GENETIC DISEASES
Key features
Accurate information about phenotype and family history is essential in identifying the pattern of inheritance of a genetic disease
Genetic diseases include Mendelian (monogenic) disorders caused by defects in one gene as well as polygenic disorders due to defects in more than one gene; complex (multifactorial) disorders result from the interaction of environmental and genetic factors
The major Mendelian patterns of inheritance are autosomal recessive (e.g. oculocutaneous albinism), autosomal dominant (e.g. Darier disease), X-linked recessive (e.g. hypohidrotic ectodermal dysplasia), and X-linked dominant (e.g. incontinentia pigmenti)
Factors modifying the basic Mendelian pattern of inheritance include incomplete penetrance, age-dependent penetrance, variable expression, de novo mutations, pseudodominant inheritance, genomic imprinting, and mitochondrial inheritance
Chromosomal anomalies can consist of abnormalities in the number (e.g. polyploidy, aneuploidy) or structure (e.g. translocations, inversions) of the chromosomes
Heterogeneity at the locus or allelic level can make identification of the genetic defects responsible for cutaneous disorders challenging
Genetic diseases can manifest in multiple members of a family. However, not every disease presenting in more than one family member is genetic. Pedigrees of families in which a genetic disease is transmitted (i.e. segregates or is inherited) can range from a single affected member to many affected members in several generations.
Mendelian (monogenic) diseases are caused by defects in one gene, while polygenic diseases result from defects in more than one gene and complex (multifactorial) diseases result from the interaction of environmental and genetic factors. In addition to mutations within particular genes, abnormalities in the structure, number, or parental contribution of chromosomes can cause disease.
In the following sections, we provide an overview of the different types of genetic diseases. While this chapter focuses on genodermatoses, the explanations of Mendelian and complex traits also apply to extracutaneous diseases.