Hyperinsulinism in developmental syndromes.

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Hyperinsulinism causes recurrent, severe hypoglycemia in newborns and infants.
• Several developmental genetic syndromes are associated with hyperinsulinism, but underlying mechanisms are often unclear.
• Beckwith-Wiedemann syndrome (BWS) is the most common associated syndrome, with ~50% of affected children experiencing hyperinsulinism.

Purpose of the Study:

• To review the association between hyperinsulinism and various developmental syndromes.
• To highlight the unclear molecular mechanisms behind hyperinsulinism in these genetic conditions.
• To discuss specific syndromes like BWS, Soto's syndrome, Costello, Timothy, Kabuki, and Congenital Disorders of Glycosylation (CDG).

Main Methods:

• Literature review of genetic syndromes associated with hyperinsulinism.
• Analysis of clinical presentations and known genetic links.
• Focus on the incidence and characteristics of hyperinsulinism in BWS and CDG.

Main Results:

• Hyperinsulinism is a significant feature in BWS, often transient but sometimes requiring intervention.
• Other overgrowth syndromes and rare genetic disorders like Costello, Timothy, and Kabuki syndromes can also present with hyperinsulinism.
• Congenital Disorders of Glycosylation (CDG), particularly CDG-Ib and CDG-Ia, are increasingly recognized causes of hyperinsulinism.

Conclusions:

• Hyperinsulinism is linked to a wide array of developmental syndromes.
• The precise molecular pathways driving hyperinsulinism in most of these syndromes are yet to be elucidated.
• Further research is needed to understand the genetic and molecular basis of hyperinsulinism in these complex conditions.