KEGG   DISEASE: Neurodevelopmental disorder with dysmorphic facies
Entry
H02535                      Disease                                
Name
Neurodevelopmental disorder with dysmorphic facies
  Subgroup
Neurodevelopmental disorder with dysmorphic facies and skeletal anomalies [DS:H02460]
Neurodevelopmental disorder with histone modification defect [DS:H02803]
NED with structural brain anomalies and dysmorphic facies (NEDBAF)
NED with dysmorphic facies and cerebellar hypoplasia (NEDFACH)
NED with cataracts, poor growth, and dysmorphic facies (NDCAGF)
NED with dysmorphic facies and variable seizures (NEDDFAS)
NED with cerebral atrophy and variable facial dysmorphism (NEDCAFD)
Cardiofacioneurodevelopmental syndrome (CFNDS)
Cleft palate, proliferative retinopathy, and developmental delay (CPPRDD)
Hiatt-Neu-Cooper neurodevelopmental syndrome (HINCONS)
Alzahrani-Kuwahara syndrome (ALKUS)
NED with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly (NEDFLPH)
NED with gait disturbance, dysmorphic facies and behavioral abnormalities, X-linked (NEDGFAX)
NED with growth retardation, dysmorphic facies, and corpus callosum abnormalities (NEDGFC)
NED with dysmorphic facies and behavioral abnormalities (NEDFBA)
NED with poor growth, large ears, and dysmorphic facies (NEDGEF)
NED with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies (NEDITPO)
NED with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities (NEDHFDB)
NED with dysmorphic facies, absent speech and ambulation, and brain abnormalities (NEDFSAB)
NED with poor growth, absent speech, progressive ataxia, and dysmorphic facies (NEDGSAF)
NED with hypotonia, poor growth, dysmorphic facies, and agammaglobulinemia (NEDHGFA)
NED with poor or absent speech, dysmorphic facies, and behavioral abnormalities (NEDSFB)
NED with dysmorphic facies, brain anomalies, and seizures (NEDFBS)
  Supergrp
Syndromic neurodevelopmental disorder [DS:H02459]
Description
Neurodevelopmental disorder (NED) with dysmorphic facies is a group of syndromic neurodevelopmental disorders. Some of them have complications in addition to dysmorphic facies. Several underlying genetic causes of these diseases have been identified.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  LD90  Conditions with disorders of intellectual development as a relevant clinical feature
   H02535  Neurodevelopmental disorder with dysmorphic facies
Pathway
hsa04014  Ras signaling pathway
Gene
(NEDBAF) RAC3 [HSA:5881] [KO:K07861]
(NEDFACH) EXOC2 [HSA:55770] [KO:K17637]
(NDCAGF) INTS1 [HSA:26173] [KO:K13138]
(NEDDFAS) EMC10 [HSA:284361] [KO:K23570]
(NEDCAFD) TTC5 [HSA:91875] [KO:K24928]
(CFNDS) CCDC32 [HSA:90416] [KO:K27410]
(CPPRDD) LRRC32 [HSA:2615] [KO:K26316]
(HINCONS) RALA [HSA:5898] [KO:K07834]
(ALKUS) SMG8 [HSA:55181] [KO:K18734]
(NEDFLPH) TMEM147 [HSA:10430] [KO:K26498]
(NEDGFAX) TCEAL1 [HSA:9338] [KO:K26769]
(NEDGFC) FRA10AC1 [HSA:118924] [KO:K13121]
(NEDFBA) SRSF1 [HSA:6426] [KO:K12890]
(NEDGEF) ZNF668 [HSA:79759] [KO:K27106]
(NEDITPO) SMG9 [HSA:56006] [KO:K18735]
(NEDHFDB) WBP4 [HSA:11193] [KO:K13220]
(NEDFSAB) CHASERR [HSA:100507217]
(NEDGSAF/NEDHGFA) SEL1L [HSA:6400] [KO:K14026]
(NEDSFB) NAV3 [HSA:89795] [KO:K23919]
(NEDFBS) GTF3C3 [HSA:9330] [KO:K15201]
Other DBs
ICD-11: LD90.Y
OMIM: 618577 619306 618571 619264 619244 619123 619074 619311 619268 620075 301094 620113 620489 620194 619995 620852 621012 621067 621068 621182 621201
Reference
PMID:30293988 (NEDBAF)
  Authors
Costain G, Callewaert B, Gabriel H, Tan TY, Walker S, Christodoulou J, Lazar T, Menten B, Orkin J, Sadedin S, Snell M, Vanlander A, Vergult S, White SM, Scherer SW, Hayeems RZ, Blaser S, Wodak SJ, Chitayat D, Marshall CR, Meyn MS
  Title
De novo missense variants in RAC3 cause a novel neurodevelopmental syndrome.
