Different phenotypes in identical twins with cerebrotendinous xanthomatosis: case series

Abstract

Cerebrotendinous xanthomatosis (CTX) is a rare, genetically determined error of metabolism. The characteristic clinical symptoms are diarrhea, juvenile cataracts, tendon xanthomas and neuropsychiatric alterations. The aim of this study is to present a pair of identical adult twins with considerable differences in the severity of phenotype. With regards to neuropsychiatric symptoms, the predominant features were severe Parkinsonism and moderate cognitive dysfunctions in the more-affected individual, whereas these alterations in the less-affected patient were only very mild and mild, respectively. The characteristic increase in the concentrations of serum cholestanol and the lesion volumes in dentate nuclei in the brain assessed with magnetic resonance imaging were quite similar in both cases. The lifestyle conditions, including eating habits of the twin pair, were quite similar as well; therefore, currently unknown genetic modifiers or certain epigenetic factors may be responsible for the differences in severity of phenotype. This case series serves as the first description of an identical twin pair with CTX presenting heterogeneous clinical features.

Prominent Tendon Xanthomas and Abdominal Aortic Aneurysm Associated with Cerebrotendinous Xanthomatosis Identified Using Whole Exome Sequencing

“…Our patient did not exhibit several symptoms known to be associated with CTX, such as cataract, diarrhea, and neuropathy. It has been reported that the clinical symptoms are quite heterogeneous in this disease, and phenotypes have even been shown to differ in identical twins ( 12 ). Accordingly, it is not yet clear if there are any associations between phenotypes and genotypes in this rare disease.…”

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

“…No correlation has been established between specific mutations and specific clinical features or disease severity (i.e., no genotype-phenotype correlation) (Verrips et al 2000a;Pilo-de-la-Fuente et al 2011). In addition, phenotypic variation within families and among individuals with the same mutation has been reported, including a recently reported case of identical twins who presented with considerably different phenotypes (Verrips et al 2000a;Pilo-de-la-Fuente et al 2011;Zadori et al 2017;Leitersdorf et al 1993;Rosafio et al 2016;Giraldo-Chica et al 2015).…”

The safety and effectiveness of chenodeoxycholic acid treatment in patients with cerebrotendinous xanthomatosis: two retrospective cohort studies

“…Manifestations of CTX can vary, not only within families but even between twins [5]. These include prolonged neonatal jaundice, infantile-onset chronic diarrhoea, juvenile cataracts, tendon xanthomas with onset during adolescence or young adulthood, osteoporosis, and progressive psychiatric and neurological impairment [2,6].…”