Genes associated with “absent speech

453 genes foundHPO: Absent speechOpen Targets: Absent speech1027 ClinVar P/LP variants4 PanelApp panels
How are genes scored? (0–100 composite)
-5–15
ClinGen
0–15
HPO Freq
0–15
Open Targets
0–12
Phen2Gene
0–10
ClinVar
0–8
Constraint
0–8
Dosage
0–8
OMIM CS
0–8
PanelApp
0–5
OMIM
0–5
G2P
0–4
Breadth
Tiers:Strong Candidates (≥20)Consider (≥8)Possible (≥3)
Evidence dots:
HPOClinVarPhen2GeneOpen TargetsPanelApp
hover for details

Strong Candidates

11 genes
1
MECP2

methyl-CpG binding protein 2

32
score
ClinGen: DefinitiveGTR ↑

syndromic X-linked intellectual disability Lubs type

Frequency
88%
n=25
P/LP Variants
5
OT Score
0.34
32
score
ClinGen: DefinitiveP2G #3GTR ↑

Mowat-Wilson syndrome

Frequency
71%
n=96
P/LP Variants
1
OT Score
-
3
ASXL3

ASXL transcriptional regulator 3

30
score
ClinGen: DefinitiveGTR ↑

severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome

Frequency
63%
n=8
P/LP Variants
106
OT Score
0.26
25
score
ClinGen: DefinitiveP2G #1GTR ↑

Angelman syndrome

Frequency
100%
n=27
P/LP Variants
-
OT Score
-
24
score
ClinGen: DefinitiveGTR ↑

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

Frequency
35%
n=34
P/LP Variants
61
OT Score
-
23
score
ClinGen: DefinitiveGTR ↑

neurodevelopmental disorder with language impairment and behavioral abnormalities

Frequency
56%
n=25
P/LP Variants
24
OT Score
-
22
score
ClinGen: DefinitiveP2G #2GTR ↑
Frequency
-
P/LP Variants
1
OT Score
-
21
score
ClinGen: DefinitiveGTR ↑

developmental and epileptic encephalopathy, 54

Frequency
-
P/LP Variants
102
OT Score
-
20
score
ClinGen: DefinitiveGTR ↑

immunodeficiency 49

Frequency
-
P/LP Variants
-
OT Score
-
20DHX30
Def

neurodevelopmental disorder with severe motor impairment and absent language

20SPTBN1
Str

developmental delay, impaired speech, and behavioral abnormalities

Consider

92 genes
19SATB2
Def

neurodevelopmental disorder with behavioral abnormalities, absent speech, and hypotonia

16CASK
Def
15WDR45
Def

neurodegeneration with brain iron accumulation 5

15KDM5A
Lim

neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-pelger-huet anomaly

14UNC80
Def

hypotonia, infantile, with psychomotor retardation and characteristic facies 2

neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter

13EEF1A2
Def

intellectual disability, autosomal dominant 38

13FOXG1
Def

FOXG1 disorder

13CACNA1E
Def

developmental and epileptic encephalopathy, 69

CRANIAL DYSINNERVATION DISORDER, CONGENITAL, WITH ABSENT CORNEAL REFLEX AND DEVELOPMENTAL DELAY; CCDDRD

INTELLECTUAL DEVELOPMENTAL DISORDER WITH SEVERE SPEECH AND AMBULATION DEFECTS; IDDSSAD

NEURODEVELOPMENTAL DISORDER WITH ATAXIC GAIT, ABSENT SPEECH, AND DECREASED CORTICAL WHITE MATTER; NDAGSCW

NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, SEIZURES, AND ABSENT LANGUAGE; NDHSAL

