Table S1: List of the 646 known pathogenic targeted in the present study and their associated mode of inheritance. ARID: autosomal-recessive intellectual disability; ADID: autosomal-dominant intellectual disability; XLID: X-linked intellectual disability.

ABAT ARID ASCL1 ARID CACNG2 ADID ABCD1 XLID ASNS ARID CAPN10 ARID ABRA ARID ASPA ARID CASC5 ARID ACBD6 ARID ASPM ARID CASK XLID ACSL4 XLID ASXL1 ADID CASP2 ARID ACTB XLID ASXL3 ADID CBL ADID ACTG1 XLID ATM ARID CBS ARID ACY1 ARID ATP5A1 ARID CC2D1A ARID ADAR ARID ATP6AP2 XLID CC2D2A ARID ADAT3 ARID ATP6V0A2 ARID CCDC22 XLID ADD3 ARID ATP7A XLID CCDC28B ARID ADK ARID ATP8A2 ARID CCDC88C ARID ADRA2B ARID ATR ARID CCNA2 ARID ADSL ARID ATRX XLID CDC6 ARID AGAP1 ADID ATXN1 ADID CDH15 ADID AHI1 ARID B3GALNT2 ARID CDK19 ADID AIMP1 ARID B3GALTL ARID CDK5RAP2 ARID AIPL1 ARID B3GNT1 ARID CDK6 ARID AKT3 ADID B4GALT1 ARID CDKL5 XLID ALDH7A1 ARID B9D1 ARID CDKN1C ADID ALG1 ARID B9D2 ARID CDT1 ARID ALG11 ARID BBIP1 ARID CECR2 ADID ALG12 ARID BBS1 ARID CELF4 ADID ALG13 XLID BBS10 ARID CENPJ ARID ALG2 ARID BBS12 ARID CEP135 ARID ALG3 ARID BBS2 ARID CEP152 ARID ALG6 ARID BBS4 ARID CEP290 ARID ALG8 ARID BBS5 ARID CEP41 ARID ALG9 ARID BBS7 ARID CEP63 ARID AMPD2 ARID BBS9 ARID CEP89 ARID AMT ARID BCAP31 XLID CHD2 ADID ANK3 ARID BCOR XLID CHD7 ADID ANKRD11 ADID BLM ARID CHMP1A ARID AP1S2 XLID BOLA3 ARID CHN1 ADID AP3B1 ARID BRAF ADID CLCN4 XLID AP4B1 ARID BRD2 ADID CLIC2 XLID AP4E1 ARID BRD3 ADID CLIP2 ARID AP4M1 ARID BRWD3 XLID CLN3 ARID AP4S1 ARID BSCL2 ARID CLN5 ARID ARFGEF2 ARID BUB1B ARID CLN6 ARID ARHGEF6 XLID C11orf46 ARID CLN8 ARID ARHGEF9 XLID C12orf57 ARID CNKSR1 ARID ARID1A ADID C2ORF86 ARID CNKSR2 XLID ARID1B ADID C3orf58 ADID CNTN2 ARID ARL13B ARID C5orf42 ARID CNTN4 ADID ARL6 ARID C8orf41 ARID CNTNAP2 ARID ARNT2 ARID C9orf86 ARID COASY ARID ARSA ARID CA8 ARID COG1 ARID ARX XLID CACNA1G ARID COG4 ARID COG5 ARID EP300 ADID GRIN2A ADID COG6 ARID EPB41L1 ADID GRIN2B ADID COG7 ARID ERCC1 ARID GTF2I ADID COG8 ARID ERCC4 ARID HCCS XLID COQ5 ARID ERLIN2 ARID HCFC1 XLID COX7B XLID ESCO2 ARID HDAC4 ADID CRADD ARID EVC2 ARID HDAC8 XLID CRBN ARID EXOC4 ARID HEPACAM XLID CREBBP ADID EXOSC3 ARID HERC2 ARID CSPP1 ARID EYA1 ADID HESX1 ADID CTCF ADID EZH2 ADID HEXA ARID CTNNB1 ADID FAM126A ARID HIP1 ADID CTSD ARID FAM58A XLID HIST1H4B ARID CUL4B XLID FANCB XLID HIST3H3 ARID DAG1 ARID FASN ARID HOXA1 ARID DARS ARID FAT4 ARID HPRT1 XLID DCHS1 ARID FBXL4 ARID HRAS ADID DCX XLID FGD1 XLID HSD17B10 XLID DDOST ARID FIG4 