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

ABSTRACT

Overgrowth syndromes the practical clinical approach. Excessive growth can be present in a variety of medical conditions as result of abnormal fetal metabolism (i.e., maternal gestational diabetes) or of an overgrowth syndrome. Within this latter group of diseases, a LGA newborn requires a complex differential diagnosis encompassing several syndromes, such as Beckwith-Wiedemman, Sotos, Weaver, Simpson-Golabi-Behmel, Perlman, and Bannayan-Riley-Ruvalcaba. Partial or global overgrowth, other dysmorphisms, abdominal organs anomalies, as well as benign and malignant tumors are the common issues to examine for the diagnosis and the monitoring of all these disorders. The molecular bases of these conditions, even if partially known so far, can help in explaining the clinical features and prognosis. The diagnostic course, the genetic investigations and the follow-up of a LGA patient will be presented during the seminar. A wide clinical spectrum from esophageal atresia to VACTERL association. Oesophageal atresia (OA) occurs approximately in 1 in 3000 live births. It can be clinically divided into isolated and syndromic, when associated with other features. The aetiology is largely unknown and is likely to be multifactorial, however, various clues have been uncovered in animal experiments particularly defects in the expression of the gene Sonic hedgehog (Shh). The vast majority of cases are sporadic and the recurrence risk for siblings is 1%. Survival is directly related to birth weight and to the presence of a major cardiac defect. The VACTERL association refers to anomalies of the bony spinal column (V), atresias in the gastrointestinal tract (A), congenital heart lesions (C), tracheoesophageal defects (TE), renal and distal urinary tract anomalies (R) and limb lesions (L). The overall phenotype of a series of newborn patients we observed may vary widely, reflecting the aetiologic heterogeneity of this group of conditions. Therefore, possible additional defects must be accurately investigated in all newborns with OA.