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Table 1 NF1-like syndromes

From: Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

DISEASE (OMIM/ORPHA ID [12, 13]) GENETIC BACKGROUND (INHERITANCE) REFERENCES
RASopathies (RAS/MAPK signaling pathway)
 Neurofibromatoses:   [7, 9, 14, 15]
 ° NF1 (OMIM 162200):
   • generalized/germline
   • segmental/mosaic/somatic
   • Watson sy.
    AD multiple CALMs
NF1 (AD)
 ° NF2 (OMIM 101000) NF2 (AD)
 ° Schwannomatosis (OMIM PS162091) LZTR1 (AD); NF2 (AD); SMARCB1 (AD)
Legius sy. (OMIM 611431) SPRED1 (AD) [7,8,9, 16,17,18,19]
Noonan sy. (OMIM PS163950) 50%: PTPN11 (AD); 13%: SOS1 (AD); 5%: RAF1 (AD); 5%: RIT1 (AD); < 5%: KRAS (AD); < 1%: BRAF (AD), LZTR1 (AR/AD), MRAS (AD), NRAS (AD), PPP1CB (AD), RRAS2 (AD), SHOC2 (AD), SOS2 (AD); 20%: unknown [7,8,9, 20]
LEOPARD sy. (OMIM PS151100) BRAF (AD); MAP2K1 (AD); PTPN11 (AD); RAF1 (AD) [7,8,9, 15, 21]
Noonan sy. with loose anagen hair (OMIM PS163950) SHOC2 (AD); PPP1CB (AD) [22, 23]
Cardiofaciocutaneous sy. (OMIM PS115150) BRAF (AD); KRAS (AD); MAP2K1 (AD); MAP2K2 (AD) [8, 9, 21]
Costello sy. (OMIM 218040) HRAS (AD) [8, 21]
CBL sy. (OMIM 165360) CBL (AD) [24]
Capillary malformation-arteriovenous malformation sy. (OMIM PS608354) EPHB4 (AD); RASA1 (AD) [25]
KITLG/c-KIT signaling pathway
Piebaldism (OMIM 172800) KIT (AD); SNAI2 (AD) [8, 15, 26]
Familial progressive hyperpigmentation sy. (OMIM 614233) KITLG (AD) [8, 26]
Familial progressive hyper- and hypopigmentation sy. (OMIM 145250)
PTEN hamartoma tumor syndromes
Proteus sy. (OMIM 176920) AKT1 (unknown) [15, 27]
Cowden sy. (OMIM PS158350) AKT1 (unknown); KLLN (unknown); PIK3CA (unknown); PTEN (AD); SEC23B (AD) [7, 9, 15, 28,29,30]
Peutz-Jeghers sy. (OMIM 175200) STK11 (AD) [15, 28]
Others
Ataxia-teleangiectasia (OMIM 208900) ATM (AR) [7, 9, 31]
Baraitser-Winter sy. (OMIM PS243310) ACTB (AD); ACTG1 (AD) [32,33,34]
Bloom sy. (OMIM 210900) RECQL3 (AR); TOP3A (AR) [7, 9, 35]
Carney complex OMIM type 1:160980; type 2:605244) type 1: PRKAR1A (AD); type 2: 2p16 (unknown) [9, 36]
CMMRD/DNA repair sys. (OMIM 276300) MLH1 (AR); MSH2 (AR); MSH6 (AR); PMS2 (AR) [7, 9, 15, 28]
Fanconi anaemia (OMIM PS227650) BRCA1 (AR); BRCA2 (AR); BRIP1 (unknown); ERCC4 (AR); FANCA (AR); FANCB (XLR); FANCC (AR); FANCD2 (AR); FANCE (AR); FANCF (unknown); FANCI (AR); MAD2L2 (AR); PALB2 (unkown); FANCL (AR); RAD51 (AD); RAD51C (AR); RFWD3 (AR); SLX4 (AR); UBE2T (AR); XRCC2 (AR); XRCC9 (unknown) [7, 9, 37]
 Fibromatoses /heterogenous group of multiple fibromas, most of them are benign/ unkown (possibly heterogenous, poligenic & multifactorial) [15]
