Genetic syndrome suspicion: examples of clinical approach in the neonatal unit

Area of Science:

• Pediatric Endocrinology
• Clinical Genetics
• Neonatology

Background:

• Excessive fetal growth, resulting in Large for Gestational Age (LGA) newborns, can originate from maternal gestational diabetes or specific overgrowth syndromes.
• Key overgrowth syndromes include Beckwith-Wiedemann, Sotos, Weaver, Simpson-Golabi-Behmel, Perlman, and Bannayan-Riley-Ruvalcaba, presenting with diverse clinical features.
• Esophageal atresia (OA) and VACTERL association represent significant congenital anomalies with complex etiologies and varied clinical presentations.

Purpose of the Study:

• To outline a practical clinical approach for diagnosing and managing LGA newborns with potential overgrowth syndromes.
• To discuss the differential diagnosis, common clinical issues, and molecular underpinnings of various overgrowth disorders.
• To present the diagnostic course, genetic investigations, and follow-up strategies for LGA patients, as well as the spectrum of anomalies in OA and VACTERL association.

Main Methods:

• Review of clinical presentations and diagnostic criteria for major overgrowth syndromes.
• Analysis of common features such as partial or global overgrowth, dysmorphisms, abdominal organ anomalies, and tumor risks.
• Examination of the etiology, genetic factors, and clinical management of esophageal atresia and VACTERL association.

Main Results:

• LGA newborns require a complex differential diagnosis to identify specific overgrowth syndromes.
• Overgrowth syndromes share common issues including dysmorphisms, organ anomalies, and increased tumor risk, necessitating careful monitoring.
• Esophageal atresia and VACTERL association exhibit a wide clinical spectrum, with etiologies often multifactorial and survival dependent on associated defects.

Conclusions:

• A systematic diagnostic and genetic investigation approach is essential for managing LGA newborns with suspected overgrowth syndromes.
• Understanding the molecular basis of these syndromes aids in predicting clinical features and prognosis.
• Comprehensive evaluation for additional defects is critical in newborns with esophageal atresia and VACTERL association due to their potential heterogeneity.