Category Archives: Syndrome

Neurofibromatosis type 1

Neurofibromatosis type 1

•    gene NF1, on chromosome 17
•    neurofibromas throughout body = plexiform neurofibroma or solitary neurofibroma
•    cafe au lait spots = hyperpigmented spots (increased melanin in basal layer)
•    Lisch nodules = pigmented nodules on the iris
•    many other tumors: neuroblastoma, ganglioneuroma, Wilms, lipoma, GIST, pheochromocytoma

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Neurofibromatosis type 2

Neurofibromatosis type 2

•    gene NF2, on chromosome 22q12
•    bilateral acoustic (actually vestibular) CNVIII schwannomas
•    multiple meningiomas
•    gliomas, usually ependymomas

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Tuberous Sclerosis

Tuberous Sclerosis

- autosomal dominant transmission or sporadic

Genetics

TSC1: hamartin, TSC2: tuberin

Pathology

Brain and Retina → hamartomas (glial)
Lungs and Heart → myomas
Kidneys → angiomyolipomas, cysts
Liver and Pancreas → cysts
Skin → angiofibromas

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von Hippel Lindau

von Hippel Lindau Syndrome

•    multifocal and bilateral
•    VHL (von Hippel Lindau) tumor suppressor gene is hypermethylated or mutated
•    maps to 3p25

Features of von Hippel Lindau syndrome

→ pheochromocytomas
→ Hippel
→ multicystic kidneys
→ retinal hemangiomas, cerebellar hemangioblastomas

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Sturge Weber Syndrome

Sturge Weber Syndrome

- skin and brain angiomas
- in trigeminal nerve distribution

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Juvenile Polyposis Syndrome

Juvenile Polyposis Syndrome

Inheritance: sporadic or autosomal dominant
often mutations in PTEN or smad4/dpc4

Diagnosis criteria:
a) >5 colorectal juvenile polyps
b) juvenile polyps in entire GI tract
c) any polyps in a patient with a family history of Juvenile Polyposis Syndrome

Gross: peduculated polyp

Histology

- eroded surface with reactive and regenerative epithelium
- cystically-dilated glands
- prominent stroma with a mixed inflammatory infiltrate

Genetics: SMAD4, BMDR1A mutation

Associations: adenomas, cancers of the stomach to colon and pancreas

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Peutz-Jeghers Syndrome

Peutz-Jeghers Syndrome

Inheritance: Autosomal dominant with incomplete penetrance
Genetics: STK11 germline mutations

Diagnosis criteria:
a) 3+ Peutz-Jeghers polyps
b) Peutz-Jeghers with family history
c) mucocutaneous pigmentation and Peutz-Jeghers polyp or family history

Gross: large, lobulated, pedunculated polyps resembling adenomatous polyps

Histology:
- hyperplasia of epithelium with arborizing branches of smooth muscle
- surface regenerative changes with erosion

Genetics: 95% overall cancer risk

- screening and surveillance of gastrointestinal and gynecologic organs:
Gastrointestinal
Gynecologic, Breast: Ovary, Uterus, Cervix, Breast

PEUTZ-JEGHERS SYNDROME
Inheritance: AD w/ incomplete penetrance
Genetics: STK11 germline mutations
Dx criteria:
a) 3+ PJ polyps
b) PJ w/ family hx
c) mucocutaneous pigmentation + PJ polyp or family hx.
Gross: large, lobulated, pedunculated polyps resembling adenomatous polyps
Micro:
-HP of epithelium with arborizing branches of smooth muscle
-surface regenerative changes with erosion
Genetics: 95% overall ca. risk! ®so, screening and surveillance of GI and gyne organs:
GI
Gyne/Breast: Ovary, Uterus, Cervix, Breast
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Cowden’s Syndrome

Cowden’s Syndrome

Inheritance: Autosomal dominant

Features
- multiple hamartomas
-­ risk of breast and thyroid cancer

Histology:

- hamartomatous polyps with disorganization, proliferation and splaying of muscularis mucosa

Genetics: germline PTEN mutations in 70%

Differential diagnosis:

- Peutz-Jeghers

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Sjogren’s Syndrome

Sjogren’s Syndrome

What is Sjogren’s Syndrome?

Sjogren’s Syndrome is a chronic autoimmune disease which affects the lacrimal and salivary exocrine ducts. Also affects the GI tract and respiratory tract and vagina and kidney

Clinical features of Sjogren’s Syndrome:

•    keratoconjunctivitis
•    xerostomia
•    nasal septum perforation
•    pulmonary fibrosis

Sjogren’s Syndrome pathology:

Minor and major salivary glands:

1. periductal and perivascular lymphocytic infiltrates.
2. lymphoid hyperplasia with follicle centres
3. fibrosis, atrophy of ducts
4. fat replacement of parenchyma

Sjogren’s Syndrome Kidney Disease:

- tubular interstitial nephritis

Sjogren’s Syndrome Antibodies:

•    ANA, RF
•    ANS → specific Ab are SS-A and SS-B

How to diagnosis Sjogren’s Syndrome:

- biopsy of the lower lip to check minor salivary glands

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Fragile X Syndrome

Fragile X Syndrome

- second most common cause of MR

- X-linked disorder

What is the nucleotide repeat sequence?

-trinucleotide expansion of FMR gene of “CGG”

What are the clinical features?

- long face, big ears,

What is Sherman’s paradox?

- risk of MR higher in grandson than the brother of the transmitting male. Because the premutation is amplified to a mutation during oogenesis → resulting in all males with MR and 50% of females.

What is anticipation?

-mutation gets worse with each generation.

What is the difference between premutations and mutations?

- premutations: normal transmitting males and carrier females

- mutations (>230 repeats) → results inactivation of FMR1

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