ARID HSPD1 ARID DDX11 ARID FKRP ARID HUWE1 XLID DEAF1 ADID FKTN ARID IDS XLID DHCR24 ARID FLNA XLID IER3IP1 ARID DHCR7 ADID FMN2 ARID IGBP1 XLID DLG3 XLID FMR1 XLID IGF1R ADID DLK1 ADID FOLR1 ARID IKBKG XLID DNM2 ARID FOXG1 ADID IL1RAPL1 XLID DNMT1 ADID FOXP1 ADID INO80 ARID DNMT3A ADID FOXP2 ADID INPP4A ARID DNMT3B ARID FRY ARID INPP5E ARID DOCK8 ADID FTSJ1 XLID IQSEC2 XLID DOLK ARID GAD1 ARID ISPD ARID DPAGT1 ARID GALC ARID JAG1 ADID DPM1 ARID GAMT ARID JARID2 ADID DPM2 ARID GATAD2B ADID JHDM1D ADID DPM3 ARID GATM ARID JMJD1C ADID DYNC1H1 ADID GCSH ARID KANK1 ADID DYRK1A ADID GDI1 XLID KANSL1 ADID EBP XLID GFAP XLID KAT6A ADID EEF1B2 ARID GJC2 ARID KAT6B ADID EFTUD2 XLID GK XLID KCNJ10 ARID EHMT1 ADID GLDC ARID KCNK9 ADID EIF2B1 ARID GLI3 ADID KCNQ2 ADID EIF2B2 ARID GLIPR1 ARID KCNT1 ADID EIF2B3 ARID GMPPA ARID KCTD13 ADID EIF2B4 ARID GNAO1 ADID KDM5A ARID EIF2B5 ARID GON4L ARID KDM5C XLID EIF2S3 XLID GPC3 XLID KDM6A XLID EIF4A3 ARID GPD2 ARID KDM6B ARID ELF2 ADID GPR56 ARID KIAA0196 ARID ELOVL4 ARID GRIA3 XLID KIAA1279 ARID ELP2 ARID GRID2 ARID KIAA2022 XLID ENOSF1 ARID GRIK2 ARID KIF11 XLID ENTPD1 ARID GRIN1 ADID KIF1A ADID KIF2A ADID MPDZ ARID PEX13 ARID KIF5C ADID MPI ARID PEX14 ARID KIF7 ARID MTHFR ARID PEX16 ARID KIRREL3 ADID MTOR ADID PEX19 ARID KLF8 XLID MTR ARID PEX2 ARID KLHL15 XLID MYCN ADID PEX26 ARID KDM2A ADID MYOCD ARID PEX3 ARID KMT2C ADID NAA10 XLID PEX5 ARID KMT2D ADID NAGLU ARID PEX6 ARID KPTN ARID NALCN ARID PEX7 ARID KRAS ADID NDE1 ARID PGAP2 ARID L1CAM XLID NDP XLID PGAP3 ARID L2HGDH ARID NDST1 ARID PGK1 XLID LAMA1 ARID NDUFA1 XLID PGM1 ARID LAMC1 ADID NFIX ADID PHC1 ARID LAMP2 XLID NHS XLID PHF21A ADID LARGE ARID NID1 ADID PHF6 XLID LARP7 ARID NIN ARID PHF8 XLID LAS1L XLID NIPBL ADID PIGA XLID LIAS ARID NLGN3 XLID PIGN ARID LIG4 ADID NLGN4X XLID PIGW ARID LIMS1 ADID NLRP2 ADID PIK3CA ADID LINS ARID NLRP7 ADID PIK3R2 XLID LRP2 ARID NPHP1 ARID PLCB1 ARID LYRM7 ARID NR1I3 ADID PLP1 XLID MACROD2 ADID NRAS ADID PMM2 ARID MAGEL2 ADID NRXN1 ARID PNKP ARID MAN1B1 ARID NSD1 ADID PNPO ARID MAOA XLID NSDHL XLID PNPT1 ARID MAOB XLID NSUN2 ARID POLG ARID MAP2K1 XLID OCLN ARID POLR3B ARID MAP2K2 XLID OCRL XLID POMGnT1 ARID MBD5 ADID OFD1 XLID POMK ARID MBTPS2 XLID OPHN1 XLID POMT1 ARID MCPH1 ARID ORC1 ARID POMT2 ARID MECP2 XLID ORC4 ARID PORCN XLID MED12 XLID ORC6 ARID PPT1 ARID MED13L ADID OSTM1 ARID PQBP1 XLID MED17 ARID OTC XLID PRKCG ARID MED23 ARID PACS1 ADID PRKRA ARID MEF2C ADID PAFAH1B1 ADID PRMT10 ARID MFSD8 ARID PAK3 