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Título

"PURA SYNDROME": A CASE REPORT

Apresentação do caso único

This is the second daughter of a non-consanguineous couple, with no complications during the prenatal period, birth, or relevant family history. During the neonatal period, she began experiencing episodes of apnea, hypersomnolence, hypoactivity, initial central hypotonia, dysphagia, and hypothermia. In the first year of life, she was investigated for Prader-Willi syndrome, with negative results. She developed precocious puberty at 2 years (with rapid resolution), global developmental delay, failure to thrive, absence of speech, exaggerated startle response, dyskinesia, spasticity of the lower limbs, sat at 2 years, and achieved supported walking at 10 years, currently digitigrade. At 13 years old, she began experiencing epileptic seizures with behavioral arrest and dysautonomia. Complementary investigations revealed focal interictal activity on electroencephalogram and delayed myelination on neuroimaging. Molecular genetic testing with next-generation sequencing, using a panel for movement disorders and neurodevelopmental disorders, identified a probably pathogenic variant, c.572C>T (p.Pro191Leu) in heterozygous form, in the PURA gene (OMIM *600473).

Discussão

Pathogenic variants in heterozygous form in the PURA gene are associated with Neurodevelopmental Disorder with Neonatal Respiratory Failure, Hypotonia, and Feeding Difficulties (NEDRIHF, OMIM# 616158), known as "PURA Syndrome." It is characterized by significant neurodevelopmental delay, absence of speech, and lack of independent ambulation. Typical, frequent, and early-onset problems present in this case include hypotonia, hypothermia, somnolence, feeding difficulties, excessive hiccups, central apneas, movement disorders, and epilepsy. Half of the cases manifest seizures, and the patient is currently on monotherapy, with literature describing a potential progression to Lennox-Gastaut Syndrome. She also presents endocrine disorders (vitamin D deficiency and previous precocious puberty), which, along with congenital cardiac, urogenital, and skeletal malformations, are less common.

Comentários finais

Although global developmental delay is a common manifestation in pediatric neurology practice, the characterization and severity of the manifestations are crucial for seeking differential diagnoses and specific etiological diagnosis. Accurate diagnosis allows for individualized care and monitoring of potential comorbidities and complications.

Referências

Lalani SR, et al. Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome. Am J Hum Genet. 2014 Nov 6;95(5):579-83. PMID: 25439098.

Reijnders MRF, Janowski R, Alvi M, et alPURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literatureJournal of Medical Genetics 2018;55:104-113.

Reijnders MRF, Leventer RJ, Lee BH, et al. PURA-Related Neurodevelopmental Disorders. 2017 Apr 27. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK426063/

ONLINE MENDELIAN INHERITANCE IN MAN. PURA gene. OMIM, [s.d.]. Disponível em: https://www.omim.org/entry/600473. Acesso em: 14 ago. 2024.

ONLINE MENDELIAN INHERITANCE IN MAN. Neurodevelopmental Disorder with Neonatal Respiratory Failure, Hypotonia, and Feeding Difficulties (NEDRIHF). OMIM, [s.d.]. Disponível em: https://www.omim.org/entry/616158. Acesso em: 14 ago. 2024.

Palavras Chave

Hypotonia; Neurodevelopmental Delay; PURA syndrome