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Speech apraxia v1.36 SET Zornitza Stark Marked gene: SET as ready
Speech apraxia v1.36 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Speech apraxia v1.36 SET Zornitza Stark Classified gene: SET as Green List (high evidence)
Speech apraxia v1.36 SET Zornitza Stark Gene: set has been classified as Green List (High Evidence).
Speech apraxia v1.34 SETD5 Zornitza Stark Marked gene: SETD5 as ready
Speech apraxia v1.34 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Speech apraxia v1.34 SETD5 Zornitza Stark Classified gene: SETD5 as Green List (high evidence)
Speech apraxia v1.34 SETD5 Zornitza Stark Gene: setd5 has been classified as Green List (High Evidence).
Speech apraxia v1.31 SMARCA2 Hali Van Niel gene: SMARCA2 was added
gene: SMARCA2 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA2 were set to 41530369; 39931922; 32694869
Phenotypes for gene: SMARCA2 were set to Nicolaides-Baraitser syndrome (MIM#601358); Blepharophimosis-impaired intellectual development syndrome (MIM#619293)
Review for gene: SMARCA2 was set to GREEN
Added comment: Two reported individual with CAS and de novo missense variants (c.2870 A > G; p.(Gln957Arg); c.3484 C > T; p.(Arg1162Cys)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic findings from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with CAS and SMARCA2 variant (Supp Table 6).

Phenotype dependent on variant position along gene (PMID: 32694869). Both phenotypes implicated with CAS.
Sources: Expert List, Literature
Speech apraxia v1.31 SLC6A1 Hali Van Niel gene: SLC6A1 was added
gene: SLC6A1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SLC6A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC6A1 were set to 41530369; 39931922
Phenotypes for gene: SLC6A1 were set to Myoclonic-atonic epilepsy (MIM#616421
Review for gene: SLC6A1 was set to GREEN
Added comment: Reported individual with CAS and de novo missense variant (c.1097_1098delinsCT; p.(Leu366Pro)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline.

Mitchel et al. (2025; PMID: 39931922) report two individuals with dysarthria and SLC6A1 variant (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 SETD5 Hali Van Niel gene: SETD5 was added
gene: SETD5 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD5 were set to 41530369; 39931922
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, 23 (MIM#615761)
Review for gene: SETD5 was set to GREEN
Added comment: Reported individual with CAS and de novo splicing variant (c.2347-7 A > G) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report five individuals SETD5 variants (4 with CAS, 1 with dysarthria).

Unspecified speech delay/impairment reported commonly in individuals with SETD5 variants (PMID: 29484850)
Sources: Expert List, Literature
Speech apraxia v1.31 SET Hali Van Niel gene: SET was added
gene: SET was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SET were set to 41530369; 39931922
Phenotypes for gene: SET were set to Intellectual developmental disorder, 58 (MIM#618106).
Review for gene: SET was set to GREEN
Added comment: Reported individual with CAS and de novo nonsense variant (c.103_104del; p.(Ile35*)) (Van Niel et al., 2026; PMID: 41530369), Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with CAS and SET variant (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 PPP2R5D Hali Van Niel gene: PPP2R5D was added
gene: PPP2R5D was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R5D were set to 41530369; 39931922; 32074998
Phenotypes for gene: PPP2R5D were set to Intellectual developmental disorder 35 (MIM#616355)
Review for gene: PPP2R5D was set to GREEN
Added comment: Individual with CAS reported with de novo nonsense variant, c.751 G > T; p.(Asp251Tyr) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report one individual with PPP2R5D variant with CAS (Supp Table 6).

Almost all individuals with a PPP2R5D variant have speech impairment, hallmark of disorder (PMID: 32074998)
Sources: Expert List, Literature
Speech apraxia v1.31 SCN8A Hali Van Niel gene: SCN8A was added
gene: SCN8A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN8A were set to 41530369; 39931922
Phenotypes for gene: SCN8A were set to Cognitive impairment with or without cerebellar ataxia (MIM#614306)
Review for gene: SCN8A was set to GREEN
Added comment: One reported individual with CAS and de novo missense variant, c.417 G > A; p.(Met139Ile) (Van Niel et al., 2026; PMID: 41530369). Validated diagnostic finding from VCGS clinical NATA pipeline

