ESPE Abstracts

Introduction: Orthodenticle homeobox 2 (OTX2) is a transcription factor that plays a critical role in brain and eye development. Heterozygous deleterious mutations in this gene lead to eye malformation such as anophthalmia, microphthalmia, coloboma or optic nerve hypoplasia, normal or hypoplastic pituitary gland and normal or ectopic posterior pituitary gland with isolated growth hormone deficiency or combined pituitary hormone deficiency. There is no genotype – phenotype correlation. Patients with heterozygous OTX2 deletion without eye or pituitary development anomaly have never been reported.

We report on a 3,2 years old boy with a de novo heterozygous deletion of OTX2 without hormonal deficiency or eye malformation.

Case Report: A boy of 3,2 years- old -boy presented to our pediatric endocrinology unit for short stature. He was born at term after an uneventful pregnancy with 3,010 kg and 50 cm. His development was normal. He has familial Mediterranean fever. Parents are non-consanguineous and healthy. The mother's height is 156,3 cm and the father's height is 162 cm (target height -2.2SDS). At first examination his height was 86,4 cm (-2,8 DS), weight 11,05 kg and head circumference 46,8 cm (-3,4 DS). He had no dysmorphic features. The Tanner stage was A1P1G1 with 2 ml testes bilaterally. His growth chart showed a slow postnatal growth. Laboratory analysis showed a normal thyroid function (free T4 18,6 pmol/l), IGF1 was normal for age ( 67 ng/ml and 71 ng/ml), insulin tolerance test showed a good response for both growth hormone and cortisol (GH peak 7,44 ng/ml and cortisol peak 561 nmol/l). Microarray analysis showed a heterozygous deletion of 14q22.3 including the whole OTX2 gene. Both parents had normal microarray results. Cerebral MRI showed a malformation of the pituitary region, with an almost absent sella turcica, normal dimension of the anterior pituitary, with ectopic posterior pituitary gland, a very thin pituitary stalk and no optic nerve malformation. Ophthalmological examination showed no eye malformation or vision problem in our patient.

In conclusion we present on the case of a boy with heterozygous OTX2 deletion who harbors absent sella turcica, ectopic posterior pituitary but neither hormonal deficiencies nor eye malformation.