Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.
Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration.


CONCLUSIONS
Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.
Department of Paediatrics, Midland Regional Hospital, Mullingar, Co. Westmeath, Ireland.
Aisling M
AM
O'Riordan
Department of Paediatrics, Midland Regional Hospital, Mullingar, Co. Westmeath, Ireland.|Department of Paediatric Endocrinology, Temple Street Children's University Hospital, Dublin 1, Ireland.
Niamh
N
McGrath
Department of Paediatrics, Midland Regional Hospital, Mullingar, Co. Westmeath, Ireland.|Department of Paediatrics, Royal College of Surgeons Ireland (RCSI), Dublin 2, Ireland.
Farhana
F
Sharif
Department of Paediatric Endocrinology, Temple Street Children's University Hospital, Dublin 1, Ireland.|UCD School of Medicine, University College Dublin, Dublin 4, Ireland.
Nuala P
NP
Murphy
Department of Paediatric Cardiology, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
Orla
O
Franklin
UCD Academic Centre on Rare Diseases, University College Dublin, Dublin 4, Ireland.|Department of Clinical Genetics, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland.
Sally Ann
SA
Lynch
Department of Paediatrics, Midland Regional Hospital, Mullingar, Co. Westmeath, Ireland. michaelogrady@physicians.ie.
Michael J
MJ
O'Grady
D001021:Aortic Valve; D000067877:Autism Spectrum Disorder / Q000175:diagnosis; D000082882:Bicuspid Aortic Valve Disease; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005183:Failure to Thrive / Q000209:etiology; D005260:Female; D006130:Growth Disorders / Q000235:genetics*; D057895:Haploinsufficiency; D006330:Heart Defects, Congenital / Q000235:genetics; D006349:Heart Valve Diseases / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male
D007334:Insulin-Like Growth Factor I
15q26 deletion; Aortic root; Developmental delay; Growth; IGF-1 receptor