Mitchel et al. (2025; PMID: 39931922) report two individuals with CAS and SCN8A variants (Supp Table 6).
Sources: Expert List, Literature
Speech apraxia v1.31 KDM5C Hali Van Niel reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 41530369, 39931922; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM#300534); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Speech apraxia v1.31 FOXP1 Hali Van Niel gene: FOXP1 was added
gene: FOXP1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to (PMID: 41530369; 34109629; 39931922)
Phenotypes for gene: FOXP1 were set to intellectual disability-severe speech delay-mild dysmorphism syndrome (MONDO: 0013352)
Review for gene: FOXP1 was set to GREEN
Added comment: Individual with CAS reported with de novo nonsense variant, c.1426 C > T; p.(Gln476*) (Van Niel et al., 2026; PMID: 41530369)

Speech impairment hallmark in disorder. Braden et al. (2021; PMID: 34109629) report 16 individuals with FOXP1 variants assessed by speech pathologist, 16/16 with dysarthric features and 14/16 with speech apraxia features.

Mitchel et al. (2025; PMID: 39931922) report three individuals with FOXP1 variants (1 with CAS, 2 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.31 KDM5C Hali Van Niel reviewed gene: KDM5C: Rating: AMBER; Mode of pathogenicity: None; Publications: (PMID: 41530369, 39931922); Phenotypes: intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM#300534); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Speech apraxia v1.31 GNAI1 Hali Van Niel gene: GNAI1 was added
gene: GNAI1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: GNAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAI1 were set to PMID: 41530369; 39931922; 33473207
Phenotypes for gene: GNAI1 were set to neurodevelopmental disorder with hypotonia, impaired speech, and behavioural abnormalities (MIM#619854)
Review for gene: GNAI1 was set to AMBER
Added comment: One reported individual with CAS and de novo missense variant (c.518 A > T; p.(Asp173Val)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report one individual with dysarthria and GNAI1 variant (Supp Table 6).

Disorder characterised by impaired speech. Phenotype has variable expressivity ranging from mild to severe (PMID: 33473207)
Sources: Expert List, Literature
Speech apraxia v1.29 EHMT1 Hali Van Niel gene: EHMT1 was added
gene: EHMT1 was added to Speech apraxia. Sources: Expert List
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHMT1 were set to PMID: 41530369; PMID: 38290825
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1 (MIM#610253)
Review for gene: EHMT1 was set to GREEN
Added comment: Two reported individuals with CAS and EHMT1 variants (c.3229 C > T; p.(Gln1077*); c.2842 C > T; p.(Arg948Trp)) (Van Niel et al., 2026; PMID: 41530369)

Morrison et al. (2024; PMID: 38290825) reported 49 individuals with EHMT1 variants assessed by a speech pathologist, 34/49 with dysarthria and 29/49 with CAS.
Sources: Expert List
Speech apraxia v1.29 CAMTA1 Hali Van Niel gene: CAMTA1 was added
gene: CAMTA1 was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to PMID: 41530369; PMID: 39931922; PMID: 33131045
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioural abnormalities (MIM#614756)
Review for gene: CAMTA1 was set to GREEN
Added comment: One reported individual with CAS and dysarthria with a denovo frameshift variant (c.2072_2075del; p.(Thr691Argfs*35)) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 3 individuals with CAMTA1 variants with dysarthria

Jacobs et al. (2020; PMID: 33131045) report 9 individuals with CAMTA1 variants, 5/9 with dysarthria and 9/9 with unspecified speech delay
Sources: Expert List, Literature
Speech apraxia v1.28 CACNA1A Hali Van Niel gene: CACNA1A was added
gene: CACNA1A was added to Speech apraxia. Sources: Expert List,Literature
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to (PMID: 41530369); (PMID: 39931922)
Phenotypes for gene: CACNA1A were set to CACNA1A-related complex neurodevelopmental disorder (MONDO:0100254)
Review for gene: CACNA1A was set to GREEN
Added comment: Three reported individuals with CAS in LoF nonsense variants (c.3829 C > T; p.(Arg1277*), paternal); c.492 C > G; p.(Tyr164*), maternal; c.592 C > T; p.(Arg198*), maternal) (Van Niel et al., 2026; PMID: 41530369)

