Haddad syndrome novel association with BRAF mutation

Abstract

This is a report of a 36 week male infant who suffered abdominal distension and difficulty opening bowels within first few days of life and showed a pattern of hypoventilation and apnea associated with sleep. His diagnostic studies confirmed the diagnosis of congenital central hypoventilation syndrome CCHS (PHOX2B mutation) and Hirschsprung's disease and later found a further mutation of BRAF oncogene. This describes a novel association between these mutations and the shared qualities of tumorigenesis between BRAF and PHOX2B.

Research Advances on Therapeutic Approaches to Congenital Central Hypoventilation Syndrome (CCHS)

“…The variable phenotypes reported in CCHS patients carrying the same mutation also suggest the involvement of modifier genes of expressivity (Di Lascio et al, 2018a;Bachetti and Ceccherini, 2020). Mutations in genes other than PHOX2B, involved in the differentiation of neural crest cells (RET, GDNF, BDNF, GFRA1, PHOX2A, HASH-1, EDN1, EDN3, BMP2) or in oncogenes (BRAF) (Bolk et al, 1996;Amiel et al, 1998;Weese-Mayer et al, 2002Sasaki et al, 2003;Fernández et al, 2013;Al Dakhoul, 2017) have been found in some CCHS individuals. Remarkably, some of them are PHOX2B target genes (Flora et al, 2001;Bachetti et al, 2005), but the pathogenic role of these genetic variants is unclear (de Pontual et al, 2007).…”