Genetics Reference
High-yield reference for genetic disorders and inheritance patterns.
Huntington Disease
Autosomal DominantHTT (CAG trinucleotide repeat)
4p16.3
Clinical Features
- Chorea (involuntary movements)
- Athetosis
- Progressive dementia and behavioral changes
- Anticipation (earlier onset in subsequent generations)
- Caudate nucleus atrophy
Marfan Syndrome
Autosomal DominantFBN1 (Fibrillin-1)
15q21.1
Clinical Features
- Tall stature with long extremities (arachnodactyly)
- Pectus excavatum or carinatum
- Ectopia lentis (upward and outward subluxation)
- Aortic root dilation, risk of dissection
- Mitral valve prolapse
Neurofibromatosis Type 1 (von Recklinghausen)
Autosomal DominantNF1 (Neurofibromin, a tumor suppressor)
17q11.2
Clinical Features
- Café-au-lait spots (≥6)
- Cutaneous neurofibromas
- Lisch nodules (pigmented iris hamartomas)
- Optic gliomas
- Freckling in axillary or inguinal regions
Neurofibromatosis Type 2
Autosomal DominantNF2 (Merlin)
22q12.2
Clinical Features
- Bilateral vestibular schwannomas (acoustic neuromas)
- Meningiomas
- Ependymomas
- Juvenile cataracts
Achondroplasia
Autosomal DominantFGFR3 (Gain of function)
4p16.3
Clinical Features
- Most common cause of dwarfism
- Short limbs (rhizomelic shortening) with normal torso
- Macrocephaly with frontal bossing
- Midface hypoplasia
- 80% occur as sporadic new mutations (associated with advanced paternal age)
Familial Hypercholesterolemia (Type IIa)
Autosomal DominantLDLR (LDL receptor defect)
19p13.2
Clinical Features
- Severely elevated LDL cholesterol
- Tendon xanthomas (especially Achilles)
- Corneal arcus before age 45
- Premature atherosclerosis and myocardial infarction
Osteogenesis Imperfecta
Autosomal DominantCOL1A1 or COL1A2 (Type I collagen defect)
17q21.33 / 7q21.3
Clinical Features
- Multiple frequent bone fractures
- Blue sclerae
- Hearing loss (ossicle fracture/fixation)
- Dental imperfections (dentinogenesis imperfecta)
Cystic Fibrosis
Autosomal RecessiveCFTR (ΔF508 most common)
7q31.2
Clinical Features
- Thick, sticky mucus production
- Recurrent pulmonary infections (Pseudomonas, S. aureus)
- Pancreatic insufficiency and malabsorption
- Meconium ileus in newborns
- Infertility in males (absence of vas deferens)
Sickle Cell Anemia
Autosomal RecessiveHBB (Glutamic acid to Valine substitution)
11p15.4
Clinical Features
- Vaso-occlusive crises (painful crises, dactylitis)
- Hemolytic anemia
- Splenic sequestration and autosplenectomy
- Increased risk of encapsulated bacterial infections
- Acute chest syndrome
Phenylketonuria (PKU)
Autosomal RecessivePAH (Phenylalanine hydroxylase deficiency)
12q23.2
Clinical Features
- Intellectual disability (if untreated)
- Musty body odor
- Fair skin and hair (decreased melanin)
- Seizures
- Requires phenylalanine-restricted diet
Tay-Sachs Disease
Autosomal RecessiveHEXA (Hexosaminidase A deficiency)
15q23
Clinical Features
- Progressive neurodegeneration
- Cherry-red spot on macula
- Lysosomes with onion skin appearance
- No hepatosplenomegaly (unlike Niemann-Pick)
- Exaggerated startle response
Niemann-Pick Disease (Type A/B)
Autosomal RecessiveSMPD1 (Sphingomyelinase deficiency)
11p15.4
Clinical Features
- Progressive neurodegeneration
- Cherry-red spot on macula
- Hepatosplenomegaly
- Foam cells (lipid-laden macrophages)
Gaucher Disease
Autosomal RecessiveGBA (Glucocerebrosidase deficiency)
1q22
Clinical Features
- Most common lysosomal storage disease
- Hepatosplenomegaly
- Pancytopenia
- Osteoporosis and bone crises (Erlenmeyer flask deformity)
- Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper)
Wilson Disease
Autosomal RecessiveATP7B (Copper transport defect)
13q14.3
Clinical Features