Mitchel et al. (2025; PMID: 39931922) report 11 individuals with CACNA1A variants (4 with CAS and 8 with dysarthria)
Sources: Expert List, Literature
Speech apraxia v1.21 Zornitza Stark removed gene:SETD5 from the panel
Speech apraxia v1.20 Zornitza Stark removed gene:SETD2 from the panel
Speech apraxia v1.19 Zornitza Stark removed gene:SET from the panel
Speech apraxia v1.6 SET Thomas Scerri Deleted their review
Speech apraxia v1.6 FOXP1 Thomas Scerri gene: FOXP1 was added
gene: FOXP1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP1 were set to 34109629
Phenotypes for gene: FOXP1 were set to Intellectual developmental disorder with language impairment with or without autistic features, MIM# 613670
Review for gene: FOXP1 was set to GREEN
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant. The proband shows mild CAS.

Another in-house (unpublished) CAS proband with a de novo splice variant that is listed as pathogenic in ClinVar.

Braden et al., (2021; 34109629) examined 29 probands with pathogenic FOXP1 variants, and reported that "All verbal patients had dysarthric and apraxic features, with phonologicaldeficits in most (14 out of 16)."
Sources: Expert list, Expert Review
Speech apraxia v1.6 TRIM8 Thomas Scerri gene: TRIM8 was added
gene: TRIM8 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TRIM8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TRIM8 were set to Focal segmental glomerulosclerosis and neurodevelopmental syndrome, MIM# 619428
Review for gene: TRIM8 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 TAB2 Thomas Scerri gene: TAB2 was added
gene: TAB2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: TAB2 were set to Congenital heart defects, nonsyndromic, 2, MIM# 614980
Review for gene: TAB2 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SPTBN1 Thomas Scerri gene: SPTBN1 was added
gene: SPTBN1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SPTBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SPTBN1 were set to Developmental delay, impaired speech, and behavioral abnormalities, MIM# 619475
Review for gene: SPTBN1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SMARCA2 Thomas Scerri gene: SMARCA2 was added
gene: SMARCA2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCA2 were set to Blepharophimosis-impaired intellectual development syndrome, MIM# 619293; Nicolaides-Baraitser syndrome, MIM# 601358
Review for gene: SMARCA2 was set to RED
Added comment: Two in-house (as yet unpublished) CAS probands with pathogenic variants.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SLC6A1 Thomas Scerri gene: SLC6A1 was added
gene: SLC6A1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SLC6A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SLC6A1 were set to Myoclonic-atonic epilepsy, MIM# 616421
Review for gene: SLC6A1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SETD5 Thomas Scerri gene: SETD5 was added
gene: SETD5 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SETD5 were set to Intellectual developmental disorder, autosomal dominant 23, MIM# 615761
Review for gene: SETD5 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SETD2 Thomas Scerri gene: SETD2 was added
gene: SETD2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SETD2 were set to Intellectual developmental disorder, autosomal dominant 70, MIM# 620157; Luscan-Lumish syndrome, MIM# 616831; Rabin-Pappas syndrome, MIM# 620155
Review for gene: SETD2 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SET Thomas Scerri gene: SET was added
gene: SET was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SET were set to Intellectual developmental disorder, autosomal dominant 58, MIM# 618106
Review for gene: SET was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 SCN8A Thomas Scerri gene: SCN8A was added
gene: SCN8A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SCN8A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SCN8A were set to Cognitive impairment with or without cerebellar ataxia, MIM# 614306; Developmental and epileptic encephalopathy 13, MIM# 614558; Seizures, benign familial infantile, 5, MIM# 617080
Review for gene: SCN8A was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 RAF1 Thomas Scerri gene: RAF1 was added
gene: RAF1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: RAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: RAF1 were set to Cardiomyopathy, dilated, 1NN, MIM# 615916; LEOPARD syndrome 2, MIM# 611554; Noonan syndrome 5, MIM# 611553
Review for gene: RAF1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 PPP2R5D Thomas Scerri gene: PPP2R5D was added
gene: PPP2R5D was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PPP2R5D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PPP2R5D were set to Houge-Janssens syndrome 1, MIM# 616355
Review for gene: PPP2R5D was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 NSD1 Thomas Scerri gene: NSD1 was added
gene: NSD1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NSD1 were set to Sotos syndrome, MIM# 117550
Review for gene: NSD1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 KCND3 Thomas Scerri gene: KCND3 was added
gene: KCND3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: KCND3 were set to Brugada syndrome 9, MIM# 616399; Spinocerebellar ataxia 19, MIM# 607346
Review for gene: KCND3 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 GNAI1 Thomas Scerri gene: GNAI1 was added
gene: GNAI1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNAI1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GNAI1 were set to Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities, MIM# 619854
Review for gene: GNAI1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 FBXW7 Thomas Scerri gene: FBXW7 was added
gene: FBXW7 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FBXW7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FBXW7 were set to Developmental delay, hypotonia, and impaired language, MIM# 620012
Review for gene: FBXW7 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 EHMT1 Thomas Scerri gene: EHMT1 was added
gene: EHMT1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome 1, MIM# 610253
Review for gene: EHMT1 was set to RED
Added comment: Two in-house (as yet unpublished) CAS probands with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 CAMTA1 Thomas Scerri gene: CAMTA1 was added
gene: CAMTA1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CAMTA1 were set to Cerebellar dysfunction with variable cognitive and behavioral abnormalities, MIM# 614756
Review for gene: CAMTA1 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 CAMK2A Thomas Scerri gene: CAMK2A was added
gene: CAMK2A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CAMK2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CAMK2A were set to Intellectual developmental disorder, autosomal dominant 53, MIM# 617798
Review for gene: CAMK2A was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert list, Expert Review
Speech apraxia v1.6 CACNA1A Thomas Scerri gene: CACNA1A was added
gene: CACNA1A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to 38712155
Phenotypes for gene: CACNA1A were set to Developmental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Migraine, familial hemiplegic, 1, MIM# 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, MIM# 141500; Spinocerebellar ataxia 6, MIM# 183086
Review for gene: CACNA1A was set to GREEN
Added comment: Three in-house (as yet unpublished) CAS probands with pathogenic variants.

