Linkage studies in familial idiopathic basal ganglia calcification: Separating the wheat from the chaff

Abstract

Idiopathic Basal Ganglia Calcification (IBGC) is a neuropsychiatric condition characterized by brain calcinosis, heterogeneous motor impairment and behavioral symptoms. The IBGC1 locus was the first region linked to this phenotype in an American family, but another kindred from Spain was also reported as possibly associated with this locus. Our group excluded this locus in additional families together with an independent study of an Australian pedigree with IBGC, but without clinical symptoms. Recently, a large Italian family from a population isolate was excluded from IBGC1. However, there are unusual aspects concerning this Tyrolean family, especially if we consider that almost all the clinically affected subjects manifested symptoms and signs suggestive of a dysmorphic syndrome, associated with neuropsychiatric symptoms. Curiously, some of the clinical features in this kindred match with the autosomal dominant chromosomal instability syndrome reported in Japan. Previous studies show that the definition of an autosomal dominant pattern of inheritance is an assumption that might be considered cautiously in familial IBGC, due to the limited clinical penetrance for the brain calcifications and especially when there is no access to all the parents neuroimaging data. Families from an Italian isolate, such as Tyrol, with high inbreeding rates, are more likely to manifest recessive syndromes. Nevertheless, the current debate regarding the nosology of this heterogeneous phenotype demands the establishment of standard diagnostic criteria. The current identification of loci or mutations responsible for FIBGC might help to elucidate this intriguing neuropsychiatric condition.

2q37 as a Susceptibility Locus for Idiopathic Basal Ganglia Calcification (IBGC) in a Large South Tyrolean Family

“…The nosology of this disorder needs more debate in order to establish standard diagnostic criteria necessary for the identification of loci or mutation responsible for FIBGC (Oliveira and Lemos 2009;. However, given the detailed radiological basis by which BGC was determined and the absence of secondary symptoms, while we cannot rule out that our family represents a novel syndrome, it most certainly resembles more FIBGC than other syndromes such as autosomal dominant chromosome instability syndrome (Ishikawa et al 2000).…”

A young woman with visual hallucinations, delusions of persecution and a history of performing arson with possible three‐generation Fahr disease

“…The disease is classified by intracranial calcification of the basal ganglia with the globus pallidus region being particularly affected (1,2). FD is frequently familial and thought to have autosomal dominant inheritance linked to chromosome 14q (4)(5)(6)(7). FD is frequently familial and thought to have autosomal dominant inheritance linked to chromosome 14q (4)(5)(6)(7).…”

The challenging interpretation of genetic and neuroimaging features in basal ganglia calcification

“…Several other families have been described more recently, and the list grows together with the ramping up of availability of neuroimaging procedures worldwide and with careful screening of patient's relatives [2][3][4][5][6][7].…”

“…Kobari et al (1997) reported a 48-year-old man with intellectual decline, Parkinsonism and mild cerebellar ataxia [5]. Kobari et al (1997) reported a 48-year-old man with intellectual decline, Parkinsonism and mild cerebellar ataxia [5].…”

“…Younger subject free from calcification should be excluded, avoiding the risk of false positive [5]. Individuals with negative computed tomographies (CTs) who are over the age of 50 might be more safely defined as unaffected, while those at earlier ages are classified as unknown, as in previous linkage studies.…”