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P
ediatric
cancer
and
L
i
-F
raumeni
/L
i
-F
raumeni
-
like
syndromes
:
a
review
for
the
pediatrician
R
ev
A
ssoc
M
ed
B
ras
2015; 61(3):282-289
287
know. Once a mutation is identified in a patient, first-de-
gree relatives will have a 50% chance of also being carri-
ers, and many will be cancer-unaffected at the time of in-
vestigation. In current practice, the burden (moral duty)
of informing other relatives of this risk, and providing
initial information on the possible need for genetic in-
vestigation, usually lies with the index case. In this sce-
nario, the repercussions of the patient’s unwillingness to
know are not restricted to immediate relatives, but may
extend to other members of the family as well.
55,56
Most
patients understand they have a duty to inform their rel-
atives themselves, but opinions are divided as to the duty
of providers to warn family members if the patient fails
to do so.
57
Other ethically complex scenarios emerge when
the index case dies before test results become available,
raising repercussions among living relatives,
58
or when
patients who are aware of their testing results decide not
to share them with the family, or die before they can do
so. Ideally, an agreement should be reached before the
test as to who may be informed of its results if one of the
above situations arises.
Another point of ethical concern, which is particular-
ly common in Brazil, is the performance of genetic testing
within a research setting, but for purposes of patient care.
Since the publicly-funded Unified Health System does not
cover genetic testing for LFS/LFL and other cancer predis-
position syndromes, genetic testing under the
aegis
of a re-
search project is an alternative avenue for access to this in-
formation. In this setting, research support is “necessary”
to enhance diagnosis. The providers involved in care of
these patients must assess the extent to which patients are
in a vulnerable situation and which clinical benefits they
can derive from research involvement. The relationships
between patient care and clinical research, between provid-
ers and their patients, between patients and their relatives,
and between individual
versus
group benefits, as well as
concerns related to individual and relational privacy, are
increasingly the subject of ethical reflections and prompt
questions as to how far these issues are taken into account
during the provision of genetic counseling and patient care
in hereditary breast cancer scenarios.
C
onclusion
Although LFS/LFL is considered a rare disease, affecting
approximately 1 in 2.000-5.000 individuals worldwide, it
appears to be substantially more common in Southern
and Southeastern regions due to a specific
TP53
found-
er mutation (p.R337H), present in 1 in 300 newborns. A
recent study conducted in this region of Brazil suggests
that 25% of children diagnosed with tumors of the LFS/
LFL spectrum fulfill criteria for genetic testing for the
disease. Pediatricians should be aware of the possibility
of LFS/LFL in: (1) children without cancer and with a
family history fulfilling LFS/LFL criteria and (2) children
with cancer, particularly those with tumors of the LFS/
LFL spectrum. A diagnosis of LFS/LFL have major reper-
cussions for patients and their families, as the pattern of
inheritance is well established, confirmatory genetic test-
ing is available. Additionally, interventions designed to
reduce the risk of cancers can be prescribed and have
shown effectiveness in the early diagnosis of tumors, with
significant impact on survival. Ideally diagnosis and ge-
netic counseling for patients and families with suspect-
ed LFS/LFL should be undertaken by a multidisciplinary
team. Pediatricians, pediatric oncologists and other health
care providers involved with the care of children with can-
cer have a central role in the identification of individuals
at high risk for cancer predisposition syndromes.
A
uthors
’
contributions
CR, JG and PAP reviewed all the topics. CBON, PSS, SGS
and ALM reviewed the topics’ assessment of a suspected
case of LFS/LFL, differential diagnosis and genetic coun-
seling and management of families with LFS/LFL. VZO
reviewed the topic psychological aspects and JRG reviewed
the topic bioethical aspects.
R
esumo
Câncer pediátrico e síndrome de Li-Fraumeni/Li-Frau-
meni-like: uma revisão para o pediatra.
Introdução:
o câncer é a segunda principal causa de mor-
te em crianças com idades entre 0 e 14 anos, correspon-
dendo a cerca de 3% de todos os casos diagnosticados no
Brasil. Um percentual significativo (5-10%) dos cânceres
pediátricos são associados a síndromes hereditárias para
câncer, incluindo Li-Fraumeni/Li-Fraumeni-like síndro-
mes (LFS/LFL), causadas por mutações germinativas no
gene
TP53
. Estudos recentes têm demonstrado que uma
mutação específica em
TP53
, conhecida como p.R337H,
está presente em 1 em 300 recém-nascidos no Sul e Su-
deste do Brasil. Além disso, um percentual significativo
de crianças com tumores do espectro LFS/LFL na região
têm uma história familiar compatível com a síndrome.
Objetivos:
revisão dos aspectos clínicos relevantes da
LFS/LFL por equipe multidisciplinar, com foco no cân-
cer pediátrico.
Métodos:
o NCBI (PubMed) e SciELO foram consulta-
dos, usando as palavras-chave síndrome de Li-Fraumeni,