Isolated Growth Hormone Deficiency due to GH1 Gene Deletion: Central Nervous System Hypertension during Growth Hormone Treatment

Abstract

Background: We report the case of a patient with an uncommon association of isolated growth hormone deficiency (IGHD) due to GH1 gene deletion and Chiari malformation type I. The patient presented with intracranial hypertension during recombinant human GH replacement therapy. Methods: GH deficiency (GHD) was diagnosed based on auxiological data and standard biochemical tests. Molecular analysis of the GH1 gene was performed using polymerase chain reaction amplification and SmaI enzyme restriction. The central nervous system (CNS) was evaluated by computed tomography (CT) and magnetic resonance imaging (MRI). Results: Molecular analysis showed that IGHD was due to homozygotic deletion of the 6.7-kb GH1 gene. After 28 months of GH treatment, CT and MRI scans showed enlargement of the third and lateral ventricles but a normal fourth ventricle, herniation of the cerebellar tonsils by the foramen magnum, presence of dysplastic cerebellar tonsils involving the medulla oblongata, absence of the cisterna magna and compression of the cerebellar tonsils and spinal cord by the posterior arch of the atlas. The patient underwent endoscopic third ventriculostomy, which resulted in complete symptom relief. Conclusions: This case illustrates the importance of CNS evaluation, including detailed examination of the posterior fossa, in patients with GHD.