Fragile X Syndrome: A Rare Case of a Female Carrier Exhibiting the Phenotypic Spectrum of Disease Features

Abstract

Fragile X Syndrome is an X-linked recessive mutation in the Fragile X Mental Retardation 1 (FMR1) gene that results in CGG trinucleotide repeats in the 5’ untranslated arm of the FMR1 gene resulting in methylation that silences and/or reduces gene expression. The condition that manifests along a spectrum of symptoms depending on the number of repeats, where a premutation (defined as 55 to 200 CGG repeats) presents with less severe symptoms compared to a full mutation (>200 repeats). The full mutation tends to be more male predominant (85%), while the premutation tends to affect females more who are carrier of this condition [1]. The premutation condition is divided into two subtypesFragile X-associated Primary Ovarian Insufficiency (FXPOI) and Fragile X-associated Tremor/ Ataxia Syndrome (FXTAS) [2]. Although both conditions manifest with psychiatric conditions, they possess unique features on presentation where FXPOI occurs in 20% of female carriers and presents with menopause before the age of 40, while FXTAS occurs in 16% of females and presents with neurological symptoms, including intention tremors, ataxic gait, autonomic dysfunction, neuropathy, and Parkinsonism [3]. Although the psychiatric disorders common to both conditions tend to be depression and/or anxiety, they can also include psychosis and memory and executive function deficits in more advanced cases [4]. Studies have shown that in FXTAS the psychiatric symptoms manifest before the neurological conditions [5]. Studies have also noted an association between the cognitive decline in carriers of this mutation and increased substance abuse that patients fail to acknowledge as abnormal [6,7]. Due to the dearth of Fragile X carrier cases in the literature, there are few observed cases that can document the extent of this condition. Herein, we present a case of female adult carrier who has uniquely displayed the spectrum of systemic manifestations since menarche.