- Copper accumulation in liver (cirrhosis)
- Copper accumulation in brain (parkinsonism, psychiatric symptoms)
- Kayser-Fleischer rings in the cornea
- Decreased serum ceruloplasmin
Hemophilia A
X-linked RecessiveF8 (Factor VIII deficiency)
Xq28
Clinical Features
- Hemarthrosis (bleeding into joints)
- Prolonged PTT, normal PT/Bleeding time
- Easy bruising and bleeding
- Primarily affects males
Hemophilia B (Christmas Disease)
X-linked RecessiveF9 (Factor IX deficiency)
Xq27.1
Clinical Features
- Clinically indistinguishable from Hemophilia A
- Hemarthrosis, prolonged PTT
- Treated with Factor IX replacement
Duchenne Muscular Dystrophy
X-linked RecessiveDMD (Frameshift mutation, truncated dystrophin)
Xp21.2
Clinical Features
- Progressive myofiber damage
- Weakness begins in pelvic girdle and ascends
- Pseudohypertrophy of calf muscles
- Gowers sign
- Dilated cardiomyopathy is common cause of death
Lesch-Nyhan Syndrome
X-linked RecessiveHPRT1 (HGPRT deficiency)
Xq26.2
Clinical Features
- Defective purine salvage pathway (excess uric acid)
- Hyperuricemia and gout
- Self-mutilation (biting lips/fingers)
- Intellectual disability
- Choreoathetosis
Fragile X Syndrome
X-linked DominantFMR1 (CGG trinucleotide repeat)
Xq27.3
Clinical Features
- Most common inherited cause of intellectual disability
- Long face with large jaw and large everted ears
- Macroorchidism (large testes)
- Autism spectrum behaviors
- Mitral valve prolapse
Down Syndrome (Trisomy 21)
ChromosomalN/A
21 (Three copies)
Clinical Features
- Intellectual disability
- Flat facial profile, prominent epicanthal folds
- Single palmar crease
- Congenital heart defects (Atrioventricular septal defect)
- Increased risk of early-onset Alzheimer's and ALL/AML
Edwards Syndrome (Trisomy 18)
ChromosomalN/A
18 (Three copies)
Clinical Features
- Severe intellectual disability
- Rocker-bottom feet
- Micrognathia (small jaw)
- Clenched hands with overlapping fingers
- Prominent occiput
- High mortality within first year
Patau Syndrome (Trisomy 13)
ChromosomalN/A
13 (Three copies)
Clinical Features
- Severe intellectual disability
- Microphthalmia (small eyes)
- Cleft lip and palate
- Holoprosencephaly
- Polydactyly
- High mortality within first year
Turner Syndrome
ChromosomalN/A
45, X
Clinical Features
- Short stature
- Webbed neck (cystic hygroma)
- Streak ovaries (primary amenorrhea, premature ovarian failure)
- Bicuspid aortic valve and coarctation of the aorta
- Normal intelligence
Klinefelter Syndrome
ChromosomalN/A
47, XXY
Clinical Features
- Tall stature with disproportionately long limbs
- Testicular atrophy and infertility
- Gynecomastia
- Female hair distribution
- Presence of inactivated X chromosome (Barr body)
Cri-du-chat Syndrome
ChromosomalN/A
5p- (Microdeletion of short arm of chromosome 5)
Clinical Features
- High-pitched crying/meowing
- Microcephaly
- Severe intellectual disability
- Epicanthal folds
- Cardiac abnormalities (VSD)
DiGeorge Syndrome (22q11.2 Deletion)
ChromosomalN/A
22q11.2 (Microdeletion)
Clinical Features
- Cleft palate
- Abnormal facies
- Thymic aplasia (T-cell deficiency)
- Cardiac defects (Tetralogy of Fallot, truncus arteriosus)
- Hypocalcemia (parathyroid aplasia)
Alkaptonuria
Autosomal RecessiveHGD
3q13.33
Clinical Features
- Urine turns black on standing
- Ochronosis (dark connective tissue)
- Severe early-onset osteoarthritis
Homocystinuria
Autosomal RecessiveCBS
21q22.3
Clinical Features
- Marfanoid habitus
- Downward lens subluxation
- Hypercoagulability and thrombosis
- Intellectual disability
Maple Syrup Urine Disease
Autosomal RecessiveBCKDHA/B
19q13.2
Clinical Features
- Urine smells like maple syrup
- Severe CNS defects
- Vomiting and lethargy in infants
