"Genetic disorder" gets used as if it names one kind of thing, but the underlying causes actually split into three genuinely distinct categories, operating at very different scales. A chromosomal disorder involves an entire chromosome, or a large piece of one, being duplicated, missing or rearranged. A single-gene disorder traces back to a fault in one specific gene, following predictable inheritance patterns. A multifactorial disorder instead arises from many genes acting together, often combined with environmental influences, with no single gene or chromosome fully accounting for it on its own.
Chromosomal disorders involve far more genetic material going wrong at once
Chromosomal disorders arise when cell division goes wrong at a much larger scale than a single gene, typically during the formation of egg or sperm cells, resulting in a person having an extra copy of an entire chromosome, a missing chromosome, or a chromosome with a large structural rearrangement. Down syndrome, involving an extra copy of chromosome 21, is a well-known example: because an entire extra chromosome, carrying hundreds of genes rather than just one, is involved, the resulting effects tend to be broad and to affect multiple body systems simultaneously, rather than the narrower, more specific effects a single faulty gene typically produces.
Single-gene disorders follow predictable inheritance, multifactorial ones don't
Single-gene disorders, by contrast, trace back to a fault in one specific gene, and because they involve just one gene, they tend to follow the same predictable inheritance patterns Mendel originally described — dominant, recessive, or sex-linked — making it possible, in principle, to calculate a family's precise risk of a child inheriting the condition from parents whose own genetic status is known. Multifactorial disorders, which include many common conditions like most cases of heart disease or diabetes, don't follow any single clean inheritance pattern at all, because they arise from the combined, cumulative effect of many different genes, each contributing only a small individual effect, further combined with environmental and lifestyle factors — which is exactly why multifactorial conditions tend to run in families in a much less predictable, more probabilistic way than a clean single-gene disorder does, and why no simple Mendelian calculation can capture a family's risk the way it can for a genuinely single-gene condition.
What we're still unsure about
The three-way distinction between chromosomal, single-gene and multifactorial disorders, and the well-documented examples within each category, are well-established, thoroughly confirmed medical genetics. What remains a genuinely active area of ongoing research is precisely how many distinct genes, and which specific environmental factors, actually contribute to a given multifactorial condition, and in what combination — for most multifactorial disorders, researchers have identified some, but very likely not all, of the relevant genetic contributors, and the exact weighting between genetic and environmental influence for a specific individual's own risk remains considerably harder to pin down than it is for a clean single-gene condition with a fully characterised inheritance pattern.
This sits inside Genetic & Developmental Disorders, one of seven topics in Pathology, one of four domains in Medicine, one of seventeen subjects the app can quiz you on.