ABMGG Clinical Genetics & Genomics flashcards

32 cards. Read the term and the definition here. The deck at the top of this page is optional.

Hardy-Weinberg carrier risk

For an autosomal recessive condition with carrier frequency c, disease incidence approximates c²/4 when c is small and mating is random.

Bayesian posterior risk

Posterior odds equal prior odds multiplied by the likelihood ratio of observed test results or pedigree information; convert odds to probability.

Mitochondrial heteroplasmy

Presence of more than one mitochondrial DNA variant within a cell or tissue; clinical expression depends on variant load and tissue threshold.

Genomic imprinting

Parent-of-origin-specific gene expression; disruption causes disorders such as Prader-Willi or Angelman syndrome at 15q11-q13.

Three-generation pedigree

A diagram recording at least grandparents, parents, siblings, and offspring with ages, health status, ancestry, consanguinity, and pregnancy losses.

Dysmorphology red flags

Multiple congenital anomalies, developmental delay, unusual facies, growth abnormality, or familial recurrence warrant syndrome-focused assessment and genetic evaluation.

Developmental regression

Loss of previously acquired skills is a red flag for neurodegenerative or metabolic disease and requires urgent diagnostic evaluation.

Consanguinity risk

Mating between relatives increases the chance that both partners carry the same autosomal recessive variant, raising offspring risk.

Variable expressivity

Individuals with the same pathogenic genotype show different severity or organ involvement, complicating prediction and counseling.

Incomplete penetrance

A pathogenic genotype does not always produce the phenotype; penetrance may be age-dependent and modify recurrence risk.

Anticipation

A disorder appears earlier or more severe in successive generations, classically in repeat-expansion diseases such as Huntington disease.

Pleiotropy

One gene or variant affects multiple organ systems, producing a recognizable pattern of clinical features across the lifespan.

Karyotype versus CMA

Karyotype detects balanced rearrangements and aneuploidy; chromosomal microarray detects submicroscopic copy-number gains and losses with higher resolution.

Exome trio sequencing

Sequencing the proband and both parents improves variant interpretation by identifying de novo and inherited variants and phasing.

Targeted familial variant

Testing only the known pathogenic variant in relatives is faster and cheaper than broad testing; negative results require caution.

Prenatal cfDNA screening

Cell-free DNA screening estimates fetal aneuploidy risk but is not diagnostic; invasive testing confirms positive or high-risk results.

ACMG variant classes

Pathogenic, likely pathogenic, variant of uncertain significance, likely benign, and benign; classification uses evidence criteria and may change over time.

Variant of uncertain significance

A variant with insufficient evidence for pathogenicity; it should not drive clinical management, and periodic reclassification is recommended.

De novo variant evidence

Confirmed de novo occurrence in a proband supports pathogenicity when parentage is verified and the phenotype matches the gene.

Mosaic variant detection

Mosaicism may be missed by blood testing; affected tissue or deeper sequencing improves detection when clinical suspicion is high.

Autosomal recessive recurrence

Carrier parents have a 25% chance of an affected child, 50% carrier child, and 25% unaffected noncarrier child per pregnancy.

X-linked carrier risk

A carrier mother has a 50% chance of transmitting the variant; sons are affected and daughters are carriers.

Bayesian carrier probability

Combine prior carrier risk from pedigree or population frequency with test sensitivity and specificity to calculate posterior carrier probability.

Teach-back communication

Asking patients to explain the information in their own words confirms understanding and reveals gaps in genetic risk communication.

Enzyme replacement therapy

For selected lysosomal storage disorders, exogenous enzyme reduces substrate accumulation and improves systemic manifestations, but neurological benefit varies.

Substrate reduction therapy

Oral small molecules reduce synthesis of disease-causing metabolites, offering an alternative for some metabolic disorders.

Reproductive genetic options

Prenatal diagnosis, preimplantation genetic testing, donor gametes, and adoption allow families to manage recurrence risk.

Transition of care

Planned movement from pediatric to adult multidisciplinary services prevents gaps in surveillance and treatment for chronic genetic conditions.

GINA protections

In the United States, GINA limits genetic discrimination in health insurance and employment but not life, disability, or long-term care insurance.

Duty to warn

Confidentiality may be breached when a genetic condition poses a serious, actionable risk to relatives, following legal and ethical standards.

Assent for minors

Children should participate in decisions about genetic testing through developmentally appropriate assent, while parents provide legal consent.

Secondary findings policy

Clinicians should disclose whether medically actionable incidental findings will be reported and honor patient preferences consistent with guidelines.