- Blocked degradation of branched amino acids (I, L, V)
Galactosemia
Autosomal RecessiveGALT
9p13.3
Clinical Features
- Infantile cataracts
- Failure to thrive
- Jaundice, hepatomegaly
- E. coli sepsis
Von Gierke Disease (Type I)
Autosomal RecessiveG6PC
17q21.31
Clinical Features
- Severe fasting hypoglycemia
- Massive hepatomegaly
- Increased blood lactate
- Gout
Pompe Disease (Type II)
Autosomal RecessiveGAA
17q25.3
Clinical Features
- Cardiomegaly
- Hypertrophic cardiomyopathy
- Exercise intolerance
- Early death
Cori Disease (Type III)
Autosomal RecessiveAGL
1p21.2
Clinical Features
- Milder form of Von Gierke
- Normal blood lactate levels
- Accumulation of limit dextrin-like structures in cytosol
McArdle Disease (Type V)
Autosomal RecessivePYGM
11q13.1
Clinical Features
- Muscle cramps during exercise
- Myoglobinuria (red urine) after exercise
- Second wind phenomenon
- Normal life expectancy
Fabry Disease
X-linked RecessiveGLA
Xq22.1
Clinical Features
- Episodic peripheral neuropathy
- Angiokeratomas
- Hypohidrosis
- Progressive renal failure
- Cardiovascular disease
Krabbe Disease
Autosomal RecessiveGALC
14q31.3
Clinical Features
- Peripheral neuropathy
- Developmental delay
- Optic atrophy
- Globoid cells
Metachromatic Leukodystrophy
Autosomal RecessiveARSA
22q13.33
Clinical Features
- Central and peripheral demyelination
- Ataxia
- Dementia
Hurler Syndrome
Autosomal RecessiveIDUA
4p16.3
Clinical Features
- Developmental delay
- Gargoylism
- Airway obstruction
- Corneal clouding
- Hepatosplenomegaly
Hunter Syndrome
X-linked RecessiveIDS
Xq28
Clinical Features
- Mild Hurler + aggressive behavior
- No corneal clouding
Friedreich Ataxia
Autosomal RecessiveFXN (GAA repeat)
9q21.11
Clinical Features
- Staggering gait
- Frequent falling
- Nystagmus
- Pes cavus, hammer toes
- Hypertrophic cardiomyopathy
Myotonic Dystrophy Type 1
Autosomal DominantDMPK (CTG repeat)
19q13.32
Clinical Features
- Myotonia (delayed muscle relaxation)
- Muscle wasting
- Cataracts
- Testicular atrophy
- Frontal balding
- Arrhythmias
Prader-Willi Syndrome
ChromosomalImprinting defect (Maternal uniparental disomy)
15q11-q13
Clinical Features
- Hyperphagia
- Obesity
- Intellectual disability
- Hypogonadism
- Hypotonia
Angelman Syndrome
ChromosomalUBE3A (Paternal uniparental disomy)
15q11-q13
Clinical Features
- Inappropriate laughter (happy puppet)
- Seizures
- Ataxia
- Severe intellectual disability
Williams Syndrome
ChromosomalMicrodeletion
7q11.23
Clinical Features
- Elfin facies
- Extreme friendliness with strangers
- Hypercalcemia (increased sensitivity to vitamin D)
- Supravalvular aortic stenosis
Wiskott-Aldrich Syndrome
X-linked RecessiveWAS
Xp11.23
Clinical Features
- WATER: Wiskott-Aldrich, Thrombocytopenia, Eczema, Recurrent infections
- Increased risk of autoimmune disease and malignancy
Bruton Agammaglobulinemia
X-linked RecessiveBTK
Xq22.1
Clinical Features
- Recurrent bacterial and enteroviral infections after 6 months
- Absent B cells in peripheral blood
- Decreased Ig of all classes
- Absent/scanty lymph nodes and tonsils
Severe Combined Immunodeficiency (SCID)
Autosomal RecessiveIL2RG or ADA
Xq13.1 / 20q13.12
Clinical Features
- Failure to thrive
- Chronic diarrhea
- Thrush
- Recurrent viral, bacterial, fungal, and protozoal infections
- Absence of thymic shadow
Ataxia-Telangiectasia
Autosomal RecessiveATM
11q22.3
Clinical Features
- Cerebellar ataxia
- Telangiectasias (spider angiomas)
- IgA deficiency
- Increased risk of lymphoma and leukemia
Chediak-Higashi Syndrome
Autosomal RecessiveLYST
1q42.3
Clinical Features
- Progressive neurodegeneration
- Oculocutaneous albinism
- Recurrent pyogenic infections
- Peripheral neuropathy
- Giant granules in granulocytes
