1 - Unidade de Genética Médica, Área de Pediatria Médica, Hospital de Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
2 - Serviço de Genética Médica, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal
3 - Serviço de Genética Médica, Departamento de Pediatria, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, Lisboa, Portugal
4 - Departamento de Pediatria, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal
5 - Unidade de Neurologia Pediátrica, Departamento de Pediatria, Centro Hospitalar Universitário de São João, Porto, Portugal
6 - Serviço de Genética Médica, Hospital Pediátrico de Coimbra, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
- Reunião nacional - 24.ª Reunião Anual da Sociedade Portuguesa de Genética Médica, publicação sob a forma de resumo, comunicação oral
Resumo:
Introduction: Mandibulofacial dysostosis type Guion-Almeida (MFDGA, OMIM#610536) is an autosomal dominant condition caused by haploinsufficiency of EFTUD2 gene, which encodes a component of the major spliceosome that removes introns from pre-mRNA transcripts. Clinically, MFDGA presents with malar and mandibular hypoplasia as the core phenotype, associated with microcephaly, developmental delay/intellectual disability (DD/ID), and structural congenital anomalies. Its highly variable manifestations makes MFDGA an underdiagnosed disorder and frequently misdiagnosed with CHARGE syndrome, oculoauriculovertebral spectrum, and other mandibulofacial dysostosis.
Aim: Here, we present a national case series of patients diagnosed with MFDGA.
Methods: Retrospective review of clinical and molecular data from MFDGA patients diagnosed in Portuguese Clinical Genetics Departments.
Results: We identified 7 patients (5 males, 2 females) from 7 families. All patients had mandibular hypoplasia, DD/DI and microcephaly. The most common facial dysmorphisms were micro/retrognatia (6/7), ear anomalies (5/7), prominent nose (3/7), and facial asymmetry (3/7). The most common structural anomalies were airway abnormalities [esophageal atresia (4/7), choanal atresia/stenosis (2/7), and velopharyngeal insufficiency (1/7)], followed by heart defects (3/7), and genitalia anomalies (1/6). Additional relevant phenotypic features were growth delay/short stature (5/7), feeding difficulties (3/7), and vision problems (3/7). Pregnancy complications were reported in 3 cases. 4 out of 7 patients required invasive interventions. Regarding the diagnostic approach, other specific genetic diagnosis, namely CHARGE and Dubowitz syndromes, were first considered in 2 cases, while MFDGA was the first diagnostic hypothesis in 1 case. A total of 7 different EFTUD2 sequence variants were identified: 4 frameshift [pathogenic (P)/likely pathogenic (LP)]; 2 affecting splicing [2 (P/LP)]; and 1 stop gain (LP).
Conclusions: Our data is consistent with the literature. Also, this study adds information to the clinical level – expandes phenotypic spectrum - and molecular profile – 7 novel EFTUD2 variants are reported.
Palavras Chave: Mandibulofacial dysostosis type Guion-Almeida, EFTUD2 gene, national case series