1- Serviço de Genética Médica, CHLC
2- Centro Hospitalar Universitário do Algarve, E.P.E.
- 21ª Reunião da Sociedade Portuguesa de Genética Humana. Apresentação sob a forma de poster.
Introdução: Multisystemic diseases represent a challenge to interpret clinical findings and complex genomic test results. A thorough family evaluation provides valuable clues and assumes a major role in the clinical practice of a Medical Genetics Centre. Sometimes these clues are crucial to achieve a definite diagnosis in multisystemic diseases with high phenotypic variability.
Métodos: We report a case of a 3 years-old girl referred to our Genetics Department due to a cardiopathy, cleft palate, microretrognathism, scoliosis, and minor dysmorphic features. Her father was healthy and her mother was obese and presented with lower limb lymphedema with onset in adolescence. A more subtle evaluation of the mother allowed us to identify a double row of lashes in the upper eyelids, suggesting the diagnosis of lymphedema - distichiasis.
Resultados: We performed Sanger sequencing of FOXC2 gene in mother’s DNA sample which revealed the presence of a heterozygous pathogenic variant c.1024del (p.Ala342Profd*28), confirming the clinical diagnosis. The proband had the same point mutation.
Conclusões: Although the classical presentation of lymphedema - distichiasis is characterized by lower limb lymphedema with onset at adolescence and the presence of anomalies of the eyelids, there are rarer presentations that include congenital cardiopathy (7%), cleft palate (4%) and scoliosis. Next Generation Sequencing with its ability to sequence many genes in less time has been progressively shifting Genetics paradigm and the concept of reverse phenotype is now deep-seated in the Medical Genetic field. Despite that and although the main features of a genetic disease are of major importance to ease the diagnostic clinical workflow, basic medical genetics terminology regarding phenotypic variability shouldn’t be forgotten especially when dealing with polymalformative diseases. This case illustrates the importance of a careful family and physical evaluation in the era of NGS.
Palavras Chave: lymphedema – distichiasis; FOXC2 gene