Chronic Granulomatous Disease
X-linked RecessiveCYBB
Xp21.1
Clinical Features
- Defect in NADPH oxidase
- Increased susceptibility to catalase-positive organisms (S. aureus, Aspergillus, Nocardia, Serratia)
Familial Adenomatous Polyposis (FAP)
Autosomal DominantAPC
5q22.2
Clinical Features
- Thousands of colonic polyps arise after puberty
- 100% progress to colorectal cancer unless colon is resected
- Always involves the rectum
Lynch Syndrome (HNPCC)
Autosomal DominantMLH1, MSH2 (Mismatch repair)
3p22.2 / 2p21
Clinical Features
- High risk of colorectal, endometrial, and ovarian cancer
- Colorectal cancer arises de novo (not from polyps) at an early age
Li-Fraumeni Syndrome
Autosomal DominantTP53
17p13.1
Clinical Features
- Multiple malignancies at an early age
- SBLA syndrome: Sarcoma, Breast, Leukemia, Adrenal gland
Multiple Endocrine Neoplasia Type 1 (MEN 1)
Autosomal DominantMEN1
11q13
Clinical Features
- 3 Ps: Pituitary tumors, Parathyroid adenomas, Pancreatic endocrine tumors (e.g., Zollinger-Ellison)
Multiple Endocrine Neoplasia Type 2A (MEN 2A)
Autosomal DominantRET
10q11.21
Clinical Features
- Parathyroid hyperplasia
- Medullary thyroid carcinoma
- Pheochromocytoma
Multiple Endocrine Neoplasia Type 2B (MEN 2B)
Autosomal DominantRET
10q11.21
Clinical Features
- Medullary thyroid carcinoma
- Pheochromocytoma
- Mucosal neuromas (oral/intestinal ganglioneuromatosis)
- Marfanoid habitus
Peutz-Jeghers Syndrome
Autosomal DominantSTK11
19p13.3
Clinical Features
- Multiple hamartomatous polyps in GI tract
- Hyperpigmented macules on lips, oral mucosa, and genitalia
- Increased risk of breast and GI cancers
Tuberous Sclerosis
Autosomal DominantTSC1 / TSC2
9q34 / 16p13.3
Clinical Features
- Hamartomas in CNS and skin
- Angiofibromas
- Mitral regurgitation
- Ash-leaf spots
- Cardiac rhabdomyoma
- Autosomal dominant
- Intellectual disability
- Renal angiomyolipoma
- Seizures
Von Hippel-Lindau Disease
Autosomal DominantVHL
3p25.3
Clinical Features
- Hemangioblastomas (retina, brain stem, cerebellum, spine)
- Angiomatosis
- Bilateral renal cell carcinomas
- Pheochromocytomas
Polycystic Kidney Disease (ADPKD)
Autosomal DominantPKD1 / PKD2
16p13.3 / 4q22.1
Clinical Features
- Bilateral massive enlargement of kidneys due to multiple large cysts
- Flank pain, hematuria, hypertension
- Associated with berry aneurysms and mitral valve prolapse
Hereditary Spherocytosis
Autosomal DominantSPTA1, SPTB, ANK1
Multiple
Clinical Features
- Defect in RBC cytoskeleton-membrane tethering proteins
- Extravascular hemolysis in spleen
- Splenomegaly, jaundice
- Increased mean corpuscular hemoglobin concentration (MCHC)
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
X-linked RecessiveG6PD
Xq28
Clinical Features
- Episodic hemolytic anemia following oxidative stress (e.g., sulfa drugs, antimalarials, fava beans)
- Heinz bodies and bite cells on blood smear
Thalassemia (Alpha)
Autosomal RecessiveHBA1 / HBA2
16p13.3
Clinical Features
- Microcytic, hypochromic anemia
- Target cells
- Hb Barts (hydrops fetalis) if all 4 alleles deleted
Thalassemia (Beta)
Autosomal RecessiveHBB
11p15.4
Clinical Features
- Microcytic, hypochromic anemia
- Target cells
- Crew cut on skull x-ray (marrow expansion)
- Chipmunk facies
- Requires lifelong blood transfusions
Ehlers-Danlos Syndrome (Classical)
Autosomal DominantCOL5A1 / COL5A2
Multiple
Clinical Features
- Hyperextensible skin
- Hypermobile joints
- Easy bruising
- Defective Type V collagen
Ehlers-Danlos Syndrome (Vascular)
Autosomal DominantCOL3A1
2q32.2
Clinical Features
- Fragile tissues
- Prone to spontaneous rupture of arteries (e.g., aorta) and organs (e.g., intestines, uterus)
- Defective Type III collagen