NEURODEVELOPMENTAL DISORDER WITH BEHAVIORAL ABNORMALITIES, ABSENT SPEECH, AND HYPOTONIA; NEDBASH

NEURODEVELOPMENTAL DISORDER WITH FACIAL DYSMORPHISM, ABSENT LANGUAGE, AND PSEUDO-PELGER-HUET ANOMALY; NEDFLPH

NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES, ABSENT SPEECH AND AMBULATION, AND BRAIN ABNORMALITIES; NEDFSAB

NEURODEVELOPMENTAL DISORDER WITH GROWTH IMPAIRMENT, QUADRIPARESIS, AND POOR OR ABSENT SPEECH; NEDGQS

NEURODEVELOPMENTAL DISORDER WITH POOR GROWTH, ABSENT SPEECH, PROGRESSIVE ATAXIA, AND DYSMORPHIC FACIES; NEDGSAF

NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, EPILEPSY, AND ABSENT SPEECH; NEDHES

NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, ABSENT SPEECH, AND HYPOTONIA; NEDMISH

NEURODEVELOPMENTAL DISORDER WITH SEVERE MOTOR IMPAIRMENT, ABSENT LANGUAGE, CEREBRAL HYPOMYELINATION, AND BRAIN ATROPHY; NEDMLHB

NEURODEVELOPMENTAL DISORDER WITH POOR OR ABSENT SPEECH, DYSMORPHIC FACIES, AND BEHAVIORAL ABNORMALITIES; NEDSFB

NEURODEVELOPMENTAL DISORDER WITH ABSENT SPEECH AND MOVEMENT AND BEHAVIORAL ABNORMALITIES; NEDSMB

NEURODEVELOPMENTAL DISORDER WITH SEIZURES AND SPEECH AND WALKING IMPAIRMENT; NEDSSWI

12ZBTB18
Def

intellectual disability, autosomal dominant 22

12COX20
Def
12FLVCR1
Def
12ARID1B
Def

AT-rich interaction domain 1B

12GRIN2B
Def

glutamate ionotropic receptor NMDA type subunit 2B

12MED12
Def

mediator complex subunit 12

12IRF2BPL
Def

neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures

12KAT6A
Def

autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

11ATRX
Def

ATRX chromatin remodeler

11NR4A2
Def
11UNC13A
Lim
11HUWE1
Def

intellectual disability, X-linked syndromic, Turner type

epilepsy, early-onset, 3, with or without developmental delay

11SMC1A
Def

developmental and epileptic encephalopathy, 85, with or without midline brain defects

