Syndromes Flashcards
What are MDS syndromes?
MDS syndromes are irreversible disease of bone marrow stem cells that lead to ineffective and disorderly hematopoiesis characterized by abnormal division, maturation, and production of erythrocytes, granulocytes, monocytes and platelets
At what age are MDS syndromes typically diagnosed?
Sex predilection?
60 and 75
Males > females
Symptoms of MDS?
Fatigue
Weakness
Malaise
Infections (neutropenia)
Bleeding (thrombocytopenia)
Patients that present with splenomegaly may also have what underlying condition?
CMML
Name 4 MDS with refractory in the name?
Refractory anemia
Refractory anemia with ring sideroblasts (RARS)
Refractory cytopenia with multilineage dysplasia (RCMD)
Refractory anemia with excess blasts (RAEB)
Name 4 additional MDS syndromes begining with 5q-
5q-syndrome
Therapy-related MDS and therapy-related AML
MDS, unclassifiable
CMML
Gastrinoma (pancreas, duodenum, stomach or upper jejunum)
Massive gastric acid-hypersecretion with elevated basal serum gastrin levels (above 200 pmol/L)
Peptic ulceration; ulcers frequently multiple and occur in unusual site
Zollinger-Ellison Syndrome
HAD neurocutaneous syndrome characterized by hemangioblastomas (cerebellar and retinal), visceral cysts and tumors
von Hippel-Lindau
What is chromosomal mutation of vHL syndrome?
Mutations on chromosome 3p25-26 encodes pVHC protein that forms complex with tumor suppressor function
vHL abbreviated with 3 letters for chromosome 3
Name two papillary associations with vHL
Endolymphatic sac tumor (aggressive papillary middle-ear tumor)
Epididymis (papillary cystadenoma)
Name 4 other tumors associated with vHL?
NPRA
Neurofibroma
Pheo
RCC
Angiomyolipoma
HAD neurocutaneous syndrome characterized by cutaneous and neurological manifestations (mental retardation and seizures) and tumors?
Tuberous Sclerosis
What are mutations of TSC?
Mutations in either chromosome
9q34 (TSC1)
16p13 (TSC2)
What are cutaneous manifestations of TSC?
Angiomas
Adenoma sebaceum
A sh-leaf spots
Shagreen patches
Cafe-au-lait spots
Fibromas (trunk, gingivae, periungual region, hairline and eyebrows)
What are neurologic manifestations?
Neurologic manifestations:
Seizures
Mental retardation
Capillary-venous lesions on face (port-wine stain), a special type of nevus flammeus, always include portion innervated by ophthalmic division of trigenimal nerve and leptomeninges
What Syndrome?
Sturge-Weber
What is the spinal counterpart associated with limb enlargement called?
Klippel-Trenaunay-Weber
What is the chromosome for NF II
22q12
What is the protein of NFII
Merlin
Bilaterla 8th cranial nerve (vestibular branch of acoustic nerve) schwannomas are diagnostic of?
NF II
Other things associated with NF II
Unilateral 8th cranial nerve schwannoma and any 2 of the following:
Neurofibroma
Meningioma
Glioma
Schwannoma
Juvenile posterior subcapsular lenticular opacity/juvenile cortical cataract
NF II associated central nervous system lesions:
Multiple glial microharmartomas
Spinal cord cellular ependymal ectopias
Syringomelia
What syndrome is characterized by the following?
6 or more cafe-au-lait macules over 5 mm in greates diameter in a prepubertal patient, and over 15 mm in greatest diameter in a postpubertal individual
2 or more neurofibromas of any type or 1 plexiform neurofibroma
Presence of freckles in the axillary or inguinal region
Optic glioma (tumor of optic pathway)
2 or more Lisch nodules (benign pigmented iris hamartomas)
An osseous lesion such as a sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis
NF I
What is the chromosome of NF I
17q1.2
What is the protein lost in NF I
Neurofibromin
What are some NF I associated tumors?
NF-1 associated tumors:
Bilateral pheochromocytoma
Angiomyolipoma
RMS
Duodenal paraganglioma and carcinoid tumor
Somatostinoma
Ganglioneuroma
Juvenile chronic myelogenous leukemia
Juvenile xanthogranulomas
Non-ossifying fibroma
What Syndrome?
