Basic Neurosciences · Paper A
Inheritance patterns
A family tree, or pedigree, reveals the inheritance pattern of a genetic condition through specific, recognisable clues, before any genetic test is done. A pedigree showing the condition in every generation, affecting both sexes, with clear father-to-son transmission, points to autosomal dominant inheritance: often faster than waiting for a genetic test.
Autosomal dominant conditions show a vertical pattern through successive generations, affect both sexes, allow male-to-male transmission, and give each child of an affected parent a 50% risk, as in Huntington's disease. Neurofibromatosis type 1 (caused by NF1 mutations on chromosome 17) and Pick's disease/frontotemporal dementia are further named autosomal dominant examples. Autosomal recessive conditions can appear in siblings born to unaffected carrier parents, affect both sexes, may show consanguinity (parents being blood relatives), and give each pregnancy between two carriers a 25% risk. X-linked recessive conditions mainly affect males, show no father-to-son transmission, and an affected father makes all his daughters carriers if the mother is unaffected. Hunter syndrome (mucopolysaccharidosis type II) and Duchenne muscular dystrophy are named X-linked recessive examples. Both can show a skip-generation pedigree, an affected maternal grandfather having an affected grandson through an unaffected carrier daughter, sometimes called the 'knight's move' pattern after the chess piece's diagonal jump across the pedigree. Females carry two X chromosomes, and random X-inactivation (Lyonization) silences one X per cell, producing a functional mosaic. This is why heterozygous carrier females of an X-linked recessive condition are usually unaffected or only mildly affected, unlike hemizygous males who express whichever allele their single X carries. X-linked DOMINANT inheritance is a separate, less common pattern. Like X-linked recessive, an affected father shows no father-to-son transmission and passes the condition to all of his daughters. Unlike X-linked recessive, heterozygous carrier females are themselves affected (transmitting to about half their children of either sex) rather than being unaffected carriers. Rett syndrome, caused by a de novo (new, not inherited from a parent) MECP2 mutation, and Fragile X syndrome (with reduced penetrance, meaning not everyone carrying the mutation shows the full phenotype) are both classed as X-linked dominant. Mitochondrial conditions pass from an affected mother to children of either sex, but never from an affected father. A pedigree where only males are affected, with no father-to-son transmission anywhere, points specifically to X-linked recessive inheritance. E.g., a pedigree with affected males only, skipping generations through unaffected carrier daughters, points to X-linked recessive inheritance. Not every condition is inherited at all: Klinefelter syndrome (47,XXY) arises sporadically from meiotic nondisjunction (a chromosome-separation error during egg or sperm formation), not from a transmitted gene, so it does not follow a Mendelian ratio and is not usually seen recurring in a family.
Every inheritance-pattern question hides the same trick: it gives you a family tree, or PEDIGREE (a diagram showing a family across generations, using squares for males, circles for females, and shading for who is affected), and asks you to name the pattern before any genetic test result is even mentioned. Getting fast at reading two simple clues off that diagram, which sexes are affected, and whether an affected father ever has an affected son, solves most of these questions in under thirty seconds. Everything below builds toward that one skill.
An inheritance pattern is the rule that predicts how a genetic condition is passed from parent to child, based on which chromosome carries the faulty gene and how many copies of that gene are needed to cause disease. The four patterns tested most often are autosomal dominant, autosomal recessive, X-linked recessive, and mitochondrial. Each has a distinctive fingerprint on a pedigree, and learning that fingerprint is far more useful than memorising a list of example diseases.
Many candidates try to recognise a pattern by memorising which named diseases go with which pattern. This collapses instantly under exam pressure with an unfamiliar disease name. The far more reliable method is to read the PEDIGREE itself: count generations affected, check both sexes, and specifically hunt for father-to-son transmission, since that single observation is the fastest way to rule X-linked recessive in or out.
Humans have 23 pairs of chromosomes: 22 pairs of AUTOSOMES (the non-sex chromosomes, numbered 1 to 22) plus one pair of sex chromosomes (XX in females, XY in males). A gene fault on an autosome can affect either sex equally, because both sexes carry two copies of every autosome. A gene fault on the X chromosome behaves differently: a female has two X chromosomes, so a faulty gene on one X can be masked by a normal copy on the other, whereas a male has only one X, so any faulty gene on it is expressed with nothing to mask it. That asymmetry is the entire reason X-linked patterns look so different from autosomal ones on a pedigree, and it is worth sitting with that idea before moving to the four named patterns.
