Table 3.

Other Genes of Interest in the Differential Diagnosis of DICER1 Tumor Predisposition

Key Clinical Feature(s) Overlapping w/DICER1Gene(s)Differential DisorderMOIComment on Differential Disorder
Pneumothorax, pulmonary cysts, multinodular goiter, renal tumors FLCN Birt-Hogg-Dubé syndrome AD
  • Pneumothoraces typically in adulthood
  • Lung cysts usually bilateral & multifocal
  • Unclear whether MNG reported in assoc w/BHD is truly syndrome related
  • Renal tumors typically bilateral & multifocal; median age of diagnosis 48 yrs
  • Characteristic skin lesions (fibrofolliculomas, trichodiscomas, & acrochordons) appear in 3rd & 4th decades of life.
Lung cysts &/or pneumothorax CFTR Cystic fibrosis AR
  • Obstructive lung disease w/bronchiectasis
  • ↑ immunoreactive trypsinogen & sweat chloride
  • GI/nutritional abnormalities
  • Congenital absence of vas deferens
COL3A1 Vascular Ehlers-Danlos syndrome AD 1
  • Spontaneous &/or recurrent pneumothoraces
  • Vascular rupture/dissection
  • GI perforation or organ rupture
FBN1 Marfan syndrome AD
  • Recurrent pneumothorax associated w/lung bullae
  • Connective tissue findings
  • Ectopia lentis
  • Aortic root enlargement
SERPINA1 Alpha-1 antitrypsin deficiency AR
  • Chronic obstructive pulmonary disease (emphysema &/or chronic bronchitis), primarily in adults
  • Incidence of liver disease increases w/age
TSC1
TSC2 		Tuberous sclerosis complex AD
  • Lymphangioleiomyomatosis
  • Renal angiomyolipoma & cysts
Multinodular goiter, tumors FOXE1
HABP2
NKX2-1
SRGAP1 		Familial nonmedullary thyroid carcinoma (OMIM PS188550)ADAssoc w/multifocal & bilateral papillary thyroid carcinoma & multinodular goiter 2
PTEN PTEN hamartoma tumor syndrome ADPHTS assoc w/thyroid, breast, endometrial tumors & distinct mucocutaneous lesions
GNAS Fibrous dysplasia / McCune-Albright syndrome See footnote 3.
  • Thyroid lesions w/or w/o non-autoimmune hyperthyroidism
  • Café au lait macules, fibrous dysplasia, & other endocrinopathies
DUOX2
IYD
SLC5A5
TG
TPO
TSHR 		Thyroid dyshormonogenesis (OMIM 274400, 274500, 274700, 274800, 603372, 607200)ARFamilial MNG
APC APC-associated polyposis conditions AD
  • Cribriform-morular variant papillary thyroid cancer
  • Adenomatous colonic polyps, polyps of gastric fundus & duodenum, osteomas, dental anomalies, congenital hypertrophy
PRKAR1A Carney complex AD
  • Familial MNG, mostly nonfunctioning thyroid follicular adenomas
  • Skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, & schwannomas
TFAP2A Werner syndrome AD
  • MNG
  • No growth spurt during teen years; loss/graying of hair, hoarseness, scleroderma-like skin changes, bilateral cataracts, diabetes mellitus, hypogonadism, skin ulcers, & osteoporosis
Ovarian tumors SMARCA4
SMARCB1 		Rhabdoid tumor predisposition syndrome AD
  • Small cell carcinoma of the ovary, hypercalcemic type (malignant rhabdoid tumor of the ovary)
  • Rhabdoid tumor in kidney
  • Cancer in early childhood (age <5 yrs)
Renal cysts & cystic tumors DNAJB11
GANAB
PKD1
PKD2 		Autosomal dominant polycystic kidney disease AD
  • Multiple renal cysts
  • Liver cysts & ↑ risk of intracranial aneurysms
PKHD1 Autosomal recessive polycystic kidney disease AR
  • Multiple renal cysts
  • Biliary ductal ectasia & congenital hepatic fibrosis
VHL Von Hippel-Lindau syndrome AD
  • Multiple renal cysts & clear cell renal carcinoma
  • Hemangioblastomas, pheochromocytoma, pancreatic cysts, neuroendocrine tumors, endolymphatic sac tumors, epididymal & broad ligament cysts
WT1 4 Wilms tumor ADCystic renal tumors
Pineal gland tumors RB1 PineoblastomaADIntraocular retinoblastoma

AD = autosomal dominant; AR = autosomal recessive; BHD = Birt-Hogg-Dubé syndrome; GI = gastrointestinal; MNG = multinodular goiter; MOI = mode of inheritance

1.

Vascular Ehlers-Danlos syndrome is almost always inherited in an autosomal dominant manner, but rare examples of biallelic inheritance have been reported.

2.
3.

Fibrous dysplasia / McCune-Albright syndrome (FD/MAS) is not inherited. No parent of a child with FD/MAS has been demonstrated to have any significant, distinctive manifestations of the disorder. The risk to sibs is expected to be the same as in the general population. There are no verified instances of vertical transmission of FD/MAS.

4.

The most commonly reported germline genetic and epigenetic variants in individuals with Wilms tumor involve WT1 and the 11p15.5 locus. A growing number of variants in other genes have been reported.

From: DICER1 Tumor Predisposition

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