Common Genetic Disorders with Diagnostic Findings

This is a comprehensive list of genetic disorders, complete with specific diagnostic criteria, tailored for students and medical professionals. Each disorder is described in detail, including its genetic basis, clinical presentation, and the diagnostic tests required for confirmation. This resource simplifies the complex world of genetics, making it more accessible to those in the medical field, whether they are studying or practicing.

Designed to support both learning and clinical practice, this list offers a focused approach to understanding genetic conditions. It provides healthcare providers with a reliable reference for recognizing and diagnosing genetic disorders, ensuring that key diagnostic steps are easily understood and applied in clinical settings.

1. Down Syndrome

• Genetic defect: Trisomy 21
• Diagnostic findings:
  • Flat facial profile
  • Upward slanting eyes
  • Small ears
  • Single palmar crease
  • Hypotonia
  • Cognitive delays

2. Cystic Fibrosis

• Genetic defect: Mutations in CFTR gene
• Diagnostic findings:
  • Recurrent respiratory infections
  • Pancreatic insufficiency
  • Elevated sweat chloride levels
  • Failure to thrive
  • Male infertility

3. Sickle Cell Disease

• Genetic defect: Mutations in HBB gene
• Diagnostic findings:
  • Hemolytic anemia
  • Vaso-occlusive pain crises
  • Splenic sequestration
  • Acute chest syndrome
  • Delayed growth and puberty

4. Huntington's Disease

• Genetic defect: CAG repeat expansion in HTT gene
• Diagnostic findings:
  • Progressive motor dysfunction
  • Cognitive decline
  • Psychiatric symptoms
  • Chorea
  • Family history of similar symptoms

5. Duchenne Muscular Dystrophy

• Genetic defect: Mutations in DMD gene
• Diagnostic findings:
  • Progressive muscle weakness
  • Gower's sign
  • Calf pseudohypertrophy
  • Elevated creatine kinase levels
  • Cardiomyopathy

6. Phenylketonuria (PKU)

• Genetic defect: Mutations in PAH gene
• Diagnostic findings:
  • Elevated phenylalanine levels in blood
  • Intellectual disability (if untreated)
  • Eczema
  • Musty odor
  • Seizures

7. Marfan Syndrome

• Genetic defect: Mutations in FBN1 gene
• Diagnostic findings:
  • Tall stature
  • Long limbs and fingers (arachnodactyly)
  • Lens dislocation
  • Aortic root dilation
  • Joint hypermobility

8. Fragile X Syndrome

• Genetic defect: CGG repeat expansion in FMR1 gene
• Diagnostic findings:
  • Intellectual disability
  • Autism spectrum features
  • Large ears
  • Long face
  • Macroorchidism in males

9. Neurofibromatosis Type 1

• Genetic defect: Mutations in NF1 gene
• Diagnostic findings:
  • Café-au-lait spots
  • Axillary or inguinal freckling
  • Lisch nodules
  • Neurofibromas
  • Optic glioma

10. Turner Syndrome

• Genetic defect: Monosomy X (45,X)
• Diagnostic findings:
  • Short stature
  • Primary amenorrhea
  • Webbed neck
  • Shield chest
  • Cardiovascular abnormalities

11. Klinefelter Syndrome

• Genetic defect: 47,XXY karyotype
• Diagnostic findings:
  • Tall stature
  • Small testes
  • Gynecomastia
  • Infertility
  • Learning difficulties

12. Prader-Willi Syndrome

• Genetic defect: Paternal deletion or maternal uniparental disomy of 15q11-q13
• Diagnostic findings:
  • Hypotonia in infancy
  • Hyperphagia and obesity
  • Short stature
  • Developmental delays
  • Hypogonadism

13. Angelman Syndrome

• Genetic defect: Maternal deletion or paternal uniparental disomy of 15q11-q13
• Diagnostic findings:
  • Severe developmental delay
  • Speech impairment
  • Ataxia
  • Seizures
  • Happy demeanor with frequent laughter

14. Tay-Sachs Disease

• Genetic defect: Mutations in HEXA gene
• Diagnostic findings:
  • Progressive neurodegeneration
  • Cherry-red spot on macula
  • Seizures
  • Hypotonia
  • Developmental regression

15. Hemophilia A

• Genetic defect: Mutations in F8 gene
• Diagnostic findings:
  • Prolonged bleeding
  • Easy bruising
  • Hemarthrosis
  • Decreased factor VIII activity
  • Family history of bleeding disorders

16. Rett Syndrome

• Genetic defect: Mutations in MECP2 gene
• Diagnostic findings:
  • Normal early development followed by regression
  • Loss of purposeful hand movements
  • Stereotypic hand movements
  • Acquired microcephaly
  • Breathing abnormalities