  Journal
Genet Med 21:1021-1026 (2019)
DOI:10.1038/s41436-018-0323-y
Reference
PMID:32639540 (NEDFACH)
  Authors
Van Bergen NJ, Ahmed SM, Collins F, Cowley M, Vetro A, Dale RC, Hock DH, de Caestecker C, Menezes M, Massey S, Ho G, Pisano T, Glover S, Gusman J, Stroud DA, Dinger M, Guerrini R, Macara IG, Christodoulou J
  Title
Mutations in the exocyst component EXOC2 cause severe defects in human brain development.
  Journal
J Exp Med 217:e20192040 (2020)
DOI:10.1084/jem.20192040
Reference
PMID:30622326 (NDCAGF)
  Authors
Krall M, Htun S, Schnur RE, Brooks AS, Baker L, de Alba Campomanes A, Lamont RE, Gripp KW, Schneidman-Duhovny D, Innes AM, Mancini GMS, Slavotinek AM
  Title
Biallelic sequence variants in INTS1 in patients with developmental delays, cataracts, and craniofacial anomalies.
  Journal
Eur J Hum Genet 27:582-593 (2019)
DOI:10.1038/s41431-018-0298-9
Reference
PMID:33531666 (NEDDFAS)
  Authors
Shao DD, Straussberg R, Ahmed H, Khan A, Tian S, Hill RS, Smith RS, Majmundar AJ, Ameziane N, Neil JE, Yang E, Al Tenaiji A, Jamuar SS, Schlaeger TM, Al-Saffar M, Hovel I, Al-Shamsi A, Basel-Salmon L, Amir AZ, Rento LM, Lim JY, Ganesan I, Shril S, Evrony G, Barkovich AJ, Bauer P, Hildebrandt F, Dong M, Borck G, Beetz C, Al-Gazali L, Eyaid W, Walsh CA
  Title
A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features.
  Journal
Genet Med 23:1158-1162 (2021)
DOI:10.1038/s41436-021-01097-x
Reference
PMID:32439809 (NEDCAFD)
  Authors
Rasheed A, Gumus E, Zaki M, Johnson K, Manzoor H, LaForce G, Ross D, McEvoy-Venneri J, Stanley V, Lee S, Virani A, Ben-Omran T, Gleeson JG, Naz S, Schaffer A
  Title
Bi-allelic TTC5 variants cause delayed developmental milestones and intellectual disability.
  Journal
J Med Genet 58:237-246 (2021)
DOI:10.1136/jmedgenet-2020-106849
Reference
PMID:32822602 (NEDFASB)
  Authors
Humbert J, Salian S, Makrythanasis P, Lemire G, Rousseau J, Ehresmann S, Garcia T, Alasiri R, Bottani A, Hanquinet S, Beaver E, Heeley J, Smith ACM, Berger SI, Antonarakis SE, Yang XJ, Cote J, Campeau PM
  Title
De Novo KAT5 Variants Cause a Syndrome with Recognizable Facial Dysmorphisms, Cerebellar Atrophy, Sleep Disturbance, and Epilepsy.