XLID PRMT7 ARID MGAT2 ARID PARP1 ARID PRPS1 XLID MID1 XLID PCDH19 XLID PRRT2 ARID MID2 XLID PCNT ARID PRSS12 ARID MKKS ARID PDE4D ADID PSAP ARID MKL1 ARID PDE6D ARID PTCH1 ADID MKL2 ARID PDHA1 XLID PTCHD1 XLID MKS1 ARID PDHX ARID PTEN ADID MKS1 ARID PECR ARID PTPN11 ADID MLC1 ARID PEX1 ARID PUF60 ADID MOGS ARID PEX10 ARID RAB18 ARID MPDU1 ARID PEX12 ARID RAB36 ARID RAB39B XLID SLC25A19 ARID TBC1D24 ARID RAB3GAP1 ARID SLC25A22 ARID TBC1D32 ADID RAB3GAP2 ARID SLC25A5 XLID TBC1D7 ARID RAD21 ADID SLC2A1 ADID TBX1 ADID RAI1 ADID SLC31A1 ARID TCF4 ADID RALGDS ARID SLC33A1 ARID TCTN1 ARID RANBP2 ADID SLC35A1 ARID TCTN2 ARID RARS2 ARID SLC35A2 XLID TCTN3 ARID RBBP8 ARID SLC35A3 ARID TECR ARID RBM10 XLID SLC35C1 ARID TH ARID RELN ARID SLC4A4 ARID THOC2 XLID RFT1 ARID SLC6A8 XLID THOC6 ARID RGS7 ARID SLC9A6 XLID TIMM8A XLID RIT1 ADID SLITRK1 ADID TM4SF20 ADID RMND1 ARID SMARCA2 ADID TMCO1 ARID RNASEH2A ARID SMARCA4 ADID TMEM135 ARID RNASEH2B ARID SMARCB1 ADID TMEM138 ARID RNASEH2C ARID SMARCE1 ADID TMEM165 ARID RNF168 ARID SMC1A XLID TMEM216 ARID RPGRIP1L ARID SMC3 ADID TMEM231 ARID RPL10 XLID SMS XLID TMEM237 ARID RPS6KA3 XLID SNAP29 ARID TMEM5 ARID RTTN ARID SNX27 ARID TMEM67 ARID SALL1 ADID SOS1 ADID TMPRSS4 ARID SALL4 ADID SOX10 ADID TNK2 ARID SAMHD1 ARID SOX2 ADID TRAPPC9 ARID SATB2 ADID SOX3 XLID TREX1 ARID SCAPER ARID SOX5 ADID TRIM32 ARID SCLT1 ADID SOX9 ADID TRIM32 ARID SCN1A ADID SPTAN1 XLID TRIO ADID SCN2A ADID SRCAP ADID TRMT1 ARID SCN8A ADID SRD5A3 ARID TRMT10A ARID SCRIB ADID SRF ARID TSC1 ADID SEMA3E ADID SRPX2 XLID TSC2 ADID SEPSECS ARID SSR4 XLID TSEN2 ARID SERPINA7 XLID ST3GAL3 ARID TSEN34 ARID SETBP1 ADID ST3GAL5 ARID TSEN54 ARID SETD2 ADID STAG2 XLID TSPAN7 XLID SETD5 ADID STAMBP ARID TTC21B ARID SETMAR ARID STIL ARID TTC8 ARID SGK196 ARID STT3A ARID TTI2 ARID SHANK3 ADID STT3B ARID TUBA1A ADID SHH ADID STXBP1 ARID TUBA8 ARID SHOC2 ARID SUMF1 ARID TUBB2B ADID SHROOM4 XLID SURF1 ARID TUBB3 ADID SIK1 ADID SYN1 XLID TUBB4A ADID SIM2 ADID SYNGAP1 ADID TUBG1 ADID SIX3 ARID SYP XLID TUBGCP6 ARID SIX5 ARID SZT2 ARID TUSC3 ARID SKI ADID TAF1 XLID TWIST1 ADID SLC12A2 ADID TAF2 ARID UBE2A XLID SLC16A2 XLID TAF6 ARID UBE3A ADID SLC19A3 ARID TBC1D20 ARID UBR7 ARID UPF3B XLID WWOX ARID ZDHHC9 XLID VLDLR ARID XYLT1 ARID ZEB2 ADID VPS13B ARID ZBTB18 ADID ZIC2 XLID VRK1 ARID ZBTB20 ADID ZNF335 ARID WAC ADID ZBTB40 ARID ZNF423 ARID WDR45 XLID ZC3H14 ARID ZNF526 ARID WDR45L ARID ZC4H2 XLID ZNF711 XLID WDR62 ARID ZCCHC8 ARID WDR81 ARID ZDHHC15 XLID

