Table 1 NF1-like syndromes
From: Diagnostic difficulties and possibilities of NF1-like syndromes in childhood
GENETIC BACKGROUND (INHERITANCE) | REFERENCES | |
|---|---|---|
RASopathies (RAS/MAPK signaling pathway) | ||
 Neurofibromatoses: |  | |
 ° 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) | |
 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 | |
 LEOPARD sy. (OMIM PS151100) | BRAF (AD); MAP2K1 (AD); PTPN11 (AD); RAF1 (AD) | |
 Noonan sy. with loose anagen hair (OMIM PS163950) | SHOC2 (AD); PPP1CB (AD) | |
 Cardiofaciocutaneous sy. (OMIM PS115150) | BRAF (AD); KRAS (AD); MAP2K1 (AD); MAP2K2 (AD) | |
 Costello sy. (OMIM 218040) | HRAS (AD) | |
 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) | |
 Familial progressive hyperpigmentation sy. (OMIM 614233) | KITLG (AD) | |
 Familial progressive hyper- and hypopigmentation sy. (OMIM 145250) | ||
PTEN hamartoma tumor syndromes | ||
 Proteus sy. (OMIM 176920) | AKT1 (unknown) | |
 Cowden sy. (OMIM PS158350) | AKT1 (unknown); KLLN (unknown); PIK3CA (unknown); PTEN (AD); SEC23B (AD) | |
 Peutz-Jeghers sy. (OMIM 175200) | STK11 (AD) | |
Others | ||
 Ataxia-teleangiectasia (OMIM 208900) | ATM (AR) | |
 Baraitser-Winter sy. (OMIM PS243310) | ACTB (AD); ACTG1 (AD) | |
 Bloom sy. (OMIM 210900) | RECQL3 (AR); TOP3A (AR) | |
 Carney complex OMIM type 1:160980; type 2:605244) | type 1: PRKAR1A (AD); type 2: 2p16 (unknown) | |
 CMMRD/DNA repair sys. (OMIM 276300) | MLH1 (AR); MSH2 (AR); MSH6 (AR); PMS2 (AR) | |
 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) | |
 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) | |
 Jaffe-Campanacci sy. (ORPHA 2029) | NF1 (AD); but mostly unknown | [9] |
 Johanson-Blizzard sy. (OMIM 243800) | UBR1 (AR) | |
 Kabuki sy. (OMIM PS147920) | KDM6A (XLD); KMT2D (AD) | |
 Klippel-Trenaunay-Weber sy. (OMIM 149000) | PIK3CA (unkown); but mostly unkown | |
 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) | |
 MEN sys.: |  | |
 ° 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) | |
 Mosaic chromosomal tri−/monosomies (especially Turner sy.) | heterogenous (usually de novo) | |
 Multiple familial café-au-lait (ORPHA 2678) | unknown (unknown) | [7] |
 Neurocutaneous melanocytosis (ORPHA 2481) | unknown (unknown) | |
 Nijmegen breakage sy. (OMIM 251260) | NBN (AR) | |
 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) | |
 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) | |
 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) | |
 Tuberous sclerosis (OMIM PS191100) | IFNG (AD); TSC1 (AD); TSC2 (AD) | |
 von Hippel-Lindau sy. (OMIM 193300) | CCND1 (AD); VHL (AD) | [54] |