Magielski et al. (2024; PMID: 38712155) report 1 individual with speech apraxia and a CACNA1C genetic diagnosis.
Sources: Expert list, Expert Review
Speech apraxia v1.3 BPTF Thomas Scerri gene: BPTF was added
gene: BPTF was added to Speech apraxia. Sources: Expert Review,Expert list
Mode of inheritance for gene: BPTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BPTF were set to Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM# 617755
Review for gene: BPTF was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert Review, Expert list
Speech apraxia v1.3 ANK2 Thomas Scerri gene: ANK2 was added
gene: ANK2 was added to Speech apraxia. Sources: Expert Review
Mode of inheritance for gene: ANK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANK2 were set to 37195288
Phenotypes for gene: ANK2 were set to Cardiac arrhythmia, ankyrin-B-relatedNeurodevelopmental disorder (MONDO:0700092), gene-related
Review for gene: ANK2 was set to RED
Added comment: An in-house (as yet unpublished) CAS proband with a pathogenic variant.
Sources: Expert Review
Speech apraxia v1.3 SETBP1 Thomas Scerri commented on gene: SETBP1: Two in-house (as yet unpublished) CAS probands with pathogenic variants.
Speech apraxia v1.1 SETD1A Zornitza Stark Classified gene: SETD1A as Green List (high evidence)
Speech apraxia v1.1 SETD1A Zornitza Stark Gene: setd1a has been classified as Green List (High Evidence).
Speech apraxia v1.0 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: GREEN; Changed publications: 29463886, 32346159, 36117209
Speech apraxia v1.0 SETD1A Thomas Scerri changed review comment from: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Kaspi et al. (2022; PMID: 36117209) report a CAS proband with a de novo SETD1A splice acceptor variant.

An independent (unpublished) in-house CAS proband has a de novo SETD1A frameshift variant.