Autosomal dominant (AD): only one faulty copy of the gene, out of the two a person carries, is enough to cause disease. The pedigree shows a vertical pattern: the condition appears in every generation, roughly half of each affected parent's children are affected, both sexes are affected equally, and male-to-male transmission is possible. For example, consider Huntington's disease: a single faulty copy of the HTT gene, inherited from either parent, is sufficient on its own to cause the condition later in life.
Autosomal recessive (AR): two faulty copies, one from each parent, are needed. Two unaffected CARRIER parents (people with one faulty and one normal copy, and therefore no symptoms) can have an affected child. The pedigree often skips a generation, both sexes are affected equally, and CONSANGUINITY (parents who are blood relatives, sharing more genes than an unrelated couple) raises the risk because it raises the chance both parents carry the same faulty gene.
X-linked recessive (XLR): the faulty gene sits on the X chromosome, and one faulty copy is enough to cause disease in a male, because he has no second X to mask it. Females need two faulty copies to be affected, so they are usually unaffected carriers. The single most useful clue is that there is never father-to-son transmission, because a father passes his Y chromosome, not his X, to a son. An affected father, though, makes every one of his daughters an obligate carrier, since each daughter must receive his one X chromosome.
Mitochondrial inheritance: MITOCHONDRIAL DNA (a small separate ring of DNA carried only inside mitochondria, the cell's energy-producing structures) is inherited only from the mother, because sperm mitochondria are destroyed after fertilisation. An affected mother passes the condition to all her children, of either sex, while an affected father passes it to none of his children. This maternal-only transmission is the pattern's unmistakable fingerprint.
Autosomal dominant versus autosomal recessive is mostly a matter of generation gaps and risk: AD runs through every generation with roughly 50% offspring risk, while AR can skip generations entirely and carries roughly 25% risk between two carrier parents. X-linked recessive versus autosomal dominant is settled by sex ratio and by father-to-son transmission: X-linked recessive clusters in males with no father-to-son link, whereas autosomal dominant affects both sexes and allows that link freely. Mitochondrial inheritance is told apart from all three nuclear patterns by one feature alone: it only ever passes through the mother, regardless of the sex of the child.
A suspected inheritance pattern is a clinical hypothesis drawn from the pedigree, and it is then confirmed with molecular genetic testing, most often targeted gene sequencing or a next-generation sequencing panel that reads the specific gene implicated by the family history. Genetic counsellors use the American College of Medical Genetics and Genomics (ACMG) framework to classify a given DNA variant as pathogenic, likely pathogenic, uncertain, likely benign, or benign, which determines how confidently a family can be told the result applies to them.
There is no way to alter an inheritance pattern itself, so the practical work is GENETIC COUNSELLING (a structured conversation covering the risk to future children, the options for testing, and the emotional impact of the result) plus, where relevant, presymptomatic testing for at-risk relatives with formal psychological support built in, as recommended for conditions like Huntington's disease. Prenatal options such as chorionic villus sampling or amniocentesis, and reproductive options such as preimplantation genetic testing during IVF, are discussed by specialist clinical genetics services once a pattern and a specific causative gene variant are both confirmed. Source-wise, variant interpretation is grounded in ACMG/AMP standards, while patient-facing management is delivered through specialist clinical genetics services; this is not a NICE, DSM-5, or ICD-11 treatment guideline topic because an inheritance pattern itself is not a disorder to medicate. The practical management plan is risk communication, cascade testing of relatives when appropriate, reproductive counselling, and condition-specific treatment or surveillance only after the actual disease and variant are known.
When a pedigree question stalls you, do not scan for a familiar disease name first. Scan for father-to-son transmission first: its presence rules out X-linked recessive immediately, and its absence combined with affected females should push you straight toward autosomal or X-linked recessive rather than X-linked dominant.
Read a pedigree by asking two questions, which sexes are affected, and does an affected father ever have an affected son, and the inheritance pattern nearly names itself.