.

Table S2: List of the 610 candidate genes targeted in the present study.

AGO1 BRE CREB1 ENY2 HAT1 ACTL6A BRPF1 CSMD1 EP400 HDAC1 ACTL6B BRPF3 CSNK2A1 EPC1 HDAC10 ADNP2 BRWD1 CSRP2BP EPC2 HDAC11 ADRB2 BTG1 CTCFL EPHA7 HDAC2 AEBP2 BTG2 CTNND2 ERBB4 HDAC3 ALKBH8 BZRAP1 CTR9 ESCO1 HDAC5 AMIGO2 C11ORF30 CTXN1 ETF1 HDAC6 ANKRA2 C14ORF169 CUX2 EXOC6B HDAC7 ANKRD12 C17ORF49 CXORF36 EYA2 HDAC9 APBA1 C2ORF86 CXXC1 EYA3 HENMT1 APBB1 CA6 DAB1 EZH1 HES1 APPL1 CABIN1 DAPK1 FAAH2 HEY2 APPL2 CACNA1D DAPK3 FAM175A HIC1 ARHGAP15 CACNA1F DBX2 FAM48A HIF1A ARHGAP32 CACNA1H DCDC2 FAM65A HINFP ARID2 CADM1 DDX17 FAT1 HIRA ARID3B CADPS2 DEK FBXO11 HIVEP2 ARID4B CAMK2G DGAT2 FBXO40 HLTF ARIH1 CAMTA2 DGCR8 FHIT HMG20A ARL6 CARM1 DISC1 FLYWCH2 HMG20B ARRB1 CBX1 DLG1 FOS HMGN2 ASCC3 CBX2 DLG2 FOXA2 HMGN3 ASF1A CBX4 DLG4 FOXA3 HNRNPU ASF1B CBX5 DLX1 FTSJ2 HOXB2 ASH1L CBX6 DLX2 FTSJ3 HS3ST1 ASH2L CBX7 DMAP1 FTSJD2 HS6ST2 ASTN2 CBX8 DNAJC2 GABRA4 HTR1B ASZ1 CCDC101 DNER GABRB1 HTR2A ATF2 CCDC28B DNM3 GABRB3 HTR3A ATF7IP CDH10 DNMT3L GABRD HTR3C ATXN7L3 CDH11 DOT1L GALNT13 HTR7 AURKA CDH18 DPF3 GATAD2A ICMT AURKB CDH2 DPP10 GFI1B ID1 AVPR1A CDH6 DPP6 GMNN IKZF1 BABAM1 CDH9 DPY30 GPC1 ING2 BANP CDYL DR1 GPR6 ING3 BAZ1A CDYL2 DRD1 GRIA2 ING4 BAZ1B CEBPB DRD2 GRID2 ING5 BAZ2A CHD1 DRD3 GRIK1 ISL1 BAZ2B CHD3 DRD4 GRM3 ITGAX BCORL1 CHD4 DSCAM GRM5 ITGB1 BDNF CHD5 EDF1 GRM7 KDM8 BHLHE41 CHD6 EED GRM8 JMJD6 BHMT CHD8 EEF2K GRPR KANSL2 BMI1 CHD9 EFEMP1 GRTP1 KANSL3 BMP4 CHL1 EGR1 GSK3A KAT2A BPTF CHMP1B EHMT2 GSPT1 KAT2B BRD1 CIR1 EID1 GTF2IRD1 KAT5 BRD4 CLOCK ELP3 GTF3C4 KAT7 BRD7 CNR1 EMID2 H2AFY KAT8 BRD8 CRABP1 EN2 H2AFY2 KDM1A KDM1B MLH1 NTRK2 RAB6A SHANK2 KDM2B KMT2C NTRK3 RAPGEF4 SIM1 KDM3A MLL5 NUDT21 RASGEF1B SIN3A KDM3B MORF4L1 OGT RB1CC1 SIN3B KDM4A MORF4L2 OLIG1 RBBP4 SIRT1 KDM4B MPHOSPH8 OPRM1 RBBP5 SIRT2 KDM4C MRGBP OXTR RBBP7 SIRT6 KDM4D MSH2 PADI4 RBFOX1 SKP1 KDM4DL MSL1 PAF1 RBL1 SLC25A12 KDM5B MSL2 PAK1 RBL2 SLC4A10 KPNA2 MSL3 PAX5 RCBTB1 SLC6A1 L3MBTL MTA1 PAXIP1 RCOR1 SLC6A3 L3MBTL2 MTA2 PBRM1 RERE SLC6A4 L3MBTL3 MTF1 PCDH10 REST SLC9A9 L3MBTL4 MYB PCDH11X RFWD2 SLITRK2 LARP6 MYSM1 PCDH8 RFX4 SLITRK4 LCMT1 MYT1 PCDH9 RGS6 SMARCA5 LEO1 NAA60 PCGF1 RHOF SMARCAD1 LIN7A NAB2 PCNA RIMS3 SMARCC1 LIX1 NAV2 PER1 RING1 SMARCC2 LMX1A NCAM2 PHB RNF2 SMARCD1 LRFN5 NCOA1 PHF1 RNF20 SMARCD2 LRWD1 NCOA2 PHF13 RNF40 SMARCD3 LYNX1 NCOA6 PHF15 RNF8 SMYD2 MAEL NCOR1 PHF16 ROBO1 SMYD3 MAGEA1 NCOR2 PHF17 RORB SP1 MAGEA2B NDN PHF20 RPS6KA5 SP2 MAP2 NDNL2 PICK1 RSF1 SP5 MAP2K3 NEFH PITX1 RUVBL1 SPEN MAP3K7 NEK6 PKN1 RUVBL2 SPOCK1 MAPK10 NELL2 PKN2 RYBP SRFBP1 MAPK8 NENF PLD6 SALL2 SS18L1 MAPRE3 NGF POLE3 SALL3 STAG1 MARCKS NKAIN2 POLE4 SAP130 STK24 MARK1 NKX3-1 PON1 SAP18 STMN2 MBD1 NLGN1 PPARGC1B SAP30 STX1A MBD2 NNAT PRDM1 SATB1 SUDS3 MBD3 NOTCH1 PRDM6 SCRIB SUPT16H MBD4 NPAS2 PRDM9 SDC3 SUPT3H MBD6 NPTX1 PRKAA1 SEMA4C SUPT7L MBTD1 NR2C1 PRKAA2 SEMA5A SUV39H1 MCRS1 NR2E1 PRKCB SEMA6B SUV39H2 MDGA2 NRCAM PRKG2 SERPINI1 SUV420H1 MEAF6 NRG1 PRMT2 SETD1A SUV420H2 MECOM NRG4 PRMT3 SETD1B SUZ12 MED13 NRIP1 PRMT5 SETD3 SYCP1 MED24 NRP1 PRMT6 SETD4 SYN2 MEF2B NRP2 PRMT8 SETD6 SYNCRIP MEF2D NTAN1 PTF1A SETD7 SYT1 METTL11A NTF3 PTPRN2 SETD8 TADA1 METTL14 NTM PTPRT SETDB1 TADA2A METTL3 NTN1 PYGO2 SETDB2 TADA2B MGEA5 NTN4 RAB3A SEZ6L2 TAF10 MGLL NTNG1 RAB3B SF3B1 TAF12 MKRN3 NTRK1 RAB3D SH3BGRL2 TAF1L TAF4 WHSC1 TAF5 WHSC1L1 TAF5L NELFA TAF6L WSB1 TAF7 YEATS2 TAL1 YEATS4 TBL1X YWHAB TBL1XR1 YWHAE TCF21 YWHAH TDRD1 YY1 TDRD3 ZBTB7A TDRD5 ZDHHC14 TDRD9 ZFHX4 TET1 ZMYM3 TFAP4 ZMYND15 THBD ZMYND8 TLE3 ZNF217 TLK1 ZNF347 TLK2 ZNF385B TMEM195 ZNF721 TMEM66 ZNF804A TMOD2 TNFRSF19 TOP2A TOP2B TOPBP1 TRAF6 TRIM45 TRMT112 TRPC5 TRRAP TSPYL2 UBAC2 UBAP2L UBE2B UBE2E1 UBE2H UBE2N UBN1 UBR2 UHRF1BP1 UNC5A USF1 USP16 USP21 USP22 USP3 UTP3 VPS72 VSNL1 WDR13 WDR5 WDR7 WDR8 WDR82 Table S3: Selection of variants of unknown or probably benign significance. See the text for further commentaries.