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Speech apraxia v0.38 SETD1A Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1A frameshift variant (Eising et al., 2019; PMID: 29463886)

Fifteen further independent probands with loss-of-function SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Speech apraxia v0.38 SETD1B Thomas Scerri changed review comment from: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review; to: First reported CAS case with a de novo SETD1B missense variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.38 SETBP1 Thomas Scerri changed review comment from: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.".
Sources: Expert list, Expert Review; to: First reported CAS case with a SETBP1 frameshift variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with loss-of-function SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%; 25/31) being the most common diagnosis.".
Sources: Expert list, Expert Review
Speech apraxia v0.33 SETD1B Zornitza Stark Marked gene: SETD1B as ready
Speech apraxia v0.33 SETD1B Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence).
Speech apraxia v0.33 SETD1B Zornitza Stark Classified gene: SETD1B as Red List (low evidence)
Speech apraxia v0.33 SETD1B Zornitza Stark Gene: setd1b has been classified as Red List (Low Evidence).
Speech apraxia v0.31 ZBTB18 Thomas Scerri gene: ZBTB18 was added
gene: ZBTB18 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB18 were set to 36117209
Phenotypes for gene: ZBTB18 were set to Intellectual developmental disorder, autosomal dominant 22, MIM# 612337
Review for gene: ZBTB18 was set to RED
Added comment: First reported CAS case with an de novo nonsense ZBTB18 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 TRIP12 Thomas Scerri gene: TRIP12 was added
gene: TRIP12 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIP12 were set to 36117209
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM# 617752
Review for gene: TRIP12 was set to RED
Added comment: First reported CAS case with a de novo exon duplication of TRIP12 (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 TAOK2 Thomas Scerri gene: TAOK2 was added
gene: TAOK2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TAOK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK2 were set to 36117209
Phenotypes for gene: TAOK2 were set to Neurodevelopmental disorder (MONDO:0700092), TAOK2-related
Review for gene: TAOK2 was set to RED
Added comment: First reported CAS case with an de novo missense TAOK2 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 SPAST Thomas Scerri gene: SPAST was added
gene: SPAST was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPAST were set to 36117209
Phenotypes for gene: SPAST were set to Spastic paraplegia 4, autosomal dominant, MIM# 182601
Review for gene: SPAST was set to RED
Added comment: First reported CAS case with an de novo missense SPAST variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 SHANK3 Thomas Scerri gene: SHANK3 was added
gene: SHANK3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 36117209; 33293697
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome, MIM# 606232
Review for gene: SHANK3 was set to GREEN
Added comment: First reported CAS case with an de novo frameshift SHANK3 variant (Kaspi et al., 2022; PMID: 36117209).

Brignell et al. (2021; PMID: 33293697) report 2 cases of CAS in a cohort of individuals with Phelan-McDermid/22q13 deletion syndrome, caused by heterozygous loss of function of SHANK3.
Sources: Expert list, Expert Review
Speech apraxia v0.31 SETD1B Thomas Scerri gene: SETD1B was added
gene: SETD1B was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1B were set to 36117209
Phenotypes for gene: SETD1B were set to Intellectual developmental disorder with seizures and language delay, MIM# 619000
Review for gene: SETD1B was set to RED
Added comment: First reported CAS case with a de novo missense SETD1B variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.31 RBFOX3 Thomas Scerri gene: RBFOX3 was added
gene: RBFOX3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: RBFOX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RBFOX3 were set to 36117209; 24039908
Phenotypes for gene: RBFOX3 were set to Neurodevelopmental disorder (MONDO:0700092), RBFOX3-related
Review for gene: RBFOX3 was set to AMBER
Added comment: First reported CAS case with a paternally inherited nonsense RBFOX3 variant (Kaspi et al., 2022; PMID: 36117209). The carrier father was also affected.

Lal et al. (2013; PMID: 24039908) report two cases with nonsense RBFOX3 variants, both with initial speech or language delay, and one of which with "Moderate developmetal delay, delayed speech development, mild oral dyspraxia".
Sources: Expert list, Expert Review
Speech apraxia v0.27 PURA Thomas Scerri gene: PURA was added
gene: PURA was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PURA were set to 36117209
Phenotypes for gene: PURA were set to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties, MIM# 616158
Added comment: First reported CAS case with an inherited missense PURA variant (Kaspi et al., 2022; PMID: 36117209). Both proband and parent affected.
Sources: Expert list, Expert Review
Speech apraxia v0.27 PHF21A Thomas Scerri gene: PHF21A was added
gene: PHF21A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: PHF21A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHF21A were set to 36117209
Phenotypes for gene: PHF21A were set to Intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures, MIM# 618725
Review for gene: PHF21A was set to RED
Added comment: First reported CAS case with a de novo frameshift PHF21A variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.27 KDM5C Thomas Scerri gene: KDM5C was added
gene: KDM5C was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KDM5C was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: KDM5C were set to 36117209; 36434256
Phenotypes for gene: KDM5C were set to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, MIM# 300534
Review for gene: KDM5C was set to RED
Added comment: First reported CAS case with a de novo frameshift HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).