  Journal
Am J Hum Genet 107:564-574 (2020)
DOI:10.1016/j.ajhg.2020.08.002
Reference
PMID:32307552 (CFNDS)
  Authors
Harel T, Griffin JN, Arbogast T, Monroe TO, Palombo F, Martinelli M, Seri M, Pippucci T, Elpeleg O, Katsanis N
  Title
Loss of function mutations in CCDC32 cause a congenital syndrome characterized by craniofacial, cardiac and neurodevelopmental anomalies.
  Journal
Hum Mol Genet 29:1489-1497 (2020)
DOI:10.1093/hmg/ddaa073
Reference
PMID:30976112 (CPPRDD)
  Authors
Harel T, Levy-Lahad E, Daana M, Mechoulam H, Horowitz-Cederboim S, Gur M, Meiner V, Elpeleg O
  Title
Homozygous stop-gain variant in LRRC32, encoding a TGFbeta receptor, associated with cleft palate, proliferative retinopathy, and developmental delay.
  Journal
Eur J Hum Genet 27:1315-1319 (2019)
DOI:10.1038/s41431-019-0380-y
Reference
PMID:30500825 (HINCONS)
  Authors
Hiatt SM, Neu MB, Ramaker RC, Hardigan AA, Prokop JW, Hancarova M, Prchalova D, Havlovicova M, Prchal J, Stranecky V, Yim DKC, Powis Z, Keren B, Nava C, Mignot C, Rio M, Revah-Politi A, Hemati P, Stong N, Iglesias AD, Suchy SF, Willaert R, Wentzensen IM, Wheeler PG, Brick L, Kozenko M, Hurst ACE, Wheless JW, Lacassie Y, Myers RM, Barsh GS, Sedlacek Z, Cooper GM
  Title
De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small GTPase, cause intellectual disability and developmental delay.
  Journal
PLoS Genet 14:e1007671 (2018)
DOI:10.1371/journal.pgen.1007671
Reference
PMID:33242396 (ALKUS)
  Authors
Alzahrani F, Kuwahara H, Long Y, Al-Owain M, Tohary M, AlSayed M, Mahnashi M, Fathi L, Alnemer M, Al-Hamed MH, Lemire G, Boycott KM, Hashem M, Han W, Al-Maawali A, Al Mahrizi F, Al-Thihli K, Gao X, Alkuraya FS
  Title
Recessive, Deleterious Variants in SMG8 Expand the Role of Nonsense-Mediated Decay in Developmental Disorders in Humans.
  Journal
Am J Hum Genet 107:1178-1185 (2020)
DOI:10.1016/j.ajhg.2020.11.007
Reference
PMID:36044892 (NEDFLPH)
  Authors
Thomas Q, Motta M, Gautier T, Zaki MS, Ciolfi A, Paccaud J, Girodon F, Boespflug-Tanguy O, Besnard T, Kerkhof J, McConkey H, Masson A, Denomme-Pichon AS, Cogne B, Trochu E, Vignard V, El It F, Rodan LH, Alkhateeb MA, Jamra RA, Duplomb L, Tisserant E, Duffourd Y, Bruel AL, Jackson A, Banka S, McEntagart M, Saggar A, Gleeson JG, Sievert D, Bae H, Lee BH, Kwon K, Seo GH, Lee H, Saeed A, Anjum N, Cheema H, Alawbathani S, Khan I, Pinto-Basto J, Teoh J, Wong J, Sahari UBM, Houlden H, Zhelcheska K, Pannetier M, Awad MA, Lesieur-Sebellin M, Barcia G, Amiel J, Delanne J, Philippe C, Faivre L, Odent S, Bertoli-Avella A, Thauvin C, Sadikovic B, Reversade B, Maroofian R, Govin J, Tartaglia M, Vitobello A
  Title
Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huet anomaly.
