Hemepath: Non-Neoplastic Wbc

Front 1

Constitutional WBC disorders due to proliferation defects (hypoplasia)

Back 1

Fanconi anemia
Kostmann's syndrome
Schwachman-Diamond syndrome
Cyclic neutropenia

Front 2

Fanconi anemia

Back 2

- most common of the rare hereditary bone marrow failure syndromes
- autosomal recessive
- about 13 genes
- patients are homozygous or double heterozygotes
- eg BRAC2(aka FANCD1 gene)
- variable presentation
- FA proteins play role in DNA repair mechanisms

- 1 in 300 carrier frequency (Ashkenazi jew: 1 in 90!)

- The major cause of death in FA is bone marrow failure, followed in frequency by leukemia/MDS and solid tumors
- median survival 20-30yrs

- The most common tumors are liver adenomas and hepatomas, primarily in patients who had aplastic anemia that was treated with oral androgens.

-The risk of liver tumors is increased 400-fold, the risk of leukemia and head and neck cancers is increased 700-fold, the risk of esophageal cancer is increased 2000-fold, and the risk of vulvar cancer is increased 4000-fold.

- main concerns in children/adolescents(BM failure and leukemias) vs. adults when solid tumors become more problematic

- characteristic birth defects (eg, radial ray anomalies, poor growth, genitourinary problems)
- 75% of patients with FA have birth defects, such as altered skin pigmentation and/or café au lait spots (>50%), short stature (50%), thumb or thumb and radial anomalies (40%), abnormal male gonads (30%), microcephaly (25%), eye anomalies (20%), structural renal defects (20%), low birth weight (10%), developmental delay (10%), and abnormal ears or hearing (10%).

Front 3

Kostmann's syndrome

Back 3

- rare severe congenital neutropenia of infancy (early infancy)
- auto recessive, sporadic, auto dominant cases
- mutationas in ELA2 gene (neutriphil elastase) - defect in myeloid precursors leading to promyelocyte/myelocyte arrest with few maturing forms; but neutrophil survival is normal

Front 4

cyclic neutropenia

Back 4

- present with recurrent symptomatic infections (fatigue, mouth ulcers, cervical LAD, fever)
- cyclic severe neutropenia
- presents in childhood (maybe adulthood)
- 21-day cycle of oscillating neutrophil and monocyte counts (normal to very low)
- mutations in ELA2 gene (neutrophil elastase gene) leas to selective apoptosis of neutrophil progenitors (similar mechanisms to Kostmann's syn)

Front 5

Chronic familial neutropenia (benign familial neutropenia)

Back 5

lower than normal neutrophil count
- incidental genetic variation

Front 6

two most common causes of congenital neutropenia are __

Back 6

- neutropenia of pregnancy-induced hypertension [PIH](most common)
- overwhelming bacterial infection (w/ s/sx of infection)

Neither should persist beyond first week of life

Front 7

Constitutional WBC disorders due to proliferation defects (hypoplasia)

Back 7

Fanconi anemia
Kostmann's syndrome
Schwachman-Diamond syndrome
Cyclic neutropenia

Front 8

Fanconi anemia

Back 8

- most common of the rare hereditary bone marrow failure syndromes
- autosomal recessive
- about 13 genes
- patients are homozygous or double heterozygotes
- eg BRAC2(aka FANCD1 gene)
- variable presentation
- FA proteins play role in DNA repair mechanisms

- 1 in 300 carrier frequency (Ashkenazi jew: 1 in 90!)

- The major cause of death in FA is bone marrow failure, followed in frequency by leukemia/MDS and solid tumors
- median survival 20-30yrs

- The most common tumors are liver adenomas and hepatomas, primarily in patients who had aplastic anemia that was treated with oral androgens.

-The risk of liver tumors is increased 400-fold, the risk of leukemia and head and neck cancers is increased 700-fold, the risk of esophageal cancer is increased 2000-fold, and the risk of vulvar cancer is increased 4000-fold.

- main concerns in children/adolescents(BM failure and leukemias) vs. adults when solid tumors become more problematic

- characteristic birth defects (eg, radial ray anomalies, poor growth, genitourinary problems)
- 75% of patients with FA have birth defects, such as altered skin pigmentation and/or café au lait spots (>50%), short stature (50%), thumb or thumb and radial anomalies (40%), abnormal male gonads (30%), microcephaly (25%), eye anomalies (20%), structural renal defects (20%), low birth weight (10%), developmental delay (10%), and abnormal ears or hearing (10%).

Front 9

Kostmann's syndrome

Back 9

- rare severe congenital neutropenia of infancy (early infancy)
- auto recessive, sporadic, auto dominant cases
- mutationas in ELA2 gene (neutriphil elastase) - defect in myeloid precursors leading to promyelocyte/myelocyte arrest with few maturing forms; but neutrophil survival is normal

Front 10

cyclic neutropenia

Back 10

- present with recurrent symptomatic infections (fatigue, mouth ulcers, cervical LAD, fever)
- cyclic severe neutropenia
- presents in childhood (maybe adulthood)
- 21-day cycle of oscillating neutrophil and monocyte counts (normal to very low)
- mutations in ELA2 gene (neutrophil elastase gene) leas to selective apoptosis of neutrophil progenitors (similar mechanisms to Kostmann's syn)

Front 11

Chronic familial neutropenia (benign familial neutropenia)

Back 11

lower than normal neutrophil count
- incidental genetic variation

Front 12

two most common causes of congenital neutropenia are __

Back 12

- neutropenia of pregnancy-induced hypertension [PIH](most common)
- overwhelming bacterial infection (w/ s/sx of infection)

Neither should persist beyond first week of life