1 - Unidade de Genética Médica, Área de Pediatria Médica, Hospital Dona Estefânia, Centro Hospitalar e Universitário de Lisboa Central, Lisboa, Portugal
- Reunião internacional - European Society of Human Genetics Conference 2021, publicação sob a forma de resumo, comunicação em poster
Resumo:
Introduction: Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK, OMIM #617140) is a recently described multisystemic disorder caused by de novo heterozygous pathogenic variants in SON gene. ZTTK syndrome is characterized by developmental delay, poor overall growth, facial dysmorphisms and structural malformations (cleft palate, brain, eye, heart, kidney, and skeletal anomalies). To date, only 35 patients were reported. Here, we present a new case of ZTTK syndrome aiming to contribute to its clinical and mutational spectrum characterization.
Methods: Clinical data was collected from the patient’s medical record and compared with literature.
Results: A six‑year‑old boy was referred for syndromic developmental delay evaluation. He was the first child of a non-consanguineous couple. Previous medical history included congenital heart defect, cleft palate, hypermetropia and recurrent infections. Physical examination showed short stature and facial dysmorphisms including mild frontal bossing, midface retraction, low‑set‑ears, downslanting palpebral fissures, broad and depressed nasal bridge, full cheeks, short philtrum, small mouth and micrognatia. Abdominal, renal and central nervous system imaging excluded other structural anomalies. Microarray analysis detected a 59.17 kb microdeletion of chromosome region 21q22.1 encompassing SON gene (arr[hg19] 21q22.11 (34,892,568-34,951,737)x1).
Discussion: The patient’s phenotype was strinkingly similar to ZTTK syndrome. All previous cases were due to loss‑of‑function mutations in SON. Notably, our case was the first associated with a 21q22.1 microdeletion involving a whole SON gene deletion. Apparently, the co‑deleted genes (GART, MIR6501 and DONSON) did not contribute to the clinical phenotype.
Conclusion: This report confirms that ZTTK syndrome can be caused by 21q22.1 microdeletions, further broadening ZTTK mutational spectrum.
Palavras Chave: Zhu-Tokita-Takenouchi-Kim syndrome, SON gene, 21q22.11 microdeletion