  Journal
Am J Hum Genet 109:1909-1922 (2022)
DOI:10.1016/j.ajhg.2022.08.008
Reference
PMID:36368327 (NEDGFAX)
  Authors
Hijazi H, Reis LM, Pehlivan D, Bernstein JA, Muriello M, Syverson E, Bonner D, Estiar MA, Gan-Or Z, Rouleau GA, Lyulcheva E, Greenhalgh L, Tessarech M, Colin E, Guichet A, Bonneau D, van Jaarsveld RH, Lachmeijer AMA, Ruaud L, Levy J, Tabet AC, Ploski R, Rydzanicz M, Kepczynski L, Polatynska K, Li Y, Fatih JM, Marafi D, Rosenfeld JA, Coban-Akdemir Z, Bi W, Gibbs RA, Hobson GM, Hunter JV, Carvalho CMB, Posey JE, Semina EV, Lupski JR
  Title
TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions.
  Journal
Am J Hum Genet 109:2270-2282 (2022)
DOI:10.1016/j.ajhg.2022.10.007
Reference
PMID:35821753 (NEDGFC)
  Authors
Alsaleh N, Alhashem A, Tabarki B, Mohamed S, Alharby E, Alkuraya FS, Almontashiri NAM
  Title
A Biallelic Variant in FRA10AC1 Is Associated With Neurodevelopmental Disorder and Growth Retardation.
  Journal
Neurol Genet 8:e200010 (2022)
DOI:10.1212/NXG.0000000000200010
Reference
PMID:37071997 (NEDFBA)
  Authors
Bogaert E, Garde A, Gautier T, Rooney K, Duffourd Y, LeBlanc P, van Reempts E, Tran Mau-Them F, Wentzensen IM, Au KS, Richardson K, Northrup H, Gatinois V, Genevieve D, Louie RJ, Lyons MJ, Laulund LW, Brasch-Andersen C, Maxel Juul T, El It F, Marle N, Callier P, Relator R, Haghshenas S, McConkey H, Kerkhof J, Cesario C, Novelli A, Brunetti-Pierri N, Pinelli M, Pennamen P, Naudion S, Legendre M, Courdier C, Trimouille A, Fenzy MD, Pais L, Yeung A, Nugent K, Roeder ER, Mitani T, Posey JE, Calame D, Yonath H, Rosenfeld JA, Musante L, Faletra F, Montanari F, Sartor G, Vancini A, Seri M, Besmond C, Poirier K, Hubert L, Hemelsoet D, Munnich A, Lupski JR, Philippe C, Thauvin-Robinet C, Faivre L, Sadikovic B, Govin J, Dermaut B, Vitobello A
  Title
SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability.
  Journal
Am J Hum Genet 110:790-808 (2023)
DOI:10.1016/j.ajhg.2023.03.016
Reference
PMID:34313816 (NEDGEF)
  Authors
Alsaif HS, Al Ali H, Faqeih E, Ramadan SM, Barth M, Colin E, Prouteau C, Bonneau D, Ziegler A, Alkuraya FS
  Title
ZNF668 deficiency causes a recognizable disorder of DNA damage repair.
  Journal
Hum Genet 140:1395-1401 (2021)
DOI:10.1007/s00439-021-02321-z
Reference
PMID:35087184 (NEDITPO)
  Authors
Rahikkala E, Urpa L, Ghimire B, Topa H, Kurki MI, Koskela M, Airavaara M, Hamalainen E, Pylkas K, Korkko J, Savolainen H, Suoranta A, Bertoli-Avella A, Rolfs A, Mattila P, Daly M, Palotie A, Pietilainen O, Moilanen J, Kuismin O
  Title
A novel variant in SMG9 causes intellectual disability, confirming a role for nonsense-mediated decay components in neurocognitive development.
  Journal
Eur J Hum Genet 30:619-627 (2022)
DOI:10.1038/s41431-022-01046-5
Reference
PMID:37963460 (NEDHFDB)
  Authors
Engal E, Oja KT, Maroofian R, Geminder O, Le TL, Marzin P, Guimier A, Mor E, Zvi N, Elefant N, Zaki MS, Gleeson JG, Muru K, Pajusalu S, Wojcik MH, Pachat D, Elmaksoud MA, Chan Jeong W, Lee H, Bauer P, Zifarelli G, Houlden H, Daana M, Elpeleg O, Amiel J, Lyonnet S, Gordon CT, Harel T, Ounap K, Salton M, Mor-Shaked H
  Title
Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.
