Genetic conditions are disorders caused by mutations in one or more genes or by abnormalities in chromosomes. In contrast, congenital disorders are not always genetic in origin. They may result from complications during embryonic or fetal development or from issues that occur during the birth process. An example of a non-genetic congenital disorder is fetal alcohol syndrome, which arises from maternal alcohol consumption during pregnancy. This condition can lead to a range of birth defects, including distinctive facial features and intellectual impairment.
Most variations in DNA do not cause disease and are known as polymorphisms. A mutation occurs when a change in DNA results in a protein that functions improperly or fails to function altogether. Interestingly, the same genetic mutation may produce different physical outcomes in different individuals, a phenomenon known as gene expression.
Genes exist in alternative forms called alleles, which occupy specific positions (loci) on chromosomes. Each individual inherits one allele from each parent at every locus. For autosomal genes, the genotype refers to the pair of alleles present at a specific locus on homologous chromosomes.
The phenotype is the observable expression of a genotype. It may be morphological, clinical, biochemical, or molecular, and can be identified through physical examination or laboratory testing of blood or tissues. Phenotypes can be qualitative or quantitative, such as the presence or absence of a disease, body mass index, or blood glucose levels. While phenotypes may be normal or abnormal, the focus here is on disease-related phenotypes associated with genetic abnormalities.
Common Genetic Diseases: Gene Defects, Inheritance & Phenotypic Features
| Disease | Gene / Defect | Inheritance | Phenotypic Features |
|---|---|---|---|
| Abacavir-Induced Stevens–Johnson Syndrome / Toxic Epidermal Necrolysis | HLA-B*5701 allele (~50% risk in carriers) | Autosomal Dominant | Severe red/purple skin and mucosal lesions (eyes, mouth, genitalia) appearing 10–14 days after abacavir therapy |
| Achondroplasia | FGFR3 mutation (1138G>A ~98%, 1138G>C 1–2%) | Autosomal Dominant | Prenatal onset, short limbs, large head, spinal cord compression |
| Age-Related Macular Degeneration | CFH gene variant (Tyr402His) | Multifactorial | Central vision loss, drusen, retinal pigment changes, neovascularization (>50 years) |
| Alzheimer Disease | APP, PSEN1, PSEN2 mutations | Multifactorial / Autosomal Dominant | Dementia, β-amyloid plaques, neurofibrillary tangles, amyloid angiopathy |
| Autism / 16p11.2 Deletion Syndrome | Chromosome 16p11.2 microdeletion | Autosomal Dominant / De Novo | Early onset, impaired social interaction, communication deficits, variable intelligence |
| Beckwith–Wiedemann Syndrome | Imprinting defects (11p15 region) | Chromosomal | Overgrowth, macroglossia, omphalocele, organ enlargement, tumor risk |
| Hereditary Breast & Ovarian Cancer | BRCA1 / BRCA2 mutations | Autosomal Dominant | Increased risk of breast, ovarian, prostate cancers |
| Charcot–Marie–Tooth Disease Type 1A | PMP22 mutation/duplication | Autosomal Dominant | Progressive distal muscle weakness, wasting, reduced reflexes |
| CHARGE Syndrome | CHD7 mutation | Autosomal Dominant | Eye coloboma, heart defects, choanal atresia, growth delay, ear anomalies |
| Chronic Myelogenous Leukemia | BCR-ABL1 fusion gene | Somatic Mutation | Leukocytosis, splenomegaly, fatigue |
| Crohn Disease | NOD2 mutations | Multifactorial | Abdominal pain, diarrhea, fistulas, granulomas, extraintestinal symptoms |
| Cystic Fibrosis | CFTR mutation | Autosomal Recessive | Lung disease, pancreatic insufficiency, infertility, high sweat chloride |
| Nonsyndromic Deafness | GJB2 mutation | Autosomal Dominant/Recessive | Congenital or progressive hearing loss |
