1 - Serviço Genética Médica, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portuga
- European Human Genetics Conference (Poster)
Introduction: Terminal 13q34 microdeletions are rare chromosomal anomalies, associated with developmental delay (DD), intellectual disability (ID), autism, epilepsy and dysmorphisms. CHAMP1 gene (OMIM* 616327), located within the 13q34 deleted region, encodes for a zinc finger phosphoprotein, crucial to chromosome segregation via attachment of kinetochore-microtubule. Loss-of-function pathogenic variants in CHAMP1 result in a neurodevelopmental disorder characterised by DD, severe ID, speech and language impairment, autism and sleep disturbances, hypotonia, microcephaly, seizures, ophthalmologic issues and gastrointestinal problems. It is hypothesised that CHAMP1 haploinsufficiency can also be associated with the described phenotype but with a milder presentation.
Case presentation: A 15-year-old boy was first observed in our Genetics Clinic due to ID, autism with absent speech, epilepsy, axial hypotonia and sleep disturbance. At observation, our patient presented with dysmorphic facial features, tall stature and scoliosis. Brain MRI, electrocardiogram and FRAXA study were normal. Microarray analysis identified a 45.6 Kb heterozygous deletion involving 13q34 chromosome region, classified as variant of unknown significance. Parental testing revealed that 13q34 microdeletion was de novo.
Conclusions: To the best of our knowledge, this is the smallest 13q34 microdeletion reported to date, encompassing only one morbid OMIM gene (CHAMP1), associated with ID, autism, epilepsy and sleep disturbances. We believe that our case provides evidence that CHAMP1 haploinsufficiency may contribute to the presented neurodevelopment phenotype, providing a possible genotype-phenotype correlation. Given the rarity of this microdeletion, further evidence is needed to enhance our understanding of the etiology of this condition, contributing to improve diagnosis and provide genetic counselling for these patients.
Palavras Chave: Dysmorphism, genotype-phenotype correlation, haploinsufficiency, microdeletion, nerodevelopmental disorder.