10MCOLN1
Def#4

mucolipidosis type IV

10FRRS1L
Def

developmental and epileptic encephalopathy, 37

10TMEM231
Def#12

Joubert syndrome 20

10POGZ
Def

pogo transposable element derived with ZNF domain

neurodevelopmental disorder with speech impairment and with or without seizures

10DNM1
Def

developmental and epileptic encephalopathy, 31A

10SPTBN4
Def

neurodevelopmental disorder with hypotonia, neuropathy, and deafness

10KCNB1
Def

neurodevelopmental disorder with seizures and brain abnormalities

10TRIO
Def
10ISCA2
Def

multiple mitochondrial dysfunctions syndrome 4

10IQSEC2
Def
9GNAO1
Def

developmental and epileptic encephalopathy, 17

9MBOAT7
Def

intellectual disability, autosomal recessive 57

9AKT3
Def
9EARS2
Def

leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome

9CNKSR2
Def

intellectual disability, X-linked, syndromic, Houge type

9TBCK
Def

hypotonia, infantile, with psychomotor retardation and characteristic facies 3

9ASH1L
Def

intellectual disability, autosomal dominant 52

9MEF2C
Def

neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

9UBE3B
Def

oculocerebrofacial syndrome, Kaufman type

9AFG2A
Def

microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome

intellectual disability, autosomal recessive 42

9BMPR2
Def
9CHD2
Def
9CUL3
Def
9DDX3X
Def
9DYRK1A
Def
9NIPBL
Def
9PIGV
Mod

hyperphosphatasia with intellectual disability syndrome 1

9SLC6A8
Def
9ARID1A
Def

AT-rich interaction domain 1A

9CTNNB1
Def

catenin beta 1

9TBR1
Def

T-box brain transcription factor 1

developmental and epileptic encephalopathy 106

9KCNQ2
Def

potassium voltage-gated channel subfamily Q member 2

synaptic Ras GTPase activating protein 1

9SETBP1
Def

intellectual disability, autosomal dominant 29

9GPT2
Def

glutamate pyruvate transaminase 2 deficiency

9GABRD
Mod
8SLC1A4
Def

spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome

Possible

313 genes — click to expand

RAB3 GTPase activating protein catalytic subunit 1

8TMEM67
Def

transmembrane protein 67

developmental and epileptic encephalopathy, 39

8GRIA1
Mod

intellectual developmental disorder, autosomal dominant 67

8PRPS1
Def

Arts syndrome

8WDR26
Def

Skraban-Deardorff syndrome

8PIGA
Def

ferro-cerebro-cutaneous syndrome

7KIF1A
Def

intellectual disability, autosomal dominant 9

7COG4
Def

COG4-congenital disorder of glycosylation

7WARS2
Def

neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures

developmental and epileptic encephalopathy, 76

7GABBR2
Mod

developmental and epileptic encephalopathy, 59

7CHAMP1
Def

intellectual disability, autosomal dominant 40

developmental and epileptic encephalopathy, 83

7SIK1
Lim

developmental and epileptic encephalopathy, 30

7PPP3CA
Str

developmental and epileptic encephalopathy 91

7ALS2
Def
7BRD4
Def
7COL3A1
DefSF
7COL5A2
Def
7CPS1
Def
7CTLA4
Def
7GLS
Def
7GRIA4
Mod

neurodevelopmental disorder with or without seizures and gait abnormalities

7H3-3A
Def
7HECW2
Def
7HIBCH
Def
7ICOS
Def
7KDM6B
Def
7MARS2
Def
7NDUFB3
Def
7NDUFS1
Def
7STAT1
Def
7GRIN1
Def

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

7FGF12
Def

developmental and epileptic encephalopathy, 47

7CNNM2
Def

hypomagnesemia, seizures, and intellectual disability 1

Huppke-Brendel syndrome

zinc finger MYND-type containing 11

7NSD1
Def

Sotos syndrome

7MRPS34
Mod

combined oxidative phosphorylation deficiency 32

7RALA
Def

Hiatt-Neu-Cooper neurodevelopmental syndrome

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies

6GTPBP2
Def

Jaberi-Elahi syndrome

multiple mitochondrial dysfunctions syndrome 6

neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities

intellectual disability, X-linked, syndromic, Bain type

progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome

6GCDH
Def

glutaryl-CoA dehydrogenase deficiency

6HNRNPK
Def

Au-Kline syndrome

6CAMK2A
Def

intellectual disability, autosomal dominant 53

6TELO2
Def

TELO2-related intellectual disability-neurodevelopmental disorder

Coffin-Siris syndrome 8

6GRIN2D
Def

developmental and epileptic encephalopathy, 46

6CD28
Mod
6MED27
Str
6TRRAP
Def

developmental delay with or without dysmorphic facies and autism

6STIL
Def

microcephaly 7, primary, autosomal recessive

6CCND2
Def

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

developmental and epileptic encephalopathy 93

6OPHN1
Def

X-linked intellectual disability-cerebellar hypoplasia syndrome

6KCNA2
Def

developmental and epileptic encephalopathy, 32

6RARS2
Def

pontocerebellar hypoplasia type 6

6HTT
Def

Lopes-Maciel-Rodan syndrome

6TIMM50
Def

3-methylglutaconic aciduria type 9

6SCN3A
Def

developmental and epileptic encephalopathy, 62

6C2CD3
Def

orofaciodigital syndrome type 14

developmental and epileptic encephalopathy, 63

PEHO-like syndrome

6MAGEL2
Def

Schaaf-Yang syndrome

microcephaly 15, primary, autosomal recessive

cortical dysplasia-focal epilepsy syndrome

intellectual disability-epilepsy-extrapyramidal syndrome

5VARS1
Def

neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy

developmental and epileptic encephalopathy 102

neurodegeneration, childhood-onset, with cerebellar atrophy

cortical dysplasia, complex, with other brain malformations 9

neurodevelopmental disorder with hypotonia and characteristic brain abnormalities