| Duchenne Muscular Dystrophy | DMD mutation | X-linked | Muscle weakness, calf enlargement, elevated CK |
| Familial Adenomatous Polyposis | APC mutation | Autosomal Dominant | Multiple colon polyps, high colorectal cancer risk |
| Familial Hypercholesterolemia | LDLR mutation | Autosomal Dominant | High cholesterol, atherosclerosis, xanthomas |
| Fragile X Syndrome | FMR1 CGG expansion (>200 repeats) | X-linked | Intellectual disability, dysmorphic face, large testes |
| Gaucher Disease Type I | GBA1 mutation | Autosomal Recessive | Enlarged liver/spleen, anemia, bone pain |
| G6PD Deficiency | G6PD mutation | X-linked | Hemolytic anemia, neonatal jaundice |
| Hereditary Hemochromatosis | HFE mutation | Autosomal Recessive | Iron overload, fatigue, diabetes, cirrhosis |
| Hemophilia | F8 / F9 mutation | X-linked | Bleeding tendency, joint bleeding, hematomas |
| Hirschsprung Disease | RET, EDNRB, EDN3, GDNF | Mixed inheritance | Constipation, abdominal distension, enterocolitis |
| Holoprosencephaly | SHH mutation | Autosomal Dominant | Brain malformation, facial abnormalities |
| Huntington Disease | HTT CAG repeat expansion | Autosomal Dominant | Movement disorder, cognitive decline, psychiatric issues |
| Hypertrophic Cardiomyopathy | Sarcomere gene mutations | Autosomal Dominant | Thickened heart muscle, arrhythmias, sudden death |
| Type 1 Diabetes Mellitus | Autoimmune β-cell destruction | Multifactorial | Hyperglycemia, polyuria, ketosis |
| Intrauterine Growth Restriction | Chromosomal deletion | Chromosomal | Poor fetal growth, dysmorphic features |
| Long QT Syndrome | Ion channel gene mutations | Autosomal Dominant/Recessive | Arrhythmias, syncope, sudden death |
| Lynch Syndrome | DNA mismatch repair genes | Autosomal Dominant | Colorectal and multiple cancers |
| Marfan Syndrome | FBN1 mutation | Autosomal Dominant | Tall stature, lens dislocation, aortic aneurysm |
| MCAD Deficiency | ACADM mutation | Autosomal Recessive | Hypoglycemia, lethargy, liver dysfunction |
| Miller–Dieker Syndrome | 17p13.3 deletion | Chromosomal | Lissencephaly, severe developmental delay |
| MERRF Syndrome | mtDNA (tRNAlys mutation) | Mitochondrial | Seizures, muscle weakness, dementia |
| Neurofibromatosis Type 1 | NF1 mutation | Autosomal Dominant | Café-au-lait spots, neurofibromas, optic tumors |
| Type 2 Diabetes Mellitus | Insulin resistance + deficiency | Multifactorial | Hyperglycemia, obesity, acanthosis nigricans |
| Ornithine Transcarbamylase Deficiency | OTC mutation | X-linked | Hyperammonemia, coma |
| Polycystic Kidney Disease | PKD1 / PKD2 mutation | Autosomal Dominant | Kidney cysts, renal failure, aneurysms |
| Prader–Willi Syndrome | Loss of paternal 15q11–q13 | Chromosomal | Hypotonia, obesity, cognitive impairment |
| Retinoblastoma | RB1 mutation | Autosomal Dominant | Leukocoria, vision loss |
| Rett Syndrome | MECP2 mutation | X-linked Dominant | Neurodevelopmental regression, hand stereotypies |
| Sex Development Disorder (46,XX male) | SRY translocation | Y-linked / Chromosomal | Infertility, mismatch of genotype and phenotype |
| Sickle Cell Disease | β-globin mutation (Glu6Val) | Autosomal Recessive | Anemia, vaso-occlusion, organ damage |
| Tay–Sachs Disease | HEXA mutation | Autosomal Recessive | Neurodegeneration, cherry-red macula |
| Thalassemia | α or β globin deficiency | Autosomal Recessive | Microcytic anemia, hepatosplenomegaly |
| TPMT Deficiency | TPMT polymorphism | Autosomal Semidominant | Drug toxicity, myelosuppression |
| Thrombophilia (Factor V Leiden) | FV / PROC mutation | Autosomal Dominant | Increased risk of blood clots |
| Turner Syndrome | Monosomy X | Chromosomal | Short stature, ovarian failure |
| Xeroderma Pigmentosum | DNA repair defect | Autosomal Recessive | UV sensitivity, skin cancer |