Germ line mutation in ret protooncogene, which is a tyrosine kinase receptor that is constitutively activated, causing a gain of function (chromosome 10q11)
C cell hyperplasia, medullary carcinoma (bilateral) 100%
Adrenal medullary hyperplasia, pheochromocytoma
Parathyroid hyperplasia, adenoma
Chief cell hyperplasia or multiglandular adenomas
Conservative surgery to remove only the enlarged glands
Cutaneous lichen amyloidosis (2nd to repeated scratching of neurological pruritis)
MEN IIA
Sipple Syndrome
Williams Syndrome
C cell hyperplasia —> medullary carcinoma
Adrenal medullary hyperplasia —> pheo
GI and ocular ganglioneuromas
Marfanoid habitus
Characteristic facies:
Soft tissue prognathism
Bumpy lips
Broad base of nose
Everted eyelids
Low set ears
Bowel dysfunction (diarrhea, constipation)
MEN IIB (III)
Encoded protein called menin that is a tumor suppressor (11q13)
Parathyroid hyperplasia (15% present with 5 glands)
Pancreatic (dysplasi and tumor)
Pituitary adenomas
Adrenocortical tumors
Thyroid (adenomas)
Bronchi (carcinoid tumors)
Thymus (males)
Stomach
Subcutaneous (lipomas)
MEN 1 (Wermer Syndrome)
Mutation of GNAS 1 gene causes?
McCune-Albright Syndrome
What chromosome is GNAS1 located?
20q13
What are clinical manifestations of McCune Albright syndromes?
Polyostotic fibrous dysplasia
Multiple endocrinopathies
Sexual precocity
Pituitary adenoma (acromegaly)
Adrenocortical adenoma (Cushing)
Hyperthyroidism
Hyperparathyroidism
Other reported abnormalities
GI polyps, hyperplasia of spleen, thymus and pancreatic islets
Hepatobiliary disease, cardiac disease, failure to thrive, metabolic acidosis, abnormalities in serum electrolites, glucose or insulin levels; hyperphosphaturic hypophosphatemia; malignant bone tumors’ benign bone tumors; developmental delay, microcephaly, sudden or premature death, mucoceles of head and neck, cutaneous pigmentation, intramuscular myxoma
Clinical manifestations of Mazabraud Syndrome
Polyostotic fibrous dysplasia
Soft tissue (usually intramuscular) myxoma
SBLA syndrome (sarcoma, breast cancer, leukemia, and adrenocortical cancer)
HAD
?
Li-Fraumeni
What is mutation and what chromosome of Li-Fraumeni Syndrome
Affected family members carry a p53 mutation located on chromosome 17p13 in all somatic cells
What are diagnostic considerations of Li-Fraumeni syndrome?
Diagnostic criteria:
Occurrence of sarcoma before age 45
At least 1 1st degree relative with any cancer before 45
A 1st (or 2nd) degree relative with cancer before age 45 or sarcoma at any age
In a child, what tumor is almost diagnostic of Li-Fraumeni Syndrome?
Adrenocortical carcinoma
What syndrome is associated with:
Skeletal anomalies, lamellar calcium deposition in the falx cerebri and diaphragma sellae
Cutaneous epidermoid cysts
Bifid ribs and vertebral anomalies
Pits on the palms and sole
Odontogenic keratocysts
Calcifying ovarian fibromas
Multifocal basal cell carcinomas occurring at an early age
Medulloblastoma (usually develops before age of 5 and occurs in 3% to 5% of patients)
Gorlin Syndrome (NBCCS)
Nevoid Basal Cell Carcinoma Syndrome
Where is the tumor suppresor gene associated with Gorlin syndrome located?
9q
A strong predisposition to medullary thyroid cancer without the other clinical manifestations of MEN IIA or MENIIB is called?
Familial Medullary-Thyroid Cancer
Medulloblastoma
Mental and growth retardation
Joint laxity
Branchydactyly of 5th digit with hypoplasia/aplasia of nail bed
Coffin-Siris Syndrome
Gastric epithelial leiomyosarcoma
Pulmonary chondroma
Functioning extra-adrenal paraganglioma
Carney Triad
What is the HAD mutation in Carney Syndrome?
PRKAR1A
type 1x regularoty subunit of a protein kinase that acts on a tumor suppressor gene on chromosome 17q22-24 in 50%
What are clinical manifestations of Carney Syndrome?
Myxomas: Cardiac, skin, breast
Lentiginosis and blue nevi
Endocrine tumors
Large-cell calcifying Sertoli cell tumor
Steroid-type tumor
Pituitary adenoma
Schwannomas especiallly psammomatous melanotic schwannomas
Hemihypertrophy
Organomegaly
Exophthalmos and macroglossia
Omphalocele
Increased risk of hepatoblastoma and rhabdomyosarcoma
Renal pathology
Predisposition to develop Wilms tumor
Renal medullary cysts
Mesoblastic nephroma
Adrenal pathology
Enlarged adrenal glands with cortical cytomegaly
Adrenal cortical carcinoma
Neuroblastoma
Pancreatic pathology
Pancreatic islet cell hyperplasia
Pancreatoblastoma
Beckwith-Wiedemann Syndrome
What chromosome is affected in Beckwith-Wiedemann Syndrome
11p15
Characterized by cerebellar ataxia (hallmark of disease)
Patients are unable to walk by the age of 10
Oculocutaneous telangiectasia
Progeric skin changes
Immune dysfunction
Increased cancer susceptibility
Ataxia Telangiectasia
ATM gene is located on what chromosome?
11q22-23