Leonardi et al. (2023; PMID: 36434256) report 30 individuals with HNRNPK variants, of which 16 have reported speech delay (including all males with records, and several females). No mention of apraxia or dyspraxia though.

Note: Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type (MIM# 300534) is recorded as autosomal recessive, however female heterozygotes can have milder phenotypes.
Sources: Expert list, Expert Review
Speech apraxia v0.27 HNRNPK Thomas Scerri gene: HNRNPK was added
gene: HNRNPK was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HNRNPK were set to 36117209
Phenotypes for gene: HNRNPK were set to Au-Kline syndrome, MIM# 616580
Review for gene: HNRNPK was set to RED
Added comment: First reported CAS case with a de novo nonsense HNRNPK variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.21 SETD1A Zornitza Stark Marked gene: SETD1A as ready
Speech apraxia v0.21 SETD1A Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.21 SETD1A Zornitza Stark Classified gene: SETD1A as Amber List (moderate evidence)
Speech apraxia v0.21 SETD1A Zornitza Stark Gene: setd1a has been classified as Amber List (Moderate Evidence).
Speech apraxia v0.20 SETBP1 Zornitza Stark Marked gene: SETBP1 as ready
Speech apraxia v0.20 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Speech apraxia v0.20 SETBP1 Zornitza Stark Classified gene: SETBP1 as Green List (high evidence)
Speech apraxia v0.20 SETBP1 Zornitza Stark Gene: setbp1 has been classified as Green List (High Evidence).
Speech apraxia v0.10 ARHGEF9 Zornitza Stark Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Speech apraxia v0.8 ERF Thomas Scerri gene: ERF was added
gene: ERF was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ERF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ERF were set to 36117209; 35761471; 35852485
Phenotypes for gene: ERF were set to Craniosynostosis 4, MIM# 600775
Review for gene: ERF was set to AMBER
Added comment: First two reported CAS cases with a nonsense ERF variant (Kaspi et al., 2022; PMID: 36117209) inherited from mother to proband.

Care et al. (2022; PMID: 35761471) report 5 cases with ERF variants, and of these 3 have speech disorder.

Moddemann et al. (PMID: 35852485) conduct a meta-analysis of 79 independent samples with ERF variants and find 60% have speech delay/impairments.
Sources: Expert list, Expert Review
Speech apraxia v0.8 DIP2C Thomas Scerri gene: DIP2C was added
gene: DIP2C was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: DIP2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DIP2C were set to 36117209; 38421105
Phenotypes for gene: DIP2C were set to Neurodevelopmental disorder (MONDO:0700092), DIP2C-related
Review for gene: DIP2C was set to AMBER
Added comment: First reported CAS proband with a de novo splice DIP2C variant (Kaspi et al., 2022; PMID: 36117209).

Ha et al. (2024; PMID: 38421105) report 23 cases with various DIP2C variants, including the one published by Kaspi et al. (2022; PMID: 36117209). All 23 cases have various speech deficits and two (including the Kaspi et al. (2022) case) are reported having speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 BRPF1 Thomas Scerri gene: BRPF1 was added
gene: BRPF1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: BRPF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRPF1 were set to 36117209; 27939640; 38346666
Phenotypes for gene: BRPF1 were set to Intellectual developmental disorder with dysmorphic facies and ptosis, MIM# 617333
Review for gene: BRPF1 was set to GREEN
Added comment: First reported CAS proband with a de novo missense BRPF1 variant (Kaspi et al., 2022; PMID: 36117209).

