Two Sisters with Kallmann Syndrome, Gonadal Dysgenesis, and Multiple Neuromuscular and Endocrine Disorders: Report of Two Cases with Description of an Unusual Association

Abstract

AbstractKallmann syndrome (KS) is an uncommon genetic disorder characterized by isolated congenital hypogonadotropic hypogonadism (CHH) and anosmia/hyposmia. KS originates from abnormal embryonic migration of olfactory axons and gonadotropin-releasing hormone (GnRH)-synthesizing neurons. It can be challenging to diagnose due to its heterogeneous clinical presentation and genes implied. Herein, we report a rare phenotype of KS in two sisters accompanied by a variety of nonreproductive disorders such as hypoparathyroidism, hypercortisolism, atrophy of the cerebellum, intellectual disability, and remarkably, ovarian dysgenesis. Additionally, both subjects present muscle weakness, exercise intolerance, marked hypotonia and seizures, being suspected, although not fully confirmed, mitochondrial encephalomyopathy. These cases illustrate the heterogeneous clinical presentation and the diagnostic difficulties often found in patients suffering from this condition. These clinical features have never been described before as associated with KS; therefore, we decided to report this novel KS phenotype.