Supplementary Table 1 Other hereditary cancer syndromes with some gastrointestinal involvement.61
Syndrome
Gene(s)
Inheritance Component
Features other than component
(chromosomal pattern
gastrointestinal
gastrointestinal neoplasms
locus)
neoplasms
Malignant
Benign neoplasms
neoplasms
and other features
Ataxia
telangiectasia
ATM (11q22.3)b
AR
Pancreas and
stomach cancers
Bannayan-RileyRuvalcaba
syndrome
PTEN (10q23)b
AD
Hamartomas
(juvenile,
ganglioneuromas,
lipomas,
inflammatory)
throughout
gastrointestinal
tract
BeckwithWiedemann
syndrome
BWS (11p15) b
Sporadic with
occasional
AD
Gastric teratoma;
hepatoblastoma;
hepatocellular
carcinoma
Bloom syndrome
BLM/RECQL3
(15q26.1) b
AR
Esophageal, gastric
and colon cancer
Blue rubber bleb
nevus syndrome
TIE2 (9p21)?
AD
Gastrointestinal
tract hemangiomas
Cowden
syndrome
PTEN (10q23) b
AD
Hamartomas
(juvenile,
ganglioneuromas,
lipomas,
inflammatory)
throughout
gastrointestinal
tract
Breast, uterine,
thyroid (papillary
& follicular),
ovarian, renal
and bladder
(transitional cell)
cancers;
melanoma
Familial carcinoid
syndrome
SDHD (11q23) b
Others?
AD
Intestinal and
appendiceal
carcinoid tumors;
malignant carcinoid
tumor of the ileum
None
Fanconi anemia
At least 13
different genes;
of note: FANCD1
(BRCA2b) and
FANCN (PALB2)
AR
Esophageal, anal
and hepatocellular
carcinoma
MDS; leukemia;
head/neck,
cervix, vulva and
multiple other
solid tumors
Gorlin syndromea
PTCH1 (9q22.3)b
AD
Lymphomesenteric
cysts (often
calcified); stomach
hamartomas
Basal cell
carcinomas
Non-Hodgkin’s
lymphoma;
leukemia; breast
and ovarian
cancer;
melanoma
Same as
Cowden
syndrome
Wilm’s tumor;
adrenocortical
carcinoma;
rhabdomyosarco
ma;
neuroblastoma
Non-Hodgkin’s
lymphoma; acute
leukemia; oral,
laryngeal, lung,
skin, breast and
cervical cancers
None
Cerebellar ataxia;
choreoathetosis;
dysarthria; endocrine
dysfunction;
immunodeficiency;
telangiectasias
Cowden syndrome
features plus proximal
myopathy; joint
hyperextensibility;
pectus excavatum;
scoliosis; pigmented
macules on penis;
mental retardation
and/or developmental
delay
Exomphalos;
macroglossia;
gigantism; mental
retardation
Severe growth
deficiency; “butterfly
rash”; malar hypoplasia;
nasal prominence; small
mandible;
dolichoencephaly
Blue or green bladderlike skin hemangiomas;
hemangiomas of eyes,
pharynx and uterus
Macrocephaly;
mucocutaneous lesions
(papillomatous papules,
acral/plantar keratoses,
trichilemommas);
Lhermitte-Duclos
disease; fibroids; benign
breast and thyroid
disease; meningioma
None
Duodenal atresia;
intestinal malrotation;
skeletal anomalies; skin
hyperpigmentation;
renal anomalies;
microcephaly; mental
retardation
Jaw cysts; palmar and
plantar pits; cardiac and
ovarian fibromas;
meningiomas; tall
stature; macrocephaly;
frontal bossing;
hypertelorism; skeletal
Hereditary breast
and ovarian
cancer syndrome
BRCA1 (17q21) b
BRCA2 (13q12) b
AD
Hyperparathyroidi
sm-jaw tumor
syndrome
HRPT2 (1q25) b
AD
Li-Fraumeni
syndrome
TP53 (17p13.1) b
Multiple
endocrine
neoplasia type 2b
Pancreas, bile duct
and gallbladder
cancers; colon
and/or gastric
cancers?67
Pancreatic cancer
Female and male
breast, ovarian
and prostate
cancer;
melanoma
Parathyroid and
renal (papillary)
carcinoma;
Wilms tumor
AD
Colorectal,
stomach and
pancreatic cancer
RET (10q11.2) b
AD
Ganglioneuromatos
is of the intestine
Sarcoma; breast,
adrenocortical
and brain
camcers;
leukemia;
lymphoma; many
other cancers
Medullary thyroid
cancer;
pheochromocyto
ma
NAME syndrome
CNC2 (2p16)
PRKAR1A
(17q23)b
Others?
AD
Colorectal and
pancreatic cancer
Large cell
calcifying SertoliLeydig tumors;
liposarcomas;
testes and
thyroid cancer
Tuberous
sclerosis
TSC1 (9q34)b
TSC2 (16p13.3)b
AD
Hamartomatous
rectal polyps
Astrocytomas;
Wilm’s tumor;
renal cell
carcinoma
von HippelLindau syndrome
VHL (3p25)b
AD
Pancreatic cysts
and cystadenomas;
islet cell tumors
and PNET
Xeroderma
pigmentosum
7 different genes
AR
Stomach cancer
Retinal and CNS
hemagioblastom
as;
pheochromocyto
mas;
paragangliomas
Basal and
squamous cell
carcinomas;
cutaneous
angiosarcomas;
leukemia; solid
tumors
aAlso
malformations;
developmental delay
None
Hyperparathyroidism;
solitary parathyroid
adenoma; renal cortical
adenoma; Hurthle cell
thyroid adenoma; renal
cysts; renal
hamartomas; multiple
ossifying fibromas of the
mandible and maxilla
None
Marfanoid habitus;
mucosal neuromas;
“blubbery” lips;
hyperparathyroidism/par
athyroid adenomas
Carney Complex
(cardiac myxoma,
spotty pigmentation and
cutaneous myoxmas,
and pituitary and
adrenocortical
carcinomas) and LAMB
in addition to features
described in the
acronym
Facial angiofibromas;
ungual fibromas;
shagreen patch; cortical
tubers; subependymal
nodule or giant cell
tumors; retinal
hamartomas; cardiac
rhabdomyomas; renal
angiomyolipoma;
lymphangiomyomatosis;
cognitive disability
endolymphatic sac
tumors; renal cysts
Severe freckling or
blistering; irregular
pigmentation; abnormal
sensitivity to UV light;
poikilodermas;
epitheliomas; angiomas;
fibromas;
keratoacanthomas and
keratoses
known as nevoid basal cell carcinoma syndrome. bGenes for which there is a commercially available
genetic test.27 Abbreviations: AD, autosomal dominant; AR, autosomal recessive; LAMB, lentigines, atrial
myxomas, mucocutaneous myxomas and blue nevi; MDS, myelodysplastic syndrome; NAME, nevi, atrial
myxoma, myxoid neurofibromas, and ephelides; PNET, primitive neuroectodermal tumor.