intellectual disability, autosomal dominant 16

5CASP10
Lim
5DNAH7
Lim
5ERBB4
Lim
5MYL1
Lim
5ZC4H2
Def

Wieacker-Wolff syndrome, female-restricted

5SZT2
Def

developmental and epileptic encephalopathy, 18

intellectual disability, autosomal recessive 64

cerebellar atrophy with seizures and variable developmental delay

5LAS1L
Lim

Wilson-Turner syndrome

intellectual disability, autosomal recessive 58

5PIGP
Mod

developmental and epileptic encephalopathy, 55

5KARS1
Lim

leukoencephalopathy, progressive, infantile-onset, with or without deafness

5EIF3F
Def

intellectual developmental disorder, autosomal recessive 67

5NCAPG2
Lim

Khan-Khan-Katsanis syndrome

5ALG11
Mod

ALG11-congenital disorder of glycosylation

neurodevelopmental disorder with hypotonia and speech delay, with or without seizures

pontocerebellar hypoplasia, type 16

developmental and epileptic encephalopathy, 25

5UBE2A
Def

syndromic X-linked intellectual disability Nascimento type

5LIFR
Def

LIF receptor subunit alpha

5FKRP
Def

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

5FKTN
Def

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

5KCNC2
Def

developmental and epileptic encephalopathy 103

5LARGE1
Def

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

5MMADHC
Def

homocystinuria-megaloblastic anemia cblD type

5NEXMIF
Def

X-linked intellectual disability, Cantagrel type

5NSUN2
Def

intellectual disability, autosomal recessive 5

5POMT2
Def

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

5POT1
Def

cerebroretinal microangiopathy with calcifications and cysts 3

5SOD1
Def

spastic tetraplegia and axial hypotonia, progressive

5SUOX
Def

isolated sulfite oxidase deficiency

5FRMPD4
Def

intellectual disability, X-linked 104

autosomal recessive spinocerebellar ataxia 13

5MFF
Mod

encephalopathy due to defective mitochondrial and peroxisomal fission 2

pontocerebellar hypoplasia, type 14

5PNPT1
Mod

combined oxidative phosphorylation defect type 13

developmental and epileptic encephalopathy, 58

4YME1L1
Lim

optic atrophy 11

4TUBB2A
Def

complex cortical dysplasia with other brain malformations 5

developmental and epileptic encephalopathy 105 with hypopituitarism

4GRIK2
Def

neurodevelopmental disorder with impaired language and ataxia and with or without seizures

4ACADL
Dis
4EXO1
Ref
4PMS1
Ref

BICD cargo adaptor 2

4DOCK7
Def

developmental and epileptic encephalopathy, 23

cerebellar, ocular, craniofacial, and genital syndrome

4ATP1A2
Def

developmental and epileptic encephalopathy 98

lissencephaly 8

Ritscher-Schinzel syndrome 4

neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities

4SPEN
Def

Radio-Tartaglia syndrome

3PCGF2
Str

turnpenny-fry syndrome

spastic paraplegia 86, autosomal recessive

3ALG14
Lim

intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without intellectual disability

3TBCE
Mod

encephalopathy, progressive, with amyotrophy and optic atrophy

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism

congenital hypotonia, epilepsy, developmental delay, and digital anomalies

3BRAT1
Def

neurodevelopmental disorder with cerebellar atrophy and with or without seizures

3SERAC1
Def

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

Data aggregated from HPO/Monarch, ClinVar, OMIM (phenotypes + clinical synopsis), Open Targets, PanelApp, Phen2Gene, and Gene2Phenotype. Click a gene to view full details.