Table 2. [Less Common Genes and Syndromes Associated with Wilms Tumor Predisposition]. - GeneReviews®

Gene	Syndrome	MOI	Estimated Wilms Tumor Risk ¹	Other Clinical Features
AMER1 (WTX)	Osteopathia striata with cranial sclerosis	XL	~5%	Sclerosis of cranium & long bones, macrocephaly, characteristic facial features, ±DD/ID
ASXL1	Bohring-Opitz syndrome	AD	~7%	Growth deficiency, characteristic facial features, distinct posture, seizures. cardiac anomalies, DD/ID
BLM	Bloom syndrome	AR	∼6%	Growth deficiency, immune deficiency, sun sensitivity, diabetes, multiple cancers
BRCA2	BRCA2-related Fanconi anemia	AR	∼20%-60%	Growth deficiency, congenital anomalies, dysmorphic features, early-onset leukemia, medulloblastoma. pigmentary abnormalities
BUB1B	Mosaic variegated aneuploidy syndrome (OMIM 257300)	AR	>85%	Growth deficiency, microcephaly, CNS anomalies, dysmorphic features, genitourinary anomalies, DD/ID, nephroblastoma, rhabdomyosarcoma, leukemia.
CDC73	CDC73-related disorders	AD	∼3%	Hyperparathyroidism, parathyroid adenoma & cancer, osseous fibroma(s) of the jaw
CHEK2	CHEK2 cancer susceptibility (OMIM 609265)	AD	∼3%	Breast cancer, ↑ risk of some additional cancers (prostate, GI, sarcomas, renal)
CTR9	Familial WT ²	AD	>60%	Paternally inherited
DICER1	DICER1 tumor predisposition	AD	<1% ³	Pleuropulmonary blastoma, pulmonary cysts, thyroid gland neoplasia, ovarian tumors, & cystic nephroma, ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma, pineoblastoma, pituitary blastoma
GLOW syndrome (See DICER1 Tumor Predisposition.)	Somatic mosaic / AD ⁴	Unknown; possibly >50%	GLOW; also macrocephaly, characteristic facial features, autism
DIS3L2	Perlman syndrome (OMIM 267000)	AR	65%	Fetal ascites, neonatal demise, macrosomia, characteristic facial features, visceromegaly, DD/ID
FBXW7	FBXW7-related Wilms tumor ⁵	AD	Unknown	Adult-onset osteosarcoma (in 1 person); extrarenal rhabdoid (1 person); HL, FSGS, ovarian cystadenoma, & breast cancer (1 person) ⁶
GPC3 GPC4	Simpson-Golabi-Behmel syndrome type 1	XL	4%-9%	Macrosomia, macroglossia. DD/ID, multiple congenital anomalies, hepatoblastoma, neuroblastoma, gonadoblastoma, hepatocellular carcinoma, medulloblastoma.
KDM3B	KDM3B-related Wilms tumor ⁵	AD	<1%	In 1 person each: hepatoblastoma, AML, HL
MLH1 MSH2 MSH6 PMS2 ⁷	Constitutional mismatch repair deficiency (CMMRD) (See Lynch Syndrome.)	AR	<1%	Multiple tumor types; predominantly brain tumors & GI tumors
NYNRIN	NYNRIN-related Wilms tumor ⁵	AR	Unknown	Unknown
NSD1	Sotos syndrome	AD	<3%	Overgrowth, macrocephaly, DD/ID, leukemia, lymphoma, neuroblastoma, teratoma, & other cancer types.
PALB2	PALB2-related Fanconi anemia	AR	∼40%	Growth deficiency, multiple congenital anomalies, pigmentary abnormalities, medulloblastoma.
PIK3CA	PIK3CA-related overgrowth spectrum	Usually somatic mosaic	1%-2%	Disproportional overgrowth, brain malformations, DD/ID, lipomas, fibroadipose hyperplasia, vascular malformations
TP53	Li-Fraumeni syndrome	AD	<1%	Multiple cancers: breast, adrenal cortical carcinoma, osteosarcoma, medulloblastoma, choroid plexus carcinoma, rhabdomyosarcoma, hypodiploid ALL.
TRIM37	Mulibrey nanism syndrome (OMIM 253250)	AR	6%	IUGR, characteristic facial features, heart disease, skeletal anomalies
TRIP13	Mosaic variegated aneuploidy syndrome (OMIM 617598)	AR	~10%	Growth deficiency, microcephaly, dysmorphic features, DD/ID

