Clinical and neuroimaging review of triplet repeat diseases

Abstract

Triplet repeat diseases (TRDs) refer to a group of diseases caused by three nucleotide repeats elongated beyond a pathologic threshold. TRDs are divided into the following four groups depending on the pathomechanisms, although the pathomechanisms of several diseases remain unelucidated: polyglutamine disorders, caused by a pathologic repeat expansion of CAG (coding the amino acid glutamine) located within the exon; loss-of-function repeat disorders, characterized by the common feature of a loss of function of the gene within which they occur; RNA gain-of-function disorders, involving the production of a toxic RNA species; and polyalanine disorders, caused by a pathologic repeat expansion of GCN (coding the amino acid alanine) located within the exon. Many of these TRDs manifest through neurologic symptoms; moreover, neuroimaging, especially brain magnetic resonance imaging, plays a pivotal role in the detection of abnormalities, differentiation, and management of TRDs. In this article, we reviewed the clinical and neuroimaging features of TRDs. An early diagnosis of TRDs through clinical and imaging approaches is important and may contribute to appropriate medical intervention for patients and their families.

Infantile‐onset parkinsonism, dyskinesia, and developmental delay: do not forget polyglutamine defects!

“… 21 Trinucleotide repeat expansion analysis is not included (or covered by insurance) in the genetic workup of infantile or childhood‐onset neurodegenerative movement disorders, especially in the absence of a significant familial history and the role of polyglutamine defect is probably underrecognized. 22 Our case highlights that polyglutamine diseases should be considered, even in infantile‐onset neurodegenerative diseases without family history. However, polyQ detection raised ethical issues; delineation of the spectrum of polyglutamine defects in infants and children will be necessary meanwhile novel techniques for genome‐wide evaluation of repeat expansions are under development and validation.…”

“…Recently, a high prevalence of individuals carrying intermediate or pathological ranges of polyglutamine disease‐associated alleles among the general population has been reported 21 . Trinucleotide repeat expansion analysis is not included (or covered by insurance) in the genetic workup of infantile or childhood‐onset neurodegenerative movement disorders, especially in the absence of a significant familial history and the role of polyglutamine defect is probably underrecognized 22 . Our case highlights that polyglutamine diseases should be considered, even in infantile‐onset neurodegenerative diseases without family history.…”

Postpartum Hypophysitis: A Case Report and a Literature Review

“…Additionally, a rare type of primary hypophysitis predominantly affecting the female population is xanthomatous hypophysitis, histologically different from other subtypes (infiltration of foamy histiocytes) but clinically can be similar to LHy [3]. Gadolinium-enhanced magnetic resonance imaging (MRI) is very helpful and helps prevent invasive diagnosis with biopsy [4].…”