Akademik Veri Yönetim Sistemi
EuroDysmorpho 2024, Ljubljana, Slovenya, 18 Eylül 2024, ss.61-62, (Tam Metin Bildiri)
17:00 ADDING PIECES TO THE PUZZLE: SUBTLE DYSMORPHIC TRAITS IN ASSOCIATION WITH A NOVEL NCKAP1 VARIANT
Ozge Beyza Gundogdu Ogutlu1, Berrin Demir2, Zeynep Utlu3, Merve Karabak4, Oguzhan Yaralı1
1Erzurum City Hospital, Department of Medical Genetics, Erzurum, Turkiye
2Department of Radiology, Erzurum City Hospital, Erzurum, Turkiye
3Atatürk University, Department of Skin and Venereal Diseases, Erzurum, Turkiye
4Erzurum City Hospital, Department of child and adolescent psychiatry, Erzurum, Turkiye
Background: The NCKAP1 gene's association with neurodevelopmental disorders (NDDs) presenting with autism spectrum disorder (ASD) traits is understudied, with no related disorder cataloged in the OMIM database. We present a pediatric case exhibiting a spectrum of NDD features and subtle dysmorphic traits associated with a novel de novo NCKAP1 variant, underscoring the importance of documenting such features to enrich phenotypic profiling (1).
Case Presentation: The infant, born at 27 weeks of gestation, faced significant initial challenges requiring intensive neonatal care. Developmental trajectories were marked by speech regression and motor delays, with seizure onset at three months. Remarkably, the patient demonstrated speech recovery following a seizure-free interval. Behavioral evaluation noted patterns of self-harm, social disengagement, and disrupted sleep. Notably, the patient displayed subtle dysmorphic features, including microcephaly, a posteriorly positioned hairline, broad eyebrow ridge, sparse eyebrows, a prominent forehead, and fusiform fingers, enriching the phenotype spectrum for NCKAP1-related disorders.
Genetic Findings: Genetic testing revealed a NCKAP1 (NM_013436.5) c.2021+1G>A de novo variant within the NCKAP1 gene, contributing to the limited pool of known cases. This variant adds to the understanding of the gene’s impact on neurodevelopment, particularly as it relates to nuanced dysmorphic presentations.
Conclusions: Although subtle, the dysmorphic features in this case of an NCKAP1 variant contribute valuable information to the phenotype spectrum, suggesting a broader clinical presentation than currently recognized. This case emphasizes the importance of nuanced phenotypic descriptions in genetic disorders with few reported cases, underscoring the need for further research and detailed case reporting to inform clinical practice and management.
References:
(1)Guo, H., Zhang, Q., Dai, R., Yu, B., Hoekzema, K., Tan, J., ... & Xia, K. (2020). NCKAP1 disruptive variants lead to a neurodevelopmental disorder with core features of autism. The American Journal of Human Genetics, 107(5), 963-976.