  Journal
Am J Hum Genet 110:2112-2119 (2023)
DOI:10.1016/j.ajhg.2023.10.013
Reference
PMID:38821540 (NEDHAFA)
  Authors
Greene D, Thys C, Berry IR, Jarvis J, Ortibus E, Mumford AD, Freson K, Turro E
  Title
Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders.
  Journal
Nat Med 10.1038/s41591-024-03085-5 (2024)
DOI:10.1038/s41591-024-03085-5
Reference
PMID:39442041 (NEDFSAB)
  Authors
Ganesh VS, Riquin K, Chatron N, Yoon E, Lamar KM, Aziz MC, Monin P, O'Leary MC, Goodrich JK, Garimella KV, England E, Weisburd B, Aguet F, Bacino CA, Murdock DR, Dai H, Rosenfeld JA, Emrick LT, Ketkar S, Sarusi Y, Sanlaville D, Kayani S, Broadbent B, Pengam A, Isidor B, Bezieau S, Cogne B, MacArthur DG, Ulitsky I, Carvill GL, O'Donnell-Luria A
  Title
Neurodevelopmental Disorder Caused by Deletion of CHASERR, a lncRNA Gene.
  Journal
N Engl J Med 391:1511-1518 (2024)
DOI:10.1056/NEJMoa2400718
Reference
PMID:37943610 (NEDGSAF)
  Authors
Wang HH, Lin LL, Li ZJ, Wei X, Askander O, Cappuccio G, Hashem MO, Hubert L, Munnich A, Alqahtani M, Pang Q, Burmeister M, Lu Y, Poirier K, Besmond C, Sun S, Brunetti-Pierri N, Alkuraya FS, Qi L
  Title
Hypomorphic variants of SEL1L-HRD1 ER-associated degradation are associated with neurodevelopmental disorders.
  Journal
J Clin Invest 134:170054 (2024)
DOI:10.1172/JCI170054
Reference
PMID:37943617 (NEDHGFA)
  Authors
Weis D, Lin LL, Wang HH, Li ZJ, Kusikova K, Ciznar P, Wolf HM, Leiss-Piller A, Wang Z, Wei X, Weis S, Skalicka K, Hrckova G, Danisovic L, Soltysova A, Yang TT, Feichtinger RG, Mayr JA, Qi L
  Title
Biallelic Cys141Tyr variant of SEL1L is associated with neurodevelopmental disorders, agammaglobulinemia, and premature death.
  Journal
J Clin Invest 134:170882 (2024)
DOI:10.1172/JCI170882
Reference
PMID:38977784 (NEDSFB)
  Authors
Ghaffar A, Akhter T, Stromme P, Misceo D, Khan A, Frengen E, Umair M, Isidor B, Cogne B, Khan AA, Bruel AL, Sorlin A, Kuentz P, Chiaverini C, Innes AM, Zech M, Balaz M, Havrankova P, Jech R, Ahmed ZM, Riazuddin S, Riazuddin S
  Title
Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly.
  Journal
Commun Biol 7:831 (2024)
DOI:10.1038/s42003-024-06466-1
Reference
PMID:39636576 (NEDFBS)
  Authors
De Hayr L, Blok LER, Dias KR, Long J, Begemann A, Moir RD, Willis IM, Mocera M, Siegel G, Steindl K, Evans CA, Zhu Y, Zhang F, Field M, Ma A, Ades L, Josephi-Taylor S, Pfundt R, Zaki MS, Tomoum H, Gregor A, Laube J, Reis A, Maddirevula S, Hashem MO, Zweier M, Alkuraya FS, Maroofian R, Buckley MF, Gleeson JG, Zweier C, Coll-Tane M, Koolen DA, Rauch A, Roscioli T, Schenck A, Harvey RJ
  Title
Biallelic variants in GTF3C3 result in an autosomal recessive disorder with intellectual disability.
  Journal
Genet Med 27:101253 (2025)
DOI:10.1016/j.gim.2024.101253
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