Pediatric Oncology

Question 1

What percent of childhood cancers are hereditary?

Answer 1

10%

Question 2

What are six childhood cancers that warrant an evaluation by genetics?

Answer 2

Osteosarcoma
Ewing sarcoma
CNS tumors
Neuroblastoma
Wilms tumor
Rhabdomyosarcoma

Question 3

When is an oncology referral to genetics indicated

Answer 3

• Tumor type
• Somatic findings suggestive of a germline predisposition
• Laterality (bilateral, multifocal, multiple primary tumors)
• Family Hx
• ≥2 malignancies in family members dx <18yo (proband included)
• FDR w/ hx of cancer dx <45yo
• ≥2 FDR or SDR w/ hx of cancer dx <45yo
• Consanguinity
• Other clinical findings
• Congenital or other anomalies
• Toxicity related to therapy

Question 4

What is Constitutional Mismatch Repair Deficiency?

Answer 4

Autosomal recessive disorder caused by mutations in the Lynch Syndrome genes (MSH2, MSH6, PMS2, MLH1) that causes predisposition to cancer

Question 5

What are some of the findings in CMMRD?

Answer 5

CALM
Skin hypopigmentation
Lisch nodules

Question 6

What are the most prevalent cancers in CMMRD?

Answer 6

Brain tumors
Hematological malignancies
LS associated cancers

Question 7

What is the average age of onset for CMMRD?

Answer 7

12-30 years

Question 8

What screening is recommended in CMMRD?

Answer 8

MRI brain, whole body MRI, CBC, Abdominal US, Upper GI endoscopy, ileocolonoscopy, gyn exam, transvaginal US, urine test

Question 9

What is DICER1 syndrome?

Answer 9

DICER1 syndrome is an inherited disorder that increases the risk of a variety of cancerous and noncancerous (benign) tumors

Tumors that occur in the lungs, kidneys, ovaries, and thyroid

Question 10

What is the lung tumor that occurs in DICER1 syndrome and what is the screening recommendation for the lungs?

Answer 10

Pleuropulmonary blastoma (PPB)

Chest x-ray at birth, every 4-6 mos until age 8 yrs, then annually until age 12

Consider chest CT at age 3-6 mos. If initial CT normal: consider repeat CT at age 2.5-3 yrs.

Question 11

What is the genetic cause of Rhabdoid Tumor Predisposition syndromes?

Answer 11

SMARCB1 (>98%), SMARCA4 (<2%)

Question 12

What are the tumor types found in rhabdoid tumor predisposition syndrome (RTPS type I)?

Answer 12

Rhabdoid tumor (>90% will develop by 5yo)
Schwannomatosis (SMARCB1 may be candidate gene)
Multiple meningiomas
Malignant peripheral nerve sheath tumor

Question 13

What are the tumor types found in rhabdoid tumor predisposition syndrome (RTPS type II)? (SMARCA4)

Answer 13

Small cell carcinoma of the ovary (40% of females will be +SMARCA4)
Malignant rhabdoid tumor and atypical teratoid

Question 14

What is the screening in Rhabdoid Tumor Predisposition Syndrome (RTPS)?

Answer 14

Neurological exam
US of abdomen, neck and head
Brain and spine MRI or WBMRI

Question 15

What are the findings in Ataxia-Telangiectasia (AT)?

Answer 15

Telangiectasia
Ocular telangiectasia by 6 years
Neurodegeneration (progressive gain&truncal cerebella ataxia–1-4yrs)
By 10 years in wheelchair
Immune defects
Radiosensitivity
Sterility (ovarian failure)
Cancer

Question 16

What is the gene that causes Ataxia-Telangiectasia and what is the mode of inheritance?

Answer 16

ATM

Autosomal Recessive

Question 17

What are the cancer risks in Ataxia-Telangiectasia?

Answer 17

T-ALL, NHL, HL, AML

Question 18

What are the cancer risks in Fanconi Anemia?

Answer 18

Acute myeloid leukemia (AML)
SCC
-Head & Neck (most common solid tumor and more often occur on the tongue)
-Esophagus, vulva
-Cervical cancer
-Liver tumors

Question 19

What is the phenotype of Fanconi Anemia (BRCA2)?

Answer 19

Early-onset acute leukemia and solid tumors
-97% chance of malignancy to develop by 6yo

Add abdominal ultrasound and brain MRI in screening

Question 20

What is the phenotype of Fanconi Anemia (FANCB)?

Answer 20

early-onset bone marrow failure & severe congenital abnormalities

Question 21

What is the phenotype of Fanconi Anemia (FANCG)?

Answer 21

severe bone marrow failure and higher incidence of leukemia

Question 22

What is the phenotype of Fanconi Anemia (PALB)?

Answer 22

solid tumors

Question 23

What are some of the surveillance recommendations for Fanconi Anemia for cancer?

Answer 23

Blood counts
bone marrow aspirate/biopsy
FISH & cytogenic testing
Liver function tests
Liver US
PAP smear starting 13 years
Exam by dentist
Nasolaryngoscopy
Dermatologist

Question 24

What is the classic triad in DYSKERATOSIS CONGENITA (DC) TELOMERE BIOLOGY DISORDERS (TBD)?

Answer 24

oral leukoplakia, reticular skin pigmentation, nail
dystrophy

Question 25

What are additional findings in DYSKERATOSIS CONGENITA (DC) TELOMERE BIOLOGY DISORDERS (TBD)?

Answer 25

-Myelodysplastic syndrome (MDS), AML, Bone Marrow Failure (BMF)
-Pulmonary Fibrosis, Emphysema
-Liver Fibrosis/Cirrhosis
-Solid tumors of the head and neck

Question 26

When should you suspect DC/TBD?

Answer 26

Two features of the classic triad

PHx and FHx of any:
-BMF
-MDS
-AML
-early-onset head/neck SCC,
-Pulmonary fibrosis

Question 27

What test besides gene panel should you order for DYSKERATOSIS CONGENITA (DC) TELOMERE BIOLOGY DISORDERS (TBD)?

Answer 27

Telomere length testing

Question 28

What is the genetic cause and mode of inheritance in NIJMEGEN BREAKAGE SYNDROME (NBJ)?

Answer 28

NBN gene
Autosomal Recessive

Question 29

What are the features of Nijmegen Breakage Syndrome?

Answer 29

-Microcephaly: >99%
-Growth Deficiency: varies w/ age, but can present at birth
-Immunodeficiency: ≥99%
-Malignancy: >60% by age 25
-Lymphomas
-CNS: Medulloblastomas, gliomas, rhabdomyosarcomas
-Ovarian germ cell tumors
-Infertility: 100% of females (premature ovarian failure)

Question 30

What percentage of DICER1 mutations are de novo?

Answer 30

20%