Monogenic Diseases and Mendelian Inheritance Flashcards

Vocabulary practice flashcards covering Mendelian inheritance patterns, autosomal dominant/recessive disorders, X-linked dominant/recessive diseases, and genetic mechanisms.

Mendelian Disorders

Single gene disorders classified according to whether they are autosomal or X-linked and whether they exhibit a dominant or recessive pattern of inheritance.

Vertical Inheritance

The transmission pattern of a trait or disease from parent to offspring across successive generations, characteristic of autosomal dominant inheritance.

Variable Expressivity

Variations in the severity or range of clinical phenotype expressed by individuals carrying the exact same genotype.

Complete Penetrance

A condition in which every individual carrying a specific disease-causing allele displays clinical symptoms of the disease.

Incomplete Penetrance

A situation where some individuals who carry a pathogenic gene mutation fail to express the associated clinical phenotype.

Neurofibromatosis Type 1 (NF1)

An autosomal dominant disorder diagnosed when meeting two or more specific criteria, such as $\ge 6$ café-au-lait spots, $\ge 2$ neurofibromas, axillary or groin freckling, optic glioma, $\ge 2$ Lisch nodules, bone lesions, or an affected first-degree relative.

Lisch Nodules

Benign iris hamartomas that serve as a characteristic diagnostic criterion for Neurofibromatosis type 1.

Achondroplasia

An autosomal dominant bone growth disorder characterized by short stature, rhizomelic shortening of long bones, trident hand configuration, bow legs (genu varum), exaggerated lumbar lordosis, and macrocephaly with frontal bossing.

Rhizomelic Shortening

Disproportionate shortening of the proximal segments of the limbs (the humerus in arms and femur in legs), commonly seen in achondroplasia.

Marfan Syndrome

An autosomal dominant connective tissue disorder presenting with high stature, dolichocephaly, arachnodactyly, joint hypermobility, thoracic deformities, lens dislocation, and aortic dilation or dissection.

FBN1 Gene

The gene located on chromosome 15q21 that encodes fibrillin-1, mutations in which cause Marfan syndrome.

Consanguinity

Genetic relatedness between mating partners, which increases the likelihood that both parents carry the same rare recessive disease allele.

Haplosufficiency

A genetic condition in autosomal recessive heterozygotes where a single functional wild-type allele produces enough active protein to meet the cell's operational requirements.

Genetic Complementation

The phenomenon where offspring produced by parents with the same recessive phenotype display a normal phenotype because each parent carries mutations in different genes.

Sickle Cell Anemia (HbSS)

An autosomal recessive hemoglobinopathy caused by a point mutation in the 6th codon of exon 1 of the $\beta$-globin gene ($\text{GAG} > \text{GTG}$) substituting Glutamic Acid with Valine.

Dactylitis

Painful swelling of the hands or feet caused by microvascular occlusion of small bones, also known as hand-foot syndrome, which occurs in infants and young children with sickle cell disease.

Fragile X Syndrome

An X-linked dominant condition and the leading cause of inherited intellectual disability, caused by trinucleotide CGG repeat expansion in the $FMR1$ gene, clinically featured by long face, large ears, prominent jaw, and macroorchidism.

Incontinentia Pigmenti

An X-linked dominant multisystem neurocutaneous disorder characterized by skin pigmentation anomalies, alopecia, dental abnormalities, and neurological deficits, which is lethal in hemizygous male fetuses.

Duchenne Muscular Dystrophy (DMD)

An X-linked recessive progressive muscular dystrophy usually diagnosed around age 4, causing loss of ambulation by age 12 and cardiac/respiratory failure in young adulthood, caused by mutations in the $DMD$ gene.

Hypohydrotic Ectodermal Dysplasia

An X-linked recessive disorder characterized by defective development of ectodermal structures, leading to anhidrosis, anodontia, sparse hair, and iris abnormalities.

X-Chromosome Inactivation (Lyonization)

The random embryonic process in female mammals where one of the two X chromosomes in each cell is silenced and condensed into transcriptionally inactive heterochromatin.

Barr Body

The dense, condensed mass of inactivated X heterochromatin visible in the interphase nucleus of mammalian cells, equal in quantity to $n - 1$ where $n$ is the total number of X chromosomes.

Co-dominance

An inheritance pattern in which both alleles in a heterozygous gene pair are fully expressed and detectable in the individual's phenotype, such as the AB genotype in the ABO blood group system.