Yan et al. (2017; PMID: 27939640) reported 10 independent cases with de novo or inherited BRPF1 variants and with a range of speech and language deficits, including one proband with speech apraxia (proband 4, Table S1).

Morison et al. (2024; PMID: 38346666) report 15 new cases with mostly de novo BRPF1 variants and a range of speech deficits, including 3 specifically with speech apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 ARHGEF9 Thomas Scerri gene: ARHGEF9 was added
gene: ARHGEF9 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ARHGEF9 were set to 36117209
Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM# 300607
Review for gene: ARHGEF9 was set to RED
Added comment: Only reported CAS proband with a de novo nonsense ARHGEF9 variant (Kaspi et al., 2022; PMID: 36117209).
Sources: Expert list, Expert Review
Speech apraxia v0.8 ZNF142 Thomas Scerri gene: ZNF142 was added
gene: ZNF142 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZNF142 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZNF142 were set to 32345733; 31036918; 34531528; 35616059
Phenotypes for gene: ZNF142 were set to Neurodevelopmental disorder with impaired speech and hyperkinetic movements, MIM# 618425
Review for gene: ZNF142 was set to AMBER
Added comment: A reported CAS proband with compound heterozygous missenses ZNF142 variants (Hildebrand et al., 2020; PMID: 32345733).

Khan et al. (2019, PMID: 31036918) report 7 cases with compound heterozygous or else homozygous LoF or missense ZNF142 variants for which the cases have a range of speech deficits including speech apraxia in one case.

Kameyama et al. (2020, PMID: 34531528) report two brothers with biallelic LoF ZNF142 variants for which the cases have speech deficits.

Christensen et al. (2022; PMID: 35616059) report a further 26 individuals with biallelic ZNF142 variants for which the cases have a range of speech deficits.
Sources: Expert list, Expert Review
Speech apraxia v0.8 UPF2 Thomas Scerri gene: UPF2 was added
gene: UPF2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: UPF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UPF2 were set to 32345733; 31585809
Phenotypes for gene: UPF2 were set to Neurodevelopmental disorder (MONDO:0700092), UPF2-related
Review for gene: UPF2 was set to RED
Added comment: A CAS proband with a de novo LoF UPF2 variant (Hildebrand et al., 2020; PMID: 32345733).

Johnson et al. (2019; PMID: 31585809) report 3 independent cases with LoF UPF2 variants and a range of speech deficits, including speech apraxia in one of the cases (although the speech disorder had resolved to a mild phonological disorder at later testing).
Sources: Expert list, Expert Review
Speech apraxia v0.8 POGZ Thomas Scerri gene: POGZ was added
gene: POGZ was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 32345733; 35052493
Phenotypes for gene: POGZ were set to White-Sutton syndrome, MIM# 616364
Review for gene: POGZ was set to RED
Added comment: Only reported CAS proband with a de novo missense POGZ variant (Hildebrand et al., 2020; PMID: 32345733).

Nagy et al. (2022; PMID: 35052493) reported 117 cases from a meta-analysis and found that "the most common symptoms were speech delay in 88%". This is not strong enough evidence to be supporting evidence for speech apraxia per se.
Sources: Expert list, Expert Review
Speech apraxia v0.8 MEIS2 Thomas Scerri gene: MEIS2 was added
gene: MEIS2 was added to Speech apraxia. Sources: Expert Review,Expert list
Mode of inheritance for gene: MEIS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEIS2 were set to 32345733; 30055086
Phenotypes for gene: MEIS2 were set to Cleft palate, cardiac defects, and impaired intellectual development, MIM# 600987
Review for gene: MEIS2 was set to AMBER
Added comment: First reported CAS proband with a LoF MEI2 variant (Hildebrand et al., 2020; PMID: 32345733).

Douglas et al. (2018; PMID: 30055086) report 3 new cases with de novo missense variants and 2 previously published deletion and nonsense variants. All cases have a range of differently worded speech problems, and one has verbal apraxia.
Sources: Expert Review, Expert list
Speech apraxia v0.8 GNB1 Thomas Scerri gene: GNB1 was added
gene: GNB1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 32345733
Phenotypes for gene: GNB1 were set to Intellectual developmental disorder, autosomal dominant 42, MIM# 616973
Review for gene: GNB1 was set to RED
Added comment