Gaucher’s disease (OMIM type 1: 230800; type 2: 230900; type 3: 231000; type 3C: 231005; perinatal lethal: 608013) GBA (AR) [38]
Gorlin-Goltz sy. (OMIM 109400) PTCH1 (AD); PTCH2 (AD); SUFU (AD) [9, 39]
Jaffe-Campanacci sy. (ORPHA 2029) NF1 (AD); but mostly unknown [9]
 Johanson-Blizzard sy. (OMIM 243800) UBR1 (AR) [7, 40]
Kabuki sy. (OMIM PS147920) KDM6A (XLD); KMT2D (AD) [7, 41]
 Klippel-Trenaunay-Weber sy. (OMIM 149000) PIK3CA (unkown); but mostly unkown [15, 42]
 Lipomatoses /heterogenous group of multiple lipomas, they are nearly always benign/ unkown (possibly heterogenous, poligenic & multifactorial) [15]
 Marfan sy. (OMIM 154700) FBN1 (AD) [43]
Maternal UPD7p 7p (AD) [9]
 McCune-Albright sy. (OMIM 174800) GNAS (always de novo mosaicism) [7, 9, 15, 44]
MEN sys.:   [7, 9, 15, 45]
 ° MEN1 sy. (OMIM 131100) MEN1 (AD)
 ° MEN2A sy. (OMIM 171400) RET (AD)
 ° MEN2B sy. (OMIM 162300)
 Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) PCNT (AR) [7, 46]
Mosaic chromosomal tri−/monosomies (especially Turner sy.) heterogenous (usually de novo) [7, 9, 47]
 Multiple familial café-au-lait (ORPHA 2678) unknown (unknown) [7]
Neurocutaneous melanocytosis (ORPHA 2481) unknown (unknown) [15, 48]
Nijmegen breakage sy. (OMIM 251260) NBN (AR) [7, 9, 49]
Proteus-like sy. (ORPHA 2969) 50% PTEN (AD); 50% unknown (possibly PI3K pathway members’ mutations) [50]
Rapadilino sy. (OMIM 266280) RECQL4 (AR) [9]
Ring 7/11/12/15/17/22 chromosome sys. mostly de novo, but sometimes inherited (AD) [7, 9]
Rothmund-Thomson sy. (OMIM PS268400) type 1: ANAPC1 (AR); type 2: RECQL4 (AR) [9]
Rubinstein-Taybi sy. (OMIM PS180849) CREBBP (AD); EP300 (AD); del16p13.3 (unkown) [7, 51]
Silver-Russell sy. (OMIM 180860) 35–50% ICR1 hypomethylation; 7–10% maternal UPD7; rarely: del/dup/t of chr7/11p15.5, CDKN1C, IGF2, PLAG1, HMGA2; 40% unkown (always AD) [7, 9, 52]
Tuberous sclerosis (OMIM PS191100) IFNG (AD); TSC1 (AD); TSC2 (AD) [7, 9, 53]
von Hippel-Lindau sy. (OMIM 193300) CCND1 (AD); VHL (AD) [54]
  1. Disease names in bold: genetic conditions with increased tumor risk; disease names in italic: tumor predisposition with uncertain significance; Abbreviations: AR autosomal recessive, CBL sy. CBL gene mutation syndrome, chr chromosome, del deletion, dup duplication, ICR1 imprinting control region 1, OMIM/ORPHA ID Online Mendelian Inheritance in Man/Orphanet Identifier, p short arm of a chromosome, OMIM PS Phenotypic Series in Online Mendelian Inheritance in Man (similar phenotypes with heterogeneous genetic background), PI3K phosphoinositide-3-kinase-protein kinase, sy(s). syndrome(s), t translocation, UPD uniparental disomy