Accelerate the Diagnostic Path after Feature Presenting in Primary Care

Background: World-wide children are enrolled in preventive child health schemes including vaccination, growth and development surveillance. Deviation in growth or development and typical features are often the first sign of what could be a rare and disabling condition. While the symptoms are present and recognized their cause may remain undiagnosed. Even though genetic diagnostic panels and chromosome studies are becoming more available in practice.

Objective: Demonstrate how selected Whole Exome Sequencing (WES) panels and chromosome analysis can help to establish a diagnosis and underline what could be the associated health risks.

Methods: We selected 3 cases in preventing child health care, with recognizable features and identified the novel diagnostic test leading to a diagnosis.

Results: -Intellectual disability: a 2-year-old girl with obvious developmental delay. She was in foster care. With a WES panel on intellectual disability, a mutation in NAA15 was established. The NAA15 mutation causes autism and speech problems as well as an elevated risk of a heart defect.

-Facial Dysmorphism: a 2-year-old girl child with an asymmetric face. This could be caused by unilateral craniosynostosis of the coronal suture. With a WES panel on craniofacial anomalies, the genetic aetiology can directly be established, reducing numerous radiologic investigations such as aa X skull and MRI.

-Growth delay: a 12 months old girl with reduced growth in length and weight and minor dysmorphic features. The child has a small chromosomal abnormality detected by a microarray, which also causes an aberrant speech development.

Conclusion: Symptom-driven genetic testing can fasten pathways to correct diagnosis and reduce less accurate and often more complicated diagnostic procedures. Gene panels have to be considered in developmental delay, growth disturbances and diversity of congenital anomalies. It should be remembered the chromosomal anomalies, maybe missed with specific WES gene panels.