Syndromes You Should Know

Syndrome associated with Esophageal Ca

Plummer-Vinson Syndrome

  • Patterson Kelly Syndrome = Sideropenia(iron defeciency) syn.
  • Incraese chance of Ca in:
    • Esophagus
    • Oral Cavity
    • Hypopharynx

Syndromes associated with Colorectal Ca

Familial Adenomatose Polyposis (FAP)

  • = Gardner Syndrome
  • Individuals with FAPdevelop hundred to thousands of benign colonic polyps during their early adulthood
  • If not removed by surgery —> develop into adenocarcinomas
  • Autosomal Dominant
    • 100% Pentrance
  • Gene on chromosome 5
    • Adenomatous Polyposis Coli (APC)
    • Tumor suppressor gene
    • APC also plays a role in sporadic CRC
    • In FAP —> Germline gene is mutated
    • In sporadic —> somatic cell gene is mutated
  • Also get desmoid tumours

Hereditary non-polyposis colorectal cancer (HNPCC)

  • Lynch Syndrome
  • Predisposition to Colorectal Ca
    • Also
      • Endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin.
  • Autosomal Dominant
  • Earlier than sporadic, later than FAP
  • Less severe than in FAP
    • Few tumors later in life
  • Genetic instability
    • Expansion or contraction of the length of microsatellites
    • Microsatellite instable (MSI+)
  • Genes involved:
    • MSH2 (Mut S Hololog 2)
      • Encodes a protein that is required for recognition and repair of DNA mismatches
    • MLH1
    • MSH6 (Mut S Homolog 6)
    • PMS2 (Postmeiotic segregation 2)
    • Mut L homolog 3 (MLH3)
  • ~3% of population

Cowden Syndrome

  • Lifetime risk for developing CRC: 10%
  • Risk of breast cancer: 50%
  • Other lesions:
    • Lipomas
    • Fibromas
    • Ganglioneuromas
    • Hamartomas
    • specific cutaneous lesions (facial trichilemmomas and acral verrucous papules)
    • Benign breast fibroadenomas, neurofibromas, lipomas
    • Uterine leiomyomas
    • Meningiomas
  • Germline mutations in PTEN
    • Tumor suppressor gene
      • Encoding the phosphatase and tensin homolog
      • On chromosome 10

Turcot Syndrome

Syndromes associated with Pituitary adenoma

MEN-1 Syndrome

  • Autosomal dominant
  • Tumors of
    • Pituitary
      • in 25% of patients with MEN-1 syn.
    • Parathyroid glands
    • Pancreatic islet cells. Pituitary adenomas develop in 25% of patients with MEN type-1.

Carney complex

  • rare
  • spotty skin pigmentation
  • myxomas
  • endocrine overactivity
  • schwannomas
  • Pituitary adenoma

Syndromes associated with Thyroid Papillary Ca

  • Turcot Syndrom
  • Gardner Syndrome
  • Familial Polliposis
  • Familial Papillary Syn.

Syndromes associated with soft tissue sarcoma

Li Fraumeni Syndrome

  • Rare
  • Autosomal Dominant
  • Linked with germline mutations
    • germline p53 tumor suppressor gene mutation
      • Detects damaged DNA and helps for repair or arranged cell death ( apoptosis )
  • CHEK2 mutations
    • Controls p53
  • Is activated by ATM
  • High susceptibily to CANCER
    • Breast Ca
    • Gastric Ca
    • Brain tumors
    • Acute leukemia
    • Soft tissue sarcomas
    • Bone sarcomas
    • Adrenal cortical carcinoma
  • Presents at young age
  • Multiple times of ca diagnosis

Neurofibromatosis

  • Autosomal Dominant
  • Nerve tissue grows tumor
  • Neural crest cells
  • Schwann cells
  • Melanocytes
  • Endoneural fibroblast

Syndromes associated with Thymoma

Good's Syndrome

  • Thymoma with immunodeficiency
  • Combined B and T cell immunodeficiency in adults
  • Increased susceptibility infections
    • Bacterial encapsulated organisms
    • Opportunistic viral
    • Opportunistic fungal
  • Most consistent immunological abnormalities
    • Hypogammaglobulinaemia
    • Reduced or absent B cells
  • Treatment:
    • Resection of the thymoma
    • Immunoglobulin replacement to maintain adequate trough IgG.

Myastenia Gravis

  • Autoimmune neuromuscular junction disorder
  • Presence of antiacetylcholine receptor antibodies
    • ==> Acetylcholine receptor deficiency at the motor end plate
  • Rapid exhaustion of voluntary muscular contractions, with a slow return to the normal state

Syndromes associated with Cutaneous malignancy

Gorlin Syndrome

  • Autosomal Dominant
  • Nevoid Basal Cell Carcinoma Syndrome
  • Defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones
  • PTCH mutation
  • Medulloblastoma

Turcot Syndrome

  • Multiple adenomatous colon polyps
  • Increased risk of Brain and Colon Ca
    • GBM
    • Medulloblastoma
  • Thyroid Ca
  • Autosomal Dominant
  • MLH1
  • PMS2

Von Hippel Lindau

  • Rare
  • Autosomal dominant
  • Mutation in the von Hippel–Lindau tumor suppressor gene on chromosome 3
  • Increase risk benign and malignant tumours
  • Cafe au lait spots
  • Most common tumours:
    • CNS
      • CNS tumor
      • Retinal hemangioblastomas
    • Kidney
      • RCC (Clear cell)
      • Pheochromocytomas
    • Pancreas
      • Pancreatic neuroendocrine tumours
      • Pancreatic cysts

Albinism

Xeroderma Pigmentosum

  • defect in base excision repair
  • Ultra sensitive to light and radiation
  • SCC and melanoma skin

Rothmund–Thomson syndrome

Fanconi anemia