Repeat Offenders - Triplet Repeat Disorders
A man develops chorea earlier than his father did. The mutation length increased between generations.
➡ What is anticipation?
Loss of paternal expression on chromosome 15q11–13 causes this syndrome.
➡ What is Prader–Willi syndrome?
Predictive testing for Huntington disease must always be this.
➡ What is voluntary?
Most common cause of sudden cardiac death in young athletes.
➡ What is hypertrophic cardiomyopathy?
This crucial evaluation must occur before ordering Huntington disease presymptomatic testing when a patient presents with distress, depression, or unstable support.
➡ What is a psychosocial assessment?
An HTT allele with 27–35 CAG repeats is not disease-causing but may expand in the next generation.
➡ What are intermediate (mutable normal) alleles?
Loss of maternal expression on chromosome 15q11-13 causes this disorder.
➡ What is Angelman syndrome?
Children are not tested for adult-onset HD because there is no medical benefit and it violates this principle.
➡ What is autonomy?
Two genes responsible for most familial HCM cases.
➡ What are MYH7 and MYBPC3?
Hypotonia + poor feeding + normal microarray → next test.
➡ What is methylation testing for Prader–Willi?
Repeat expansions in Huntington disease tend to occur more often when inherited from the father.
➡ What is repeat instability during spermatogenesis?
First-tier test when PWS or AS is suspected.
➡ What is DNA methylation analysis?
What type of mutation causes Huntington disease?
➡ What is a CAG trinucleotide repeat expansion?
Collapse during swimming is classically associated with this subtype of Long QT syndrome.
➡ What is LQT1?
A genetic disorder shows different phenotypes depending on whether the mutation is inherited from the mother or the father. What genetic principle explains this?
➡ What is genomic imprinting?
This triplet repeat disorder causes intellectual disability due to CGG expansion and gene methylation.
➡ What is Fragile X syndrome?
Two maternal copies of chromosome 15 with no paternal copy cause what syndrome through this mechanism.
➡ What is Prader-Willi syndrome caused by maternal uniparental disomy?
Testing negative for HD does not eliminate risk for this common condition.
➡ What is depression / mental health disorders?
Sudden fainting triggered by loud noises suggests this subtype.
➡ What is LQT2?
This condition arises from a CGG repeat in the 5' UTR of a gene and is associated not with developmental delay, but with tremor, ataxia, and neurodegeneration in older adults who carry a premutation.
➡ What is Fragile X–associated tremor/ataxia syndrome (FXTAS)?
Explain the difference between gain-of-function and loss-of-function triplet repeat disorders.
➡ Gain-of-function = toxic protein (HD)
➡ Loss-of-function = gene silenced by methylation (Fragile X)
Macroglossia, hemihyperplasia, neonatal hypoglycemia suggest this imprinting disorder. Name the most common mechanism.
➡ What is Beckwith-Wiedemann syndrome and what is loss of methyl of IC2 on the maternal chromosome (~50%)
Why must counseling emphasize uncertainty of age of onset?
➡ Repeat length predicts risk, not exact timing.
Borderline QTc with normal testing may occur due to this phenomenon.
➡ What is reduced penetrance?
This inherited electrical disorder, due to a LOF variant, announces itself not in the rush of exertion but in the stillness of the night, when the balance of the autonomic system shifts and the heart’s sodium current falters. Its signature can be uncovered only from the right vantage point, a placement rarely needed in routine screening, and once found, it sends clinicians to examine the rest of the family tree for the same hidden pattern.
➡ What is Brugada syndrome?