ESPE Abstracts

Septo-optic dysplasia (SOD) is a rare congenital disorder characterized by a classic triad of optic nerve hypoplasia, agenesis of septum pellucidum and corpus callosum, and hypoplasia of the hypothalamic-pituitary axis. Up to date, a shared consensus is not available and the diagnosis relies mainly on clinical and neuroradiological findings. Even though few genes have been described as responsible for this syndrome, the precise causes of SOD remain unknown and a combination of genetic predisposition and prenatal exposure to environmental factors are believed to play major roles in its occurrence. Here we report the clinical case of a 2 years old boy affected by SOD associated to psychomotor delay, nystagmus, congenital hypothyroidism, and a growth delay. He was born at term after a pregnancy characterized by a decrease of fetal growth since 32th gestational week. At birth the patient presented with adequate length and head circumference but was small for gestational age for weight. Starting from the first month of life he showed psychomotor delay and nystagmus. The newborn screening resulted slightly positive for congenital hypothyroidism; in consideration of the persistent mild neonatal hyperthyreotropinemia (TSH 10-12 mU/L) with FT4 values within, at 30 days of life levothyroxine therapy was started at dosage of 5.7 µg/kg/day. Brain MRI showed a form of SOD characterized by partial segmental agenesis of the corpus callosum, agenesis of the septum pellucidum, optic nerve hypoplasia and a small pituitary gland with small median pituitary stalk. When he was one year old his weight was -3.72 SD, his length -3.27 SD; blood tests showed undetectable IGF1. In consideration of the growth delay and the neuroradiological findings, therapy with growth hormone was started at dose of 0.15 mg/kg/week. A whole exome analysis detected a novel heterozygous de novo variant c.1069_1070delAG in SON gene, reported as pathogenic and responsible of Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a multisystemic neurodevelopmental disorder mainly characterized by intellectual disability, facial dysmorphisms, visual abnormalities, brain malformations, feeding difficulties and growth delay. Peculiar clinical features, neuroradiological findings, multiple hypotalamic-pituitary alterations might suggest the presence of a complex disorder that could not be easly recognised in the first years of life. As far as we know this is the first case of a form of SOD with hypothyoidism in a patient affected by ZTTK syndrome suggesting a possible relationship between septo-optic dysplasia and SON gene alterations. These patients require a longlasting and multidisciplinary follow-up.