2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

CANCER PREDISPOSITION IN CHILDHOOD
Table 2. Hereditary Cancer Syndromes with Solid-Tumor Risk and Manifestations in Childhood: Genetics, Risks, Features, and Surveillance (Cont’d)
Syndrome Gene(s) Inheritance Cancer/Tumor Risks Other Features Cancer Surveillance
PTEN Hamartoma Tumor
syndrome 56
PTEN AD Breast
Thyroid
Endometrial
Renal
Associated benign tumors:
- Multinodular goiter
- Cystic nephroma
PTEN-associated benign tumors:
- Lipomas
- Thyroid nodules/goiter
- Hamartomatous GI polyps
Rhabdoid syndrome SMARCB1/INI1 AD Rhabdoid tumors
Schwannomatosis
von-Hippel Lindau
syndrome 57
VHL AD Hemangioblastoma (retinal/
cerebellar)
Renal Cell Carcinoma
Pancreatic–neuroendocrine
Pheochromocytoma
Endolymphatic sac tumors
Epididymal tumors
an increased risk for hyperparathyroidism and pheochromocytoma.
Although all individuals with a RET mutation have
an increased risk for MTC, there are direct genotypephenotype
correlations that predict the age of onset and
determine timing for prophylactic thyroidectomy. 37 Studies
have found that genetic identification of children at risk for
MEN2 and prophylactic thyroidectomy has greatly reduced
the likelihood of developing MTC in this population. 38
Similarly, the identification of the APC gene as the cause
of FAP has allowed for genetic testing to identify children
with this condition. Individuals with APC mutations associated
with a classic FAP phenotype develop hundreds to
thousands of colonic polyps beginning in adolescence and
have a risk of colon cancer that approaches 100% if untreated.
Current guidelines recommend beginning surveillance
for colon polyps at age 10. When polyps become too
numerous to follow endoscopically, colectomy is recommended.
39 Use of genetic testing to evaluate at-risk children
for a familial APC mutation is more cost-effective than
relying on colon examinations to determine whether a child
has inherited this condition. 40 Because of the morbidities
associated with colectomy, alternatives to surgery are being
Macrocephaly
Arteriovascular malformations
Developmental delay/
intellectual disability/
autism
Wilms tumor syndromes 58 WT1 AD Wilms tumor Aniridia (WAGR syndrome)
WAGR
Denys-Drash
Familial Wilms
Frasier
- Physical exam every 12 mo starting at age 18 y,
lifelong
- Thyroid ultrasound every 12 mo starting at age
18 y, lifelong
- Self breast exam every 1 mo starting at age 18 y,
lifelong
- Clinical breast exam every 6–12 mo starting at
age 25 y, lifelong
- Mammogram and breast MRI every 12 mo starting
at age 30–35 y (or 5–10 y before earliest age of
diagnosis in family, whichever comes first)
- Patient education about signs and symptoms of
endometrial cancer and encourage prompt followup
if issues arise
- Counsel about risk-reducing mastectomy and
hysterectomy on a case-by-case basis
- Colonoscopy (suggested) every 5–10 y, more
frequently if symptoms or polyps, starting at age
35 y, lifelong
None No published guidelines available
Renal and Pancreatic cysts - Ophthalmologic screening every 12 mo starting at
age 1 y, lifelong
- Physical exam, blood pressure monitoring, and
neurologic assessment every12 mo starting at age
2 y, lifelong
- Urine/plasma catecholamine metabolites every
12 mo starting at age 2 y, lifelong
- Abdominal ultrasound every 12 mo from age
8–20 y
- Abdominal CT or MRI every 24 mo, to be
alternated with annual abdominal ultrasound
starting at age 20 y
- Brain/spine MRI every 12 mo starting at puberty
- Audiology assessment every 2–3 y from ages
2–10 y, and then as symptoms arise
Genitourinary defects
Developmental delay/
intellectual disability/
autism
- Renal ultrasound every 3 mo from birth until age
8y
Abbreviations: AD, autosomal dominant; AML, Acute myeloid leukemia; AR, autosomal recessive; AFP, alpha-fetoprotein; BAER, brainstem auditory evoked response;
CA 19-9, carbohydrate antigen 19-9; CBC, complete blood count; CHRPE, congenital hypertrophy of the retinal pigmented epithelium; CNS, central nervous system;
CT, computed tomography; EGD, esophagogastroduodenoscopy; GI, gastrointestinal; JMML, juvenile myelomonocytic leukemia; MEN2, multiple endocrine neoplasia
type 2; mo, month (s); MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; PPB, pleuropulmonary blastoma; PTH, parathyroid
hormone; SCTAT, sex cord tumors with annular tubules; SRS, somatostatin receptor scintigraphy; WAGR, Wilms tumor, aniridia, genitourinary anomalies, and mental
retardation syndrome; wk, week(s); XRT, radiation; y, year(s).
sought. Nonsteroidal anti-inflammatory inhibitors, such as
sulindac, and Cox-2 inhibitors have been found to reduce
polyp development in adults with FAP. 41,42 Studies have
now begun to look at the potential utility of these medications
in children 43 and an international clinical trial is
currently enrolling children with a molecular diagnosis of
FAP in a 5-year trial comparing the rate of polyp development
with celecoxib compared with placebo. 44
Genetic Risk Assessment and Counseling
Elements of an appropriate cancer genetic evaluation
include collection of a thorough personal and family medical
history, genetic risk assessment through pedigree analysis
and published literature, genetic testing when appropriate
for specific cancer syndromes, informed consent, results
disclosure, and psychosocial assessment. 45 This process is
often complex and may also require other essential components
including medical records ascertainment and review,
health insurance preauthorization for testing, and facilitating
communication with other at-risk family members about
complex results.
Benefits of cancer genetic risk assessment, counseling,
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