Genomic Patient position (hg19) transcript coding Inheritance 6 ASCC3 chr6:101215152 NM_006828 c.1464dupC p.Tyr489LeufsTer5 de novo 12 CACNA1H chr16:1254396 NM_021098.2 c.2389C>T p.Arg797Cys de novo 37 CTCFL chr20:56098868 NM_001269043.1 c.394C>T p.Gln132Ter de novo 38 HUWE1 chrX:53674318 NM_031407.6 c.344C>T p.Ser115Phe de novo 39 PDE4D chr5:58571162 NM_001197220 c.65+2T>A splicing? de novo 40 C22orf39 chr22:19434960 NM_173793.4 c.244T>C p.Trp82Arg de novo 41 NLGN4X chrX:5821346 NM_181332.2 c.1361_1372del12 p.Val454_Ala457del de novo 42 BCOR chrX:39911649 NM_001123385.1 c.4981C>T p.Arg1661Ter maternal (X-linked) 43 SHROOM4 chrX:50376558 NM_020717.3 c.2512_2514delCAT p.His838del maternal (X-linked) 44 MECP2 chrX:153296087 NM_001110792.1 c.1164_1172del9 + p.Lys389_Pro391del+ maternal (X-linked) c.1191_1202del12 + Leu398_Pro401del + c.1219_1227del9 Ser407_Glu409del

Table S4: Main clinical characteristics of the patients with pathogenic or probably pathogenic variants, as well as some variants of unknown clinical consequence.

DECIPHER Chr. Patient Gene HGVS code Genotype Phenotype ID sex

Abnormality of the genitourinary system, Blepharophimosis, Brachycephaly, Depressed nasal bridge, Growth delay, 1 323184 46XY MED12 chrX:g.70341452G>A Hemizygous Hypertonia, Intellectual disability, Microcephaly, Microretrognathia, Muscular , Postnatal growth retardation

Abnormality of the fontanelles or cranial sutures, Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Decreased body weight, Downslanted 2 325600 46XX NFIX chr19:g.13201182CT>C Heterozygous palpebral fissures, Feeding difficulties, Feeding difficulties in infancy, Hearing impairment, Intellectual disability, Intrauterine growth retardation, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Prominent forehead, Short stature

Abnormality of the nose, Aggressive behavior, Delayed speech and language development, Hypertelorism, Hypertonia, 3 325597 46XX CASK chrX:g.41413142A>C Heterozygous Intellectual disability, Intrauterine growth retardation, Low-set ears, Microcephaly, Micrognathia, Motor delay, Muscular hypotonia, Stereotypic behavior

Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, 4 325593 46XX NIPBL chr5:g.37024800CAAT>C Heterozygous Delayed speech and language development, Facial asymmetry, Hyperactivity, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Microcephaly, Synophrys, Upslanted palpebral fissure Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the skeletal system, Anteverted ears, Autistic 5 325592 46XY KMT2D chr12:g.49434956GA>G Heterozygous behavior, Decreased body weight, Delayed speech and language development, Feeding difficulties, Hearing impairment, Intellectual disability, Macrotia, Low-set ears, Mandibular prognathia, Microcephaly, Motor delay, Muscular hypotonia, Short stature, Stereotypic behavior

Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Aggressive behavior, Anteverted ears, Decreased body weight, Delayed closure of the anterior fontanelle, Delayed speech and language development, Epicanthus, Hypermetropia, 6 325587 46XY RPS6KA3 chrX:g.20222209T>A Hemizygous Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Macrotia, Long eyebrows, Low anterior hairline, Low-set ears, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Short palm, Short stature, Sleep disturbance, Tapered finger, Thick vermilion border

Abnormality of the hand, Abnormality of the head, Abnormality of the mouth, Abnormality of the palate, Autistic behavior, Delayed 7 325604 46XY SLC16A2 chrX:g.73744262C>T Hemizygous speech and language development, Epicanthus, Hypertelorism, Intellectual disability, Motor delay, Muscular hypotonia, Neonatal hypotonia, Nystagmus, Sleep disturbance

Gait disturbance, Happy demeanor, Intellectual disability, 8 325572 46XY UBE3A chr15:g.25584294C>T Heterozygous Microcephaly, Poor speech

Severe intellectual disability, Seizures, Spasticity, Atrophy of 9 325580 46XY NSDHL chrX:g.152031180G>A Hemizygous optic discs, Microcephaly, Plagiocephaly, Skeletal abnormalities, High nasal bridge, Strabismus, Micrognathia Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the male genitalia, Abnormality of the 10 325573 46XY TAF1 chrX:g.70612503G>C Hemizygous skeletal system, Decreased body weight, Intrauterine growth retardation, Low-set ears, Microcephaly, Motor delay, Pierre- Robin sequence, Strabismus

Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the hand, Abnormality of the nose, Abnormality of the palate, Abnormality of the skeletal system, 11 325585 46XX SMC3 chr10:g.112356156G>A Heterozygous Facial asymmetry, Feeding difficulties, Hearing impairment, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Long eyebrows, Low-set ears, Microcephaly, Neonatal hypotonia, Synophrys

Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Delayed speech and 12 325589 46XX DYRK1A chr21:g.38858852ACAGAT>A Heterozygous language development, Downslanted palpebral fissures, Hypertelorism, Intellectual disability, Low-set ears, Microcephaly, Micrognathia, Motor delay, Short stature, Stereotypic behavior, Symptomatic seizures

Abnormality of the cardiovascular system, Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the mouth, Abnormality of the philtrum, Abnormality of the skeletal 13 325590 46XY SETBP1 chr18:g.42531917T>C Heterozygous system, Decreased body weight, Feeding difficulties in infancy, Hearing impairment, Hypertonia, Intellectual disability, Low-set ears, Microcephaly, Micrognathia, Motor delay, Muscular hypotonia, Short stature, Symptomatic seizures

Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the nose, Decreased body weight, 14 325595 46XX PTPN11 chr12:g.112888166A>G Heterozygous Downslanted palpebral fissures, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Macrocephaly, Motor delay, Muscular hypotonia, Prominent forehead, Short stature, Symptomatic seizures

Abnormality of the cardiovascular system, Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Aggressive behavior, Decreased body weight, Delayed speech 15 325599 46XY KMT2A chr11:g.118373140T>TA Heterozygous and language development, Downslanted palpebral fissures, Feeding difficulties, Hypertelorism, Hypertrichosis, Intellectual disability, Low-set ears, Microcephaly, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Posteriorly rotated ears, Short stature, Telecanthus

Aggressive behavior, Autism spectrum disorder, Decreased body weight, Depressed nasal bridge, Downslanted palpebral 16 323183 46XY MED13L chr12:g.116413012C>T Heterozygous fissures, Hearing impairment, Intellectual disability, Low-set ears, Muscular hypotonia

Dental crowding, Depressed nasal bridge, Downslanted palpebral fissures, Intellectual disability, Low-set ears, 17 323185 46XY MED13L chr12:g.116440853G>A Heterozygous Moderately short stature, Muscular hypotonia, Prominent forehead, Unilateral renal agenesis

Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Anteverted ears, chrX:g.44929156TCAGATGA Decreased body weight, Delayed speech and language 18 325608 46XY KDM6A Hemizygous CGG>T development, Epicanthus, Hyperactivity, Intellectual disability, Low-set ears, Microcephaly, Motor delay, Myopia, Short stature, Strabismus

Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, 19 325609 46XX ZBTB20 chr3:g.114058246C>G Heterozygous Abnormality of the skeletal system, Abnormality of the teeth, Agenesis of corpus callosum, Aggressive behavior, Anteverted ears, Autistic behavior, Delayed speech and language development, Downslanted palpebral fissures, Epicanthus, Feeding difficulties, Hypertelorism, Hypertrichosis, Intellectual disability, Macrocephaly, Motor delay, Muscular hypotonia, Prominent forehead, Sleep disturbance, Strabismus

