RESUMO
In 2017, Mattiolli et al. and Yan et al. described a series of patients with clinical findings essentially characterized by intellectual disabilities, ptosis, hypotonia, epilepsy, and weakness. They also found in these patients distinct heterozygous mutations in the BRPF1 gene, which plays a role in epigenetic regulation by promoting histone acetylation. The disease is known as Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP, OMIM #617333). Later, another 20 patients were also described by distinct reports, suggesting IDDDFP could be a more frequent cause of intellectual disability as it was thought before. Here, we describe a patient with normal intellectual development who had congenital ptosis, hypotonia, muscular weakness, atlanto-axial malformation, and pyramidal at the neurological examination. The patient has a rare nonsense variant on exon 3 of BRPF1 gene. We also describe a phenotypic amplification for conditions related to deficiency in histone modifications.
Assuntos
Blefaroptose , Deficiência Intelectual , Proteínas Adaptadoras de Transdução de Sinal/genética , Blefaroptose/diagnóstico , Blefaroptose/genética , Proteínas de Ligação a DNA/genética , Epigênese Genética , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Hipotonia Muscular/genética , Mutação , SíndromeRESUMO
INTRODUÇÃO: A síndrome de Wolf-Hirschhorn (SWH) é uma anomalia genética caracterizada pela deleção terminal do braço curto do cromossomo 4(4p16.3), cursando com deficiência mental e crises convulsivas. O estudo genético é fundamental para a correta caracterização sindrômica, diagnóstico e avaliação prognóstica. RELATO DE CASO: masculino, três anos, diagnosticado com SWH por meio de cariótipo, apresenta perímetro cefálico reduzido, baixa implantação de orelhas, macroglossia, epicanto, hipertelorismo e hipoplasia de gônadas. DISCUSSÃO: Dentre as manifestações clínicas, o hipertelorismo, epicanto e microcefalia são as mais expressivas, e o diagnóstico só é endossado por meio do cariótipo, permitindo-se assim realizar um seguimento mais dirigido. CONCLUSÃO: A SWH refere-se a uma doença genética rara, com prognóstico reservado e que necessita de diagnóstico precoce, a fim de permitir delinear um plano terapêutico estratégico, alcançando desse modo, um seguimento mais dirigido e uma melhor qualidade de vida ao doente e seus familiares
Introduction: Wolf-Hirschhorn syndrome is a genetic anomaly characterized by the terminal deletion of the short arm of chromosome 4 (4p16.3). Patients with this syndrome may present mental deficiency and seizures. The genetic study is fundamental for the syndromic diagnosis and prognosis evaluation. Case report: male, 3 years old, diagnosed with WHS (confirmed by karyotype), presents with reduced cephalic perimeter, low ear-implantation, macroglossy, epicanthus, hyperthelorism and gonadal hypoplasia. Discussion: Hypertelorism, epicanthus and microcephaly are the most significant clinical manifestations, and the diagnosis can only be confirmed using the karyotype, allowing the physician to establish a directed and more specific follow-up. Conclusion: WHS is a rare genetic disease with a dark prognosis and demands an early diagnosis, in order to allow the creation of a strategic therapeutic plan, suitable follow-up and a great improvement on the patient and family's quality of life