RT Journal Article
SR Electronic
T1 Congenital hyperinsulinism in children with paternal 11p uniparental isodisomy and Beckwith–Wiedemann syndrome
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 53
OP 61
DO 10.1136/jmedgenet-2015-103394
VO 53
IS 1
A1 Jennifer M Kalish
A1 Kara E Boodhansingh
A1 Tricia R Bhatti
A1 Arupa Ganguly
A1 Laura K Conlin
A1 Susan A Becker
A1 Stephanie Givler
A1 Lindsey Mighion
A1 Andrew A Palladino
A1 N Scott Adzick
A1 Diva D De León
A1 Charles A Stanley
A1 Matthew A Deardorff
YR 2016
UL http://jmg.bmj.com/content/53/1/53.abstract
AB Background Congenital hyperinsulinism (HI) can have monogenic or syndromic causes. Although HI has long been recognised to be common in children with Beckwith–Wiedemann syndrome (BWS), the underlying mechanism is not known.Methods We characterised the clinical features of children with both HI and BWS/11p overgrowth spectrum, evaluated the contribution of KATP channel mutations to the molecular pathogenesis of their HI and assessed molecular pathogenesis associated with features of BWS.Results We identified 28 children with HI and BWS/11p overgrowth from 1997 to 2014. Mosaic paternal uniparental isodisomy for chromosome 11p (pUPD11p) was noted in 26/28 cases. Most were refractory to diazoxide treatment and half required subtotal pancreatectomies. Patients displayed a wide range of clinical features from classical BWS to only mild hemihypertrophy (11p overgrowth spectrum). Four of the cases had a paternally transmitted KATP mutation and had a much more severe HI course than patients with pUPD11p alone.Conclusions We found that patients with pUPD11p-associated HI have a persistent and severe HI phenotype compared with transient hypoglycaemia of BWS/11p overgrowth patients caused by other aetiologies. Testing for pUPD11p should be considered in all patients with persistent congenital HI, especially for those without an identified HI gene mutation.