ESPE Abstracts (2014) 82 P-D-2-2-461

Anophthalmia, Abnormal Pituitary Development, and Suboptimal Response to GH Therapy in Two Children With Microdeletions of 14q22q23

Petra Dusatkovaa, Zuzana Slamovab, Zdenek Sumnika, Martina Simandlovab, Elsa Zemankovac, Zdenek Sedlacekb & Jan Lebla

aDepartment of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic; bDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic; cGenetic and Pediatric Out-Patient Clinic, Benesov, Czech Republic

Background: Microdeletions of 14q22q23 have been associated with eye abnormalities. Other symptoms in deletion carriers are less well recognized.

Objective and hypotheses: We focused on growth characteristics and response to GH treatment in two unrelated children with 14q22q23 deletions.

Method: Array comparative genomic hybridisation (aCGH).

Results: Both patients displayed bilateral anophthalmia. Their brain MRI revealed absence of optic nerves and chiasm; the pituitary stalk and posterior pituitary were normally located, but the anterior pituitary was undetectable. Both children suffered from GH deficiency. The initially normal growth of patient 1 started to decelerate at 10 months and reached −1.8 S.D. at 1.8 years. At this time GH therapy (25 μg/kg per day) was initiated. It improved the growth rate and the serum IGF1 level but did not lead to full catch-up growth (−1.9 S.D. at 3.1 years). In contrast to patient 1, patient 2 was born with IUGR that was followed by severe postnatal growth failure (−3.7 S.D. at 1.5 years). GH therapy (25 μg/kg per day) initiated at the age of 2.3 years led to an improved height velocity in the first year of GH administration but without full catch-up (−4.0 S.D. at 3.2 years). Also the serum IGF1 level remained low. Other pituitary functions were normal in both patients. aCGH revealed heterozygous de novo deletions of 8.9 and 5.8 Mb in patients 1 and 2, respectively. Both deletions removed the OTX2 gene, critical for eye and pituitary development. No other gene related to growth has been detected in the deleted region.

Conclusion: Genotype–phenotype description of two patients with deletions of 14q22q23 demonstrated that OTX2 gene defects alone could explain most of the reported clinical features, although their expressivities are very variable. GH deficiency is remarkable in these patients and may be difficult to correct with GH therapy.

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