Cleft Palate

Watchlist

(log in to enable)

Retrieved

2021-01-23

Source

Orphanet

Trials

—

Genes

SATB2, IRF6, COL2A1, NEDD4L, MSX1, FOXE1, TBX22, TBX1, TP63, FGFR1, MEIS2, FGFR2, SOX9, COL11A2, FOXC2, KIF7, EDN1, RPL5, HOXA2, RBM10, COL11A1, COL9A3, COL9A2, COL9A1, TMCO1, KCNJ2, ATN1, TSR2, AMER1, SELENOI, EDNRA, FGFR3, FGF9, FGF8, GNAI3, PLCB4, SNRPB, RPL11, PTCH1, TXNL4A, CASK, RPS28, TGDS, RPS26, TGFB3, BMP2, SUMO1, FGF10, TYMS, MTR, TGFB1, RYK, MTHFS, TGFB2, EIF4A3, ARHGAP29, SPRY2, FGF7, FGF2, SLC19A1, SIM2, INTS1, BNC2, MNT, MYC, NMNAT2, NOS3, PDGFRA, MED13L, RARG, BHMT2, PGM1, FGF3, FZD4, ACBD5, DLG1, CHD1, CHUK, CBFB, EGF, CTNND1, GOLGB1, GRHL3, NECTIN1, SOX11, GLI2, SMOC1, TFAP2A, TCOF1, MAFB, KAT6A, CHD7, SMAD3, GAS1, VAX1, RUNX2, RPS19, CILK1, PAX3, PHF8, TWIST1, STAT3, SMC1A, KDM6A, LOXL3, ABCA4, FGD1, TAPT1, PNKP, FILIP1L, ASXL1, RPL35, FGF17, PRDM5, ARID2, MAPRE2, PIGL, PTCH2, CPLX1, SEPTIN9, TUBB, MTMR3, RAI1, STAG2, HYLS1, TBR1, DLL3, EBP, ARID3B, HESX1, IQSEC2, ZFHX4-AS1, SMCHD1, FLRT3, SIX5, PIGN, OFD1, SIK1, HAAO, ITGA8, CEP120, SPECC1L, ESCO2, JMJD1C, RPGRIP1L, VPS13B, BMPER, ARX, EXOC6B, SLC35D1, FSBP, PLXND1, NFASC, STAMBP, STAC3, GDF6, WASHC5, SFI1, KIAA0586, EFTUD2, DOK7, FAM149B1, CYP26C1, HS6ST1, RECQL4, FEZF1, SEMA3E, CEP57, DEPDC5, C2orf91, NTN1, SEC24C, GDF3, GOSR2, POLR1C, TBX4, CHST3, MYMK, KIAA0753, ARNT2, POMT1, TRIP13, COLEC10, DEAF1, FOXH1, SEMA4D, PIGQ, MAD2L2, TMCO4, YAP1, SMC3, BUB3, LARGE1, SEMA3A, NIPBL, SF3B4, CCDC141, CD96, PQBP1, MED12, AMMECR1, RBM8A, LINC01091, RAD54B, CMSS1, POLR1A, HDAC8, CPLANE1, TMEM237, PORCN, XYLT1, SLC25A21, PIEZO2, PROK2, TRPV4, EPG5, SHTN1, FANCM, ZSWIM6, SHROOM3, CC2D2A, TMEM67, WDR35, ARHGAP31, ARID1B, TBC1D24, SALL4, NUP107, RPGRIP1, FAM20C, SCARF2, INPP5E, COLEC11, FTO, FKRP, MEGF10, SLC10A7, BRIP1, MED25, SPRY4, TRIM8, CYRIA, B9D2, CEP290, FRAS1, NAA25, SLX4, COL25A1, TMEM231, ZNF469, KISS1R, HES7, PIGO, DISP1, GREB1L, UBL7, TCTN2, CSPP1, SLC25A22, PALB2, KLHL7, MCTP2, VIRMA, WDR11, PROKR2, CDON, DONSON, PSAT1, POMT2, GMPPB, ANKRD11, UBE2T, CCDC22, DLL1, PGAP2, INTU, RIPPLY2, B9D1, FGF20, CCDC26, B3GAT3, PHGDH, B3GLCT, KIFBP, TMEM107, MESP2, NSMF, C2CD3, SH2B1, B3GALT6, GMNN, WDPCP, OPALIN, TMEM19, FANCI, SETD5, CEP55, RFWD3, FANCL, IMPAD1, MKS1, AHI1, G6PC3, IL17RD, CEP41, POLR1D, GNB1L, CDC45, WNT4, CHST14, RIPK4, FGFRL1, ADA2, SUFU, MBTPS2, TMEM216, PIGP, TCTN3, LINC02476, PTPN11, MYOD1, NPHP1, NOTCH2, NODAL, NID1, NEUROD2, NEK1, NEB, CHRNG, NBN, MYH3, CHRNA1, MUSK, MSX2, KMT2A, MID1, CLK3, MEOX1, COL8A1, COMT, LMX1B, CHRND, NUP88, DPF2, MASP1, RAPSN, RAP1B, RAP1A, RAD51C, RAD51, RAD21, PEX5, PEX2, ERCC4, MAPK1, ORC1, PPP3CA, CENPF, PRRX1, PEX7, CHN1, PDE6D, PAX7, PRKN, OTX2, LFNG, LETM1, CRKL, EFNB1, GJB2, GJA1, GATA3, GATA1, DUSP6, DVL3, FLNB, FLNA, FLII, EIF2S3, KISS1, GPC4, FKTN, FANCG, FANCF, FANCB, FANCE, FANCD2, FANCC, FANCA, GPC3, SLC26A2, GLI3, GNAO1, KCNH1, KCNA1, ANOS1, CTBP1, INPPL1, DCC, IGBP1, DHCR7, HSPG2, DHCR24, DHODH, HOXD13, HNRNPK, NRG1, MKNK2, GP1BB, GNRHR, GNRH1, GNB1, RB1, EYA1, RET, SMARCE1, ARCN1, ARVCF, TBX15, TBX6, TBX2, ATP6V1B2, TACR3, TAC3, STXBP1, CDKL5, STK3, ATR, SOX10, SOX4, SOX3, ATRX, SOX2, SON, BCR, TDGF1, TGFA, ALX3, XRCC2, TRRAP, ARID1A, USP9X, MKKS, ALX1, KMT2D, ACTB, ZIC2, ACTG2, TGFBR1, WNT7A, WNT3, NELFA, NSD2, WHCR, UFD1, HIRA, TGIF1, SMS, SULT2A1, SMARCC2, BUB1B, RPS17, RPS23, RPS24, RPS15A, RPS27, BUB1, RPS10, RPS7, RPL35A, BRCA2, RPL27, RPS29, RREB1, BRCA1, RPL26, RPL15, RPL18, SCN2A, SHH, SIX1, SMARCB1, SIX3, REV3L, SMARCA4, NHLH1, PAX9, COTL1, CSRP3, CALML3, CDH1, CRISPLD2, GABRB3, UVRAG, RPE65, WNT1, CDKN1C, MIR140, AXIN2, LEF1, BMP4, CKAP4, MMP3, OSR2, MTHFR, WNT10A, TTF2, MN1, FOXF2, DLX5, HAND2, IGF2, GREM1, MIR374A, EPHB2, CAT, CBSL, MIR106A, CBS, EPHB3, DLX6, CDKN1B, SLC32A1, RUNX1, STX2, EREG, EPHA4, MIR146A, AHR, CYP1A2, MIR133B, MIR4680, LINC01672, BHMT, ZNF385B, BRWD3, EVC2, AMIGO2, CANT1, TMEM54, AGER, MTHFD1, ETS1, SAG, SPP1, CIB1, SOD1, SNAI1, SIX2, SC5D, FAF1, GTPBP4, KIF3A, MMRN1, PDS5B, ROCK1, RBP4, KAT6B, WDR1, MAP3K7, TBX3, TCF7L2, HDAC4, TGFBR2, TIMP2, NCOR1, TNS1, TP53, NR2C2, ITM2A, WNT9B, NAT2, SHOC2, FGF16, IFT88, RBFOX2, MOK, F10, LRRC32, HTC2, HSPA5, PRMT1, GSTT1, GSTM1, GLI1, GAD1, POU3F4, FGF1, ADAMTS20, CLPTM1L, DDX59, LRMDA, F13A1, ADAMTS9, JAG2, SLC2A9, NXF2, NXF3, JARID2, KIF21A, FBXW7, SMAD2, SMAD7, MEOX2, MYF5, CRNKL1, NT5E, ROR2, FOXP1, PDGFRB, NAT1