17. Wilson's Disease

• Genetic defect: Mutations in ATP7B gene
• Diagnostic findings:
  • Hepatic dysfunction
  • Kayser-Fleischer rings
  • Neurological symptoms
  • Low serum ceruloplasmin
  • Elevated urinary copper excretion

18. Fabry Disease

• Genetic defect: Mutations in GLA gene
• Diagnostic findings:
  • Acroparesthesias
  • Angiokeratomas
  • Corneal verticillata
  • Renal insufficiency
  • Cardiomyopathy

19. DiGeorge Syndrome

• Genetic defect: 22q11.2 deletion
• Diagnostic findings:
  • Congenital heart defects
  • Palatal abnormalities
  • Immunodeficiency
  • Hypocalcemia
  • Characteristic facial features

20. Gaucher Disease

• Genetic defect: Mutations in GBA gene
• Diagnostic findings:
  • Hepatosplenomegaly
  • Thrombocytopenia
  • Bone pain and fractures
  • Low glucocerebrosidase enzyme activity
  • Gaucher cells in bone marrow

21. Albinism

• Genetic defect: Mutations in various genes (e.g., TYR, OCA2)
• Diagnostic findings:
  • Lack of pigmentation in skin, hair, and eyes
  • Photophobia
  • Nystagmus
  • Visual impairment
  • Increased risk of skin cancer

22. Alport Syndrome

• Genetic defect: Mutations in COL4A3, COL4A4, or COL4A5 genes
• Diagnostic findings:
  • Progressive kidney disease
  • Sensorineural hearing loss
  • Ocular abnormalities
  • Hematuria
  • Proteinuria

23. Ehlers-Danlos Syndrome

• Genetic defect: Mutations in various genes (e.g., COL5A1, COL5A2)
• Diagnostic findings:
  • Joint hypermobility
  • Skin hyperextensibility
  • Tissue fragility
  • Easy bruising
  • Chronic joint pain

24. Friedreich's Ataxia

• Genetic defect: GAA repeat expansion in FXN gene
• Diagnostic findings:
  • Progressive ataxia
  • Loss of deep tendon reflexes
  • Cardiomyopathy
  • Scoliosis
  • Diabetes mellitus

25. Maple Syrup Urine Disease

• Genetic defect: Mutations in BCKDHA, BCKDHB, or DBT genes
• Diagnostic findings:
  • Sweet-smelling urine
  • Poor feeding
  • Vomiting
  • Lethargy
  • Neurological deterioration

26. Noonan Syndrome

• Genetic defect: Mutations in various genes (e.g., PTPN11, SOS1)
• Diagnostic findings:
  • Short stature
  • Distinctive facial features
  • Congenital heart defects
  • Webbed neck
  • Developmental delays

27. Osteogenesis Imperfecta

• Genetic defect: Mutations in COL1A1 or COL1A2 genes
• Diagnostic findings:
  • Frequent fractures
  • Blue sclerae
  • Dentinogenesis imperfecta
  • Short stature
  • Hearing loss

28. Polycystic Kidney Disease

• Genetic defect: Mutations in PKD1 or PKD2 genes
• Diagnostic findings:
  • Multiple renal cysts
  • Hypertension
  • Flank pain
  • Hematuria
  • Liver cysts

29. Familial Hypercholesterolemia

• Genetic defect: Mutations in LDLR, APOB, or PCSK9 genes
• Diagnostic findings:
  • Elevated LDL cholesterol
  • Xanthomas
  • Premature cardiovascular disease
  • Arcus cornealis
  • Family history of high cholesterol

30. Spinal Muscular Atrophy

• Genetic defect: Homozygous deletion or mutation of SMN1 gene
• Diagnostic findings:
  • Progressive muscle weakness
  • Hypotonia
  • Areflexia
  • Respiratory difficulties
  • Tongue fasciculations

31. Hemochromatosis

• Genetic defect: Mutations in HFE gene
• Diagnostic findings:
  • Elevated serum ferritin and transferrin saturation
  • Liver dysfunction
  • Skin hyperpigmentation
  • Diabetes mellitus
  • Arthropathy

32. Mucopolysaccharidosis Type I (Hurler Syndrome)

• Genetic defect: Mutations in IDUA gene
• Diagnostic findings:
  • Coarse facial features
  • Hepatosplenomegaly
  • Skeletal abnormalities
  • Corneal clouding
  • Developmental delay

33. Biotinidase Deficiency

• Genetic defect: Mutations in BTD gene
• Diagnostic findings:
  • Seizures
  • Hypotonia
  • Developmental delay
  • Alopecia
  • Skin rash

