Pediatric Oncology Flashcards
What percent of childhood cancers are hereditary?
10%
What are six childhood cancers that warrant an evaluation by genetics?
Osteosarcoma
Ewing sarcoma
CNS tumors
Neuroblastoma
Wilms tumor
Rhabdomyosarcoma
When is an oncology referral to genetics indicated
- 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
What is Constitutional Mismatch Repair Deficiency?
Autosomal recessive disorder caused by mutations in the Lynch Syndrome genes (MSH2, MSH6, PMS2, MLH1) that causes predisposition to cancer
What are some of the findings in CMMRD?
CALM
Skin hypopigmentation
Lisch nodules
What are the most prevalent cancers in CMMRD?
Brain tumors
Hematological malignancies
LS associated cancers
What is the average age of onset for CMMRD?
12-30 years
What screening is recommended in CMMRD?
MRI brain, whole body MRI, CBC, Abdominal US, Upper GI endoscopy, ileocolonoscopy, gyn exam, transvaginal US, urine test
What is DICER1 syndrome?
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
What is the lung tumor that occurs in DICER1 syndrome and what is the screening recommendation for the lungs?
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.
What is the genetic cause of Rhabdoid Tumor Predisposition syndromes?
SMARCB1 (>98%), SMARCA4 (<2%)
What are the tumor types found in rhabdoid tumor predisposition syndrome (RTPS type I)?
Rhabdoid tumor (>90% will develop by 5yo)
Schwannomatosis (SMARCB1 may be candidate gene)
Multiple meningiomas
Malignant peripheral nerve sheath tumor
What are the tumor types found in rhabdoid tumor predisposition syndrome (RTPS type II)? (SMARCA4)
Small cell carcinoma of the ovary (40% of females will be +SMARCA4)
Malignant rhabdoid tumor and atypical teratoid
What is the screening in Rhabdoid Tumor Predisposition Syndrome (RTPS)?
Neurological exam
US of abdomen, neck and head
Brain and spine MRI or WBMRI
What are the findings in Ataxia-Telangiectasia (AT)?
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
What is the gene that causes Ataxia-Telangiectasia and what is the mode of inheritance?
ATM
Autosomal Recessive
What are the cancer risks in Ataxia-Telangiectasia?
T-ALL, NHL, HL, AML
What are the cancer risks in Fanconi Anemia?
Acute myeloid leukemia (AML)
SCC
-Head & Neck (most common solid tumor and more often occur on the tongue)
-Esophagus, vulva
-Cervical cancer
-Liver tumors
What is the phenotype of Fanconi Anemia (BRCA2)?
Early-onset acute leukemia and solid tumors
-97% chance of malignancy to develop by 6yo
Add abdominal ultrasound and brain MRI in screening
What is the phenotype of Fanconi Anemia (FANCB)?
early-onset bone marrow failure & severe congenital abnormalities
What is the phenotype of Fanconi Anemia (FANCG)?
severe bone marrow failure and higher incidence of leukemia
What is the phenotype of Fanconi Anemia (PALB)?
solid tumors
What are some of the surveillance recommendations for Fanconi Anemia for cancer?
Blood counts
bone marrow aspirate/biopsy
FISH & cytogenic testing
Liver function tests
Liver US
PAP smear starting 13 years
Exam by dentist
Nasolaryngoscopy
Dermatologist
What is the classic triad in DYSKERATOSIS CONGENITA (DC) TELOMERE BIOLOGY DISORDERS (TBD)?
oral leukoplakia, reticular skin pigmentation, nail
dystrophy
What are additional findings in DYSKERATOSIS CONGENITA (DC) TELOMERE BIOLOGY DISORDERS (TBD)?
-Myelodysplastic syndrome (MDS), AML, Bone Marrow Failure (BMF)
-Pulmonary Fibrosis, Emphysema
-Liver Fibrosis/Cirrhosis
-Solid tumors of the head and neck
When should you suspect DC/TBD?
Two features of the classic triad
PHx and FHx of any:
-BMF
-MDS
-AML
-early-onset head/neck SCC,
-Pulmonary fibrosis
What test besides gene panel should you order for DYSKERATOSIS CONGENITA (DC) TELOMERE BIOLOGY DISORDERS (TBD)?
Telomere length testing
What is the genetic cause and mode of inheritance in NIJMEGEN BREAKAGE SYNDROME (NBJ)?
NBN gene
Autosomal Recessive
What are the features of Nijmegen Breakage Syndrome?
-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)
What percentage of DICER1 mutations are de novo?
20%
