BACKGROUND: Microdeletions of 14q22q23 have been associated with eye abnormalities and pituitary defects. Other phenotypic features in deletion carriers including hearing loss and response to growth hormone therapy are less well recognized. We studied genotype and phenotype of three newly identified children with 14q22q23 deletions, two girls and one boy with bilateral anophthalmia, and compared them with previously published deletion patients and individuals with intragenic defects in genes residing in the region. RESULTS: The three deletions were de novo and ranged in size between 5.8 and 8.9 Mb. All three children lacked one copy of the OTX2 gene and in one of them the deletion involved also the BMP4 gene. All three patients presented partial conductive hearing loss which tended to improve with age. Analysis of endocrine and growth phenotypes showed undetectable anterior pituitary, growth hormone deficiency and progressive growth retardation in all three patients. Growth hormone therapy led to partial catch-up growth in two of the three patients but just prevented further height loss in the third. CONCLUSIONS: The pituitary hypoplasia, growth hormone deficiency and growth retardation associated with 14q22q23 microdeletions are very remarkable, and the latter appears to have an atypical response to growth hormone therapy in some of the cases.

AP HP Service d'Histologie Embryologie et Cytogénétique Hôpital Antoine Béclère Clamart France

AP HP Service de Biochimie Génétique Plateforme de Génétique Constitutionnelle Hôpital Henri Mondor Créteil France

AP HP Service de Pédiatrie Hôpital Antoine Béclère Clamart France

Department of Biology and Medical Genetics Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Department of Pediatrics Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Genetic and Pediatric Ambulance Benesov Czech Republic

INSERM U935 Villejuif France

INSERM U955 Université Paris 12 Créteil France

Université Paris Sud Faculté de Médecine Paris Sud Le Kremlin Bicêtre France

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Etiology of combined pituitary hormone deficiency: GNAO1 as a novel candidate gene

Haploinsufficiency of BMP4 and OTX2 in the Foetus with an abnormal facial profile detected in the first trimester of pregnancy