Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!

At a glance

A form of spinocerebellar ataxia associated with chorioretinal dystrophy and hypogonadotropic hypogonadism.


First described by the English physicians B. J. Boucher and F. B. Gibberd in 1969 in two sisters. The German pediatrician Gerhard Neuhäuser and the German-American geneticist John M. Opitz described four more members of a large family in 1975.


Unknown. Approximately 50 patients have been reported in the literature. There is no sex predilection. The syndrome remains poorly recognized and is probably underreported.

Genetic inheritance

Autosomal recessive pattern of inheritance. The responsible mutations have been mapped to the human PNPLA6 (Patatin-like phospholipase domain containing protein 6) gene on chromosome 19p13.2. PNPLA6 encodes the Neuropathy Target Esterase (NTE) protein and appears to play are role in neuronal growth, retinal development, and two important metabolic pathways. First, being anchored to the cytoplasmic side of the endoplasmic reticulum, it is involved in the metabolism of the key membrane lipid phosphatidylcholine to glycerophosphocholine, which is a precursor in the biosynthesis of the neurotransmitter acetylcholine and thus explains the widespread neurologic and neuroendocrine symptoms associated with its lack or decreased levels. Second, NTE with its phospholipase activity could be involved in the metabolism of lysophosphatidylinositol, which is known to be involved in multiple cellular processes such as cell growth, differentiation, and motility, in a wide variety of cells (including nervous (cerebellum) and endothelial cells.


The tissues involved are all of neuroectodermal origin, however, the exact link between the three features is unclear. The absence of a response to GnRH (Gonadotropin-releasing hormone) stimulation also suggests pituitary gland involvement. The abnormal responses of thyroid-stimulating hormone (TSH) and prolactin to thyrotropin-releasing hormone (TRH), growth hormone to growth hormone releasing hormone (GRH) and insulin-induced hypoglycemia can be used to point toward a hypothalamic involvement.


Based on the clinical findings and family history. CT and/or MRI scans show evidence of cerebellar atrophy. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogen, and testosterone are abnormally low. Ophthalmologic examination will further help to determine the diagnosis. However, confirmation requires molecular genetic testing.

Clinical aspects

Characterized by the triad of spinocerebellar ataxia, chorioretinal dystrophy and hypogonadotropic hypogonadism. The age at onset has two peaks, one-third of patients present in the first decade of life (childhood onset, typically around 6 years of age), while two-thirds present in the second decade of life (typically 15-20 years). However, much later onset is possible. The most frequent symptom in about half the patients at onset is cerebellar ataxia, followed by visual symptoms in about one-third of patients, while signs of hypogonadotrophic hypogonadism are the first symptom in the remainder 20% of patients. Neurological symptoms are typically very slowly progressive. ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.