Gene

Syndrome

MOI

Estimated Wilms Tumor Risk ¹

Other Clinical Features

AMER1 (WTX)

Osteopathia striata with cranial sclerosis

~5%

Sclerosis of cranium & long bones, macrocephaly, characteristic facial features, ±DD/ID

ASXL1

Bohring-Opitz syndrome

~7%

Growth deficiency, characteristic facial features, distinct posture, seizures. cardiac anomalies, DD/ID

BLM

Bloom syndrome

∼6%

Growth deficiency, immune deficiency, sun sensitivity, diabetes, multiple cancers

BRCA2

BRCA2-related Fanconi anemia

∼20%-60%

Growth deficiency, congenital anomalies, dysmorphic features, early-onset leukemia, medulloblastoma. pigmentary abnormalities

BUB1B

Mosaic variegated aneuploidy syndrome (OMIM 257300)

>85%

Growth deficiency, microcephaly, CNS anomalies, dysmorphic features, genitourinary anomalies, DD/ID, nephroblastoma, rhabdomyosarcoma, leukemia.

CDC73

CDC73-related disorders

∼3%

Hyperparathyroidism, parathyroid adenoma & cancer, osseous fibroma(s) of the jaw

CHEK2

CHEK2 cancer susceptibility (OMIM 609265)

∼3%

Breast cancer, ↑ risk of some additional cancers (prostate, GI, sarcomas, renal)

CTR9

Familial WT ²

>60%

Paternally inherited

DICER1

DICER1 tumor predisposition

<1% ³

Pleuropulmonary blastoma, pulmonary cysts, thyroid gland neoplasia, ovarian tumors, & cystic nephroma, ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma, pineoblastoma, pituitary blastoma

GLOW syndrome (See DICER1 Tumor Predisposition.)

Somatic mosaic / AD ⁴

Unknown; possibly >50%

GLOW; also macrocephaly, characteristic facial features, autism

DIS3L2

Perlman syndrome (OMIM 267000)

65%

Fetal ascites, neonatal demise, macrosomia, characteristic facial features, visceromegaly, DD/ID

FBXW7

FBXW7-related Wilms tumor ⁵

Unknown

Adult-onset osteosarcoma (in 1 person); extrarenal rhabdoid (1 person); HL, FSGS, ovarian cystadenoma, & breast cancer (1 person) ⁶

GPC3
GPC4

Simpson-Golabi-Behmel syndrome type 1

4%-9%

Macrosomia, macroglossia. DD/ID, multiple congenital anomalies, hepatoblastoma, neuroblastoma, gonadoblastoma, hepatocellular carcinoma, medulloblastoma.

KDM3B

KDM3B-related Wilms tumor ⁵

<1%

In 1 person each: hepatoblastoma, AML, HL

MLH1
MSH2
MSH6
PMS2 ⁷

Constitutional mismatch repair deficiency (CMMRD) (See Lynch Syndrome.)

<1%

Multiple tumor types; predominantly brain tumors & GI tumors

NYNRIN

NYNRIN-related Wilms tumor ⁵

Unknown

NSD1

Sotos syndrome

<3%

Overgrowth, macrocephaly, DD/ID, leukemia, lymphoma, neuroblastoma, teratoma, & other cancer types.

PALB2

PALB2-related Fanconi anemia

∼40%

Growth deficiency, multiple congenital anomalies, pigmentary abnormalities, medulloblastoma.

PIK3CA

PIK3CA-related overgrowth spectrum

Usually somatic mosaic

1%-2%

Disproportional overgrowth, brain malformations, DD/ID, lipomas, fibroadipose hyperplasia, vascular malformations

TP53

Li-Fraumeni syndrome

<1%

Multiple cancers: breast, adrenal cortical carcinoma, osteosarcoma, medulloblastoma, choroid plexus carcinoma, rhabdomyosarcoma, hypodiploid ALL.

TRIM37

Mulibrey nanism syndrome (OMIM 253250)

IUGR, characteristic facial features, heart disease, skeletal anomalies

TRIP13

Mosaic variegated aneuploidy syndrome (OMIM 617598)

~10%

Growth deficiency, microcephaly, dysmorphic features, DD/ID

From: Wilms Tumor Predisposition

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