34. Galactosemia

• Genetic defect: Mutations in GALT gene
• Diagnostic findings:
  • Failure to thrive
  • Vomiting
  • Jaundice
  • Cataracts
  • Escherichia coli sepsis

35. Achondroplasia

• Genetic defect: Mutations in FGFR3 gene
• Diagnostic findings:
  • Short-limbed dwarfism
  • Macrocephaly
  • Midface hypoplasia
  • Trident hand
  • Lumbar lordosis

36. Alpha-1 Antitrypsin Deficiency

• Genetic defect: Mutations in SERPINA1 gene
• Diagnostic findings:
  • Emphysema
  • Liver disease
  • Low serum alpha-1 antitrypsin levels
  • Bronchiectasis
  • Panniculitis

37. Androgen Insensitivity Syndrome

• Genetic defect: Mutations in AR gene
• Diagnostic findings:
  • 46,XY karyotype with female phenotype
  • Primary amenorrhea
  • Absent or sparse pubic and axillary hair
  • Testes present (often inguinal)
  • Elevated testosterone levels

38. Canavan Disease

• Genetic defect: Mutations in ASPA gene
• Diagnostic findings:
  • Macrocephaly
  • Developmental regression
  • Hypotonia
  • Seizures
  • Elevated N-acetylaspartic acid in urine

39. Familial Adenomatous Polyposis

• Genetic defect: Mutations in APC gene
• Diagnostic findings:
  • Multiple colorectal polyps
  • Increased risk of colorectal cancer
  • Congenital hypertrophy of retinal pigment epithelium
  • Desmoid tumors
  • Osteomas

40. Hereditary Hemorrhagic Telangiectasia

• Genetic defect: Mutations in ENG, ACVRL1, or SMAD4 genes
• Diagnostic findings:
  • Recurrent epistaxis
  • Mucocutaneous telangiectasias
  • Arteriovenous malformations
  • Gastrointestinal bleeding
  • Family history of similar symptoms

41. Long QT Syndrome

• Genetic defect: Mutations in various genes (e.g., KCNQ1, KCNH2)
• Diagnostic findings:
  • Prolonged QT interval on ECG
  • Syncope
  • Ventricular arrhythmias
  • Family history of sudden cardiac death
  • Torsades de pointes

42. Niemann-Pick Disease Type C

• Genetic defect: Mutations in NPC1 or NPC2 genes
• Diagnostic findings:
  • Progressive neurological deterioration
  • Hepatosplenomegaly
  • Vertical supranuclear gaze palsy
  • Ataxia
  • Dysarthria

43. Pendred Syndrome

• Genetic defect: Mutations in SLC26A4 gene
• Diagnostic findings:
  • Sensorineural hearing loss
  • Goiter
  • Enlarged vestibular aqueduct
  • Cochlear malformations
  • Euthyroid or subclinical hypothyroidism

44. Von Hippel-Lindau Syndrome

• Genetic defect: Mutations in VHL gene
• Diagnostic findings:
  • Retinal angiomas
  • Cerebellar hemangioblastomas
  • Renal cell carcinoma
  • Pheochromocytoma
  • Pancreatic neuroendocrine tumors

45. Williams Syndrome

• Genetic defect: Deletion of 7q11.23
• Diagnostic findings:
  • Elfin facies
  • Supravalvular aortic stenosis
  • Intellectual disability
  • Hypercalcemia
  • Gregarious personality

46. Xeroderma Pigmentosum

• Genetic defect: Mutations in various XP genes
• Diagnostic findings:
  • Extreme sensitivity to UV light
  • Early onset of skin cancers
  • Ocular abnormalities
  • Neurological degeneration
  • Freckling on sun-exposed areas

47. Zellweger Syndrome

• Genetic defect: Mutations in PEX genes
• Diagnostic findings:
  • Distinctive facial features
  • Hepatomegaly
  • Hypotonia
  • Seizures
  • Developmental delay

48. Lesch-Nyhan Syndrome

• Genetic defect: Mutations in HPRT1 gene
• Diagnostic findings:
  • Self-mutilating behavior
  • Intellectual disability
  • Dystonia
  • Hyperuricemia
  • Gout

49. Wiskott-Aldrich Syndrome

• Genetic defect: Mutations in WAS gene
• Diagnostic findings:
  • Eczema
  • Thrombocytopenia
  • Recurrent infections
  • Increased risk of autoimmune disorders
  • Increased risk of lymphoma

50. Werner Syndrome

• Genetic defect: Mutations in WRN gene
• Diagnostic findings:
  • Premature aging
  • Short stature
  • Early graying and loss of hair
  • Cataracts
  • Increased risk of cancer