Abnormality of the mouth, Abnormality of the nose, Abnormality of the skeletal system, Aggressive behavior, Anteverted ears, Decreased body weight, Delayed speech and language 20 325574 46XX NDST1 chr5:g.149921213G>A Homozygous development, Developmental regression, Hyperactivity, Hypertelorism, Hypertonia, Intellectual disability, Motor delay, Muscular hypotonia, Stereotypic behavior, Symptomatic seizures

Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the teeth, Delayed speech and language development, 21 325575 46XX KCNT1 chr9:g.138671275G>A Heterozygous Hypertrichosis, Intellectual disability, Microcephaly, Motor delay, Muscular hypotonia, Sleep disturbance, Stereotypic behavior, Strabismus, Symptomatic seizures

Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Decreased body weight, Delayed speech and language development, Feeding difficulties, 22 325583 46XX ARID1B chr6:g.157522469C>T Heterozygous Feeding difficulties in infancy, Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Micrognathia, Motor delay, Muscular hypotonia, Myopia, Neonatal hypotonia, Short stature, Upslanted palpebral fissure

Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the palate, Abnormality of the skeletal system, 23 325586 46XX KMT2D chr12:g.49445935GT>G Heterozygous Abnormality of the teeth, Autistic behavior, Facial asymmetry, Hearing impairment, Hypertrichosis, Intellectual disability, Macrotia, Low-set ears, Microcephaly, Motor delay, Muscular hypotonia, Stereotypic behavior Abnormality of the hair, Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the mouth, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Anteverted ears, Autistic behavior, Delayed speech and language development, Facial 24 325572 46XY ANKRD11 chr16:g.89349577CCTCA>C Heterozygous asymmetry, Feeding difficulties, Hyperactivity, Hypertelorism, Intellectual disability, Intrauterine growth retardation, Long eyebrows, Low-set ears, Macrocephaly, Motor delay, Muscular hypotonia, Neonatal hypotonia, Prominent forehead, Stereotypic behavior, Synophrys, Upslanted palpebral fissure

Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the philtrum, Anteverted ears, Decreased body 25 325603 46XY RAD21 chr8:g.117878901C>T Heterozygous weight, Delayed speech and language development, Intellectual disability, Intrauterine growth retardation, Macrotia, Long eyebrows, Low-set ears, Microcephaly, Myopia

Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Aggressive behavior, Delayed 26 325606 46XX KMT2A chr11:g.118376288TC>T Heterozygous speech and language development, Epicanthus, Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Macrotia, Microcephaly, Posteriorly rotated ears, Short stature, Strabismus, Synophrys

Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the teeth, Anteverted ears, Delayed chr18:g.59774054G>A + speech and language development, Epicanthus, Increased body 27 325577 46XY PIGN Heterozygous chr18:g.59828492AT>A weight, Intellectual disability, Motor delay, Muscular hypotonia, Neonatal hypotonia, Stereotypic behavior, Symptomatic seizures, Tall stature

Abnormality of the cardiovascular system, Abnormality of the 28 325584 46XY KMT2D chr12:g.49431178G>A Heterozygous fontanelles or cranial sutures, Abnormality of the hand, Abnormality of the nose, Abnormality of the palate, Decreased body weight, Feeding difficulties, Intellectual disability, Intrauterine growth retardation, Micrognathia, Motor delay, Muscular hypotonia, Neonatal hypotonia, Short stature, Upslanted palpebral fissure

Abnormality of the cardiovascular system, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Agenesis of corpus callosum, Aggressive behavior, Decreased body weight, Delayed speech 29 325582 46XX ARID1A chr1:g.27056169A>T Heterozygous and language development, Facial asymmetry, Feeding difficulties, Hypertonia, Hypertrichosis, Intellectual disability, Macrotia, Long eyebrows, Motor delay, Muscular hypotonia, Pierre-Robin sequence, Short stature, Strabismus, Symptomatic seizures

Abnormality of the kidney, Abnormality of the mouth, Abnormality of the nose, Autistic behavior, Delayed speech and language development, Epicanthus, Hyperactivity, Increased 30 325610 46XY AGO1 chr1:g.36359345G>A Heterozygous body weight, Intellectual disability, Macrotia, Motor delay, Muscular hypotonia, Sleep disturbance, Stereotypic behavior, Tall stature

Abnormality of the hand, Abnormality of the nose, Autistic behavior, Blindness, Delayed speech and language 31 325598 46XY JARID2 chr6:g.15501447C>T Heterozygous development, Downslanted palpebral fissures, Increased body weight, Intellectual disability, Motor delay, Muscular hypotonia, Stereotypic behavior, Strabismus, Synophrys

Abnormality of the hair, Abnormality of the nose, Aggressive behavior, Autistic behavior, Delayed speech and language development, Hearing impairment, Increased body weight, 32 325602 46XY SIN3B chr19:g.16940261CA>C Heterozygous Intellectual disability, Macrocephaly, Motor delay, Muscular hypotonia, Neonatal hypotonia, Prominent forehead, Stereotypic behavio Abnormality of the hand, Abnormality of the kidney, Abnormality of the philtrum, Abnormality of the skeletal system, Anteverted ears, Autistic behavior, Decreased body weight, Delayed speech 33 325596 46XY FBXO11 chr2:g.48035301CAT>C Heterozygous and language development, Epicanthus, Intrauterine growth retardation, Microcephaly, Motor delay, Stereotypic behavior, Strabismus

Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the philtrum, Abnormality of the skeletal system, 34 325581 46XY MAP3K7 chr6:g.91228271G>A Heterozygous Hypertelorism, Intellectual disability, Intrauterine growth retardation, Micrognathia

Autistic behavior, Delayed speech and language development, 35 325605 46XX HDAC2 chr6:g.114281152C>T Heterozygous Developmental regression, Hyperactivity, Intellectual disability, Muscular hypotonia, Stereotypic behavior, Symptomatic seizures

Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the skeletal system, Decreased body weight, Delayed speech and language development, 36 325591 46XX SMARCC2 chr12:g.56571880G>C Heterozygous Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Microcephaly, Motor delay, Muscular hypotonia, Short stature, Sleep disturbance, Symptomatic seizures, Synophrys

Abnormality of the cardiovascular system, Abnormality of the hand, Abnormality of the kidney, Abnormality of the teeth, Delayed speech and language development, Downslanted 37 325607 46XX CTCFL chr20:g.56098868G>A Heterozygous palpebral fissures, Feeding difficulties, Hearing impairment, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Micrognathia, Motor delay, Muscular hypotonia, Neonatal hypotonia

Abnormality of the mouth, Abnormality of the nose, Autistic 38 325588 46XX HUWE1 chrX:g.53674318G>A Heterozygous behavior, Decreased body weight, Delayed speech and language development, Hypertelorism, Hypertonia, Intellectual disability, Intrauterine growth retardation, Macrotia, Low-set ears, Motor delay, Short stature, Stereotypic behavior, Symptomatic seizures, Upslanted palpebral fissure

Abnormality of the mouth, Abnormality of the philtrum, Abnormality of the teeth, Aggressive behavior, Delayed speech 39 325578 46XY PDE4D chr5:g.58571162A>T Heterozygous and language development, Hyperactivity, Hypermetropia, Hypertelorism, Intellectual disability, Low-set ears, Motor delay, Muscular hypotonia, Stereotypic behavior, Symptomatic seizures

Abnormality of the hair, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the teeth, Autistic behavior, Delayed speech and language development, 40 325579 46XY C22orf39 chr22:g.19434960A>G Heterozygous Epicanthus, Hearing impairment, Hypertrichosis, Hypotelorism, Intellectual disability, Long eyebrows, Low-set ears, Macrocephaly, Motor delay, Symptomatic seizures

Abnormality of the mouth, Abnormality of the skeletal system, Abnormality of the teeth, Aggressive behavior, Anteverted ears, chrX:g.5821346TCGGCGGT Autistic behavior, Feeding difficulties, Hyperactivity, Hypertonia, 41 325571 46XY NLGN4X Hemizygous GGCCA>T Intellectual disability, Low-set ears, Microcephaly, Motor delay, Muscular hypotonia, Posteriorly rotated ears, Retrognathia, Sleep disturbance, Stereotypic behavior, Strabismus

Abnormality of the cardiovascular system, Abnormality of the hand, Abnormality of the male genitalia, Abnormality of the mouth, Abnormality of the philtrum, Autistic behavior, Blindness, Decreased body weight, Delayed speech and language 42 325601 46XY BCOR chrX:g.39911649G>A Hemizygous development, Downslanted palpebral fissures, Epicanthus, Facial asymmetry, Feeding difficulties, Hypertelorism, Intellectual disability, Mandibular prognathia, Microcephaly, Motor delay, Muscular hypotonia, Myopia, Neonatal hypotonia, Nystagmus, Ptosis, Stereotypic behavior, Strabismus

43 325594 46XY SHROOM4 chrX:g.50376558CATG>C Hemizygous Intellectual disability Abnormality of the male genitalia, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the skeletal system, Abnormality of the teeth, Aggressive behavior, Anteverted ears, Decreased body weight, Delayed closure of the anterior fontanelle, Delayed speech and language development, Epicanthus, Hypermetropia, 6 325587 46XY ASCC3 chr6:g.chr6:101215152A>AG Heterozygous Hypertelorism, Hypertrichosis, Intellectual disability, Intrauterine growth retardation, Macrotia, Long eyebrows, Low anterior hairline, Low-set ears, Motor delay, Muscular hypotonia, Neonatal hypotonia, Pierre-Robin sequence, Short palm, Short stature, Sleep disturbance, Tapered finger, Thick vermilion border

Abnormality of the cardiovascular system, Abnormality of the hair, Abnormality of the hand, Abnormality of the mouth, Abnormality of the nose, Abnormality of the palate, Abnormality of the philtrum, Abnormality of the teeth, Delayed speech and 12 325589 46XX CACNA1H chr16:g.1254396C>T Heterozygous language development, Downslanted palpebral fissures, Hypertelorism, Intellectual disability, Low-set ears, Microcephaly, Micrognathia, Motor delay, Short stature, Stereotypic behavior, Symptomatic seizures