ESPE Abstracts

Introduction: Complex diseases are defined by the interference of different genetic and environmental factors and the contribution of each factor is often hard to unravel. In this report, we present a case where different complex diseases intertwine.

Case report: We report the case of a 12 month old girl who was addressed to the endocrinology department due to hypotonia and short stature. The pregnancy had been uneventful and somatometry at birth was normal. At the first visit, her weight was at -1.6 DS and her length at -2.0 DS. Some dysmorphic features were noticed, such as triangular shaped face and prominent ears. Workup revealed a central hypothyroidism and growth hormone testing showed deficiency. Magnetic resonance imaging displayed a small pituitary gland with an ectopic neurohypophysis. The karyotype was 46, XX. Replacement therapy with levothyroxine and growth hormone was started with a positive response, although a development delay and strabismus became apparent throughout follow up. Genetic testing had been unremarkable. The patient had a first seizure at the age of 10, starting anti-convulsive therapy at that time. Genetic testing was reprised and a mendeliome testing revealed a pathogenic variant compatible with Koolen de Vries syndrome. At the age of 12, the patient was addressed to the Emergency Room due to vomiting and fatigue. The mother had also noted a relative polydipsia and polyuria. While the ionogram was normal, blood glucose was of 423 mg/dL and blood ketones were high. A low pH confirmed the diagnosis of diabetic ketoacidosis. Antibodies to glutamic acid decarboxylase, IA2 and insulin were positive, corroborated an auto-immune aetiology. The patient has recently started therapy with an automated insulin delivery system, with stable glycemic control.

Conclusion: Koolen de Vries syndrome is associated with dysmorphic features, development delay and hypotonia. While other structural cerebral malformations have been described, including one case report featuring a pituitary stalk interruption, an ectopic neurohypophysis has not been described, to the best of our knowledge. Furthermore, the concomitant occurrence of diabetes doesn’t seem to share a common pathogenic background, adding complexity to an already challenging case.