Drugs

—

Interested in hearing about new therapies?

A fissure type embryopathy that affects the soft and hard palate to varying degrees.

Epidemiology

The annual incidence varies from 1/3,300 to 1/ 10,000 births. Cleft palate is more frequent in girls.

Clinical description

The cleft is median and connects the buccal cavity to the two nasal fossa and the naso-pharynx. The clinical forms range from a cleft velum (see this term) with a notch in the back of the hard palate to a complete cleft palate that extends to the incisive foramen. Submucous cleft palate is a specific form with muscle and bone dehiscence covered by oral and nasal mucosa. In these cases, diagnosis is more difficult but milk reflux occurs from birth and speech problems can occur. Cleft palate can disrupt sucking-swallowing in newborns to varying degrees. In the non-syndromic forms, normal feeding is possible. In the syndromic forms, there is a risk of food aspiration. Cleft velum disrupts the physiology of the Eustachian tube which can induce incomplete drainage of the middle ear with recurrent otitis and transmission hypoacousia. Dental alignment problems are due to an error in maxillary growth.

Etiology

This embryopathy appears in the 7th to 12th week of pregnancy following an error in fusion of the palatine process. Non-syndromic clefts are believed to be caused by a combination of genetic and environmental factors. Factors such as exposure to teratogenic substances during pregnancy (alcohol, tobacco or drugs) can influence genetic susceptibility.

Diagnostic methods

Diagnosis is clinical.

Differential diagnosis

The presence of associated malformations allows for differentiation between isolated and syndromic forms. Differential diagnoses include hereditary syndromic forms (in 20% of cases), such as Pierre-Robin, Stickler, van der Woude and velocardiofacial syndromes (see these terms).

Antenatal diagnosis

Antenatal diagnosis with an ultrasound is possible from the 2nd trimester onwards by looking for a mandibular retrognathism, an anomaly associated with abnormal amniotic fluid flow. The case is submitted to a multidisciplinary center for prenatal diagnosis in order to establish if it is an isolated anomaly.

Management and treatment

Management requires multidisciplinary medical and surgical intervention from birth until the end of development. It involves primary surgery sometimes followed by secondary surgery (maxillo-facial and plastic). An initial treatment timeline is established during the neonatal period. Secondary management is adapted to the child and based on morphological and functional problems that may arise during growth and development. Speech therapy management involves guidance and rehabilitation from an early age as well as a pharyngoplasty before entering primary school, if necessary. Orthodontic treatment manages dental alignment problems. In the presence of hypomaxilly caused by an error in maxillary growth, intermediate bone and/or orthognatic surgery on the maxillae is necessary. ENT management monitors seromucous (otitis), auditory and phonetic manifestations.

Prognosis

The prognosis depends on the quality of initial management and regular follow-up. Cleft palate can have functional consequences (morphological, phonetic, orthodontic, masticatory and auditory) that require management in a specialized health center. The syndromic forms, in particular a 22q11 deletion, have a poorer prognosis with more serious speech problems requiring complementary surgical treatment.