. DOI: 10.1016/j.pediatrneurol.2019.09.008
7. Lalani SR, Zhang J, Schaaf CP, Brown CW, Magoulas P, Tsai ACH, et al. Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome. Am J Hum Genet 2014;95(5):579–83. DOI: http://dx.doi.org/10.1016/j.ajhg.2014.09.014
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Declaração de conflito de interesses de TODOS os autores

Autores declaram não ter conflito de interesses.