Multifactorial Inheritance

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance, as well as relative insulin deficiency. Genetically determined causes of diabetes (e.g., maturity-onset diabetes of the young and late autoimmune diabetes in adults) are being increasingly recognized, but they make up a small portion of cases. There is no definitive cure for DM. The objective of management is the prevention of complications, which may include coronary artery disease, CKD, retinopathy, and neuropathy. Long-term monitoring and maintenance of optimal blood glucose levels are key to preventing complications. Treatment is specific to the type of diabetes, with glycemic control as the goal in all types; insulin replacement is essential in type 1, and a healthy diet, lifestyle changes, and medications are important in type 2.

Hirschsprung disease (HD), also known as congenital aganglionosis or congenital megacolon, is a congenital anomaly of the colon caused by the failure of neural crest-derived ganglion cells to migrate into the distal colon. The lack of innervation always involves the rectum and extends proximally and contiguously over variable distances. Most cases are diagnosed in the neonatal period, with a classic triad of symptoms including delayed passage of meconium, abdominal distension, and bilious vomiting. Individuals having less severe degrees of functional obstruction may not be diagnosed until later in infancy or childhood when they present with symptoms of chronic refractory constipation, abdominal distension, and failure to thrive. The diagnosis of HD is confirmed by the absence of ganglion cells on rectal biopsy after noninvasive testing such as anorectal manometry and the use of contrast enema. Surgical resection of the aganglionic segment is the standard treatment.

Deep vein thrombosis (DVT) is a blood clot in the deep veins, usually in the lower extremities (though they can occur in the upper extremities, mesenteric, and cerebral veins as well). The affected veins commonly include the popliteal, femoral,  iliac, and pelvic veins. The 3 primary factors (known as the Virchow triad) that contribute to DVT formation include: venous stasis, hypercoagulability, and vascular endothelial damage. Any condition that worsens 1 (or more) of these 3 factors increases the risk of DVT formation. Individuals can present with unilateral extremity pain, swelling, and/or redness around the DVT; however, a majority of cases are asymptomatic. Ultrasound can visualize the thrombus. Anticoagulation is the primary mode of treatment; the main objective is preventing a pulmonary embolism (PE).

Gregor Mendel (1822–1884), the "father of genetics", was an Augustine monk and mathematician who performed cross-breeding experiments with peas and beans from a monastery garden. Based on the experiments, Mendel deduced hereditary factors may be passed from the parental generation to the filial generation. From the deductions, the father of genetics formed Mendel's laws of heredity: the law of segregation, the law of independent assortment, and the law of dominance. Mendel's laws described the inheritance of uncoupled autosomal genes based on statistical predictions. The gene traits follow the laws of mendelian inheritance.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of

Hirschsprung disease (HD), also known as congenital aganglionosis or congenital megacolon, is a congenital anomaly of the colon caused by the failure of neural crest-derived ganglion cells to migrate into the distal colon. The lack of innervation always involves the rectum and extends proximally and contiguously over variable distances. Most cases are diagnosed in the neonatal period, with a classic triad of symptoms including delayed passage of meconium, abdominal distension, and bilious vomiting. Individuals having less severe degrees of functional obstruction may not be diagnosed until later in infancy or childhood when they present with symptoms of chronic refractory constipation, abdominal distension, and failure to thrive. The diagnosis of HD is confirmed by the absence of ganglion cells on rectal biopsy after noninvasive testing such as anorectal manometry and the use of contrast enema. Surgical resection of the aganglionic segment is the standard treatment.

Bipolar disorder is a highly recurrent psychiatric illness characterized by periods of manic/hypomanic features (distractibility, impulsivity, increased activity, decreased sleep, talkativeness, grandiosity, flight of ideas) with or without depressive symptoms. The etiology is unknown but is believed to be a complex interplay of different factors: genetic, neurobiologic, and environmental. Diagnosis is clinical, with the help of screening tools to determine mood and depression symptoms. Underlying substance use or medical conditions need to be ruled out with laboratory and imaging tests if indicated. Treatment of bipolar disorder varies based on the presenting features but usually involves pharmacotherapy with lithium, valproic acid, and/or antipsychotic medications. Other methods include psychotherapy and somatic therapies. Acute severe mania is a medical emergency and generally requires hospitalization. Maintenance therapy is typically necessary to reduce symptoms, prevent new mood episodes, decrease risk of suicide, and improve overall psychosocial functioning.

Genetics is the study of genes and their functions and behaviors. Genetics is an important topic for board examinations, and a thorough understanding of different words used in the study of genetics is an important piece of knowledge. Crucial terms in the study of genetics are listed and defined below, in alphabetical order.

Population genetics is a field in genetics that is concerned with the differences in the gene pool between different populations and how this underlies phenotypic differences between populations. The Hardy-Weinberg equilibrium serves as a basis for studying genetic variation within a population and allows for the calculation of allelic frequency. The process of natural selection is what determines the allelic frequencies in the population and the variability in the genotype-phenotype relationships between species.

As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Several genetic defects and risk factors have been described, although there is no clear cause in the majority of cases. The main pathologic features are neuritic plaques, extracellular deposits of amyloid peptides, and neurofibrillary tangles. The clinical features are memory impairment, loss of executive function and judgment, impaired cognitive function, and behavioral changes. Diagnosis is based on clinical examination, neuropsychiatric testing, and imaging. There is no curative therapy, but symptomatic management with medications may slow progression; these include cholinesterase inhibitors, the N-methyl-D-aspartate (NMDA) receptor antagonist memantine, and a recently approved anti-amyloid monoclonal antibody.

Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. The myocardium becomes ischemic when oxygen supply does not meet oxygen demand. Diagnosis is based on history and ECG findings; cardiac stress tests and catheterizations may also be needed. Treatment is primarily based on reducing the heart's oxygen demand and increasing the delivery of oxygen.

Deep vein thrombosis (DVT) usually occurs in the deep veins of the lower extremities. The affected veins include the femoral, popliteal, iliofemoral, and pelvic veins. Proximal DVT is more likely to cause a pulmonary embolism (PE) and is generally considered more serious. Ultrasound can visualize the thrombus and anticoagulation is the primary mode of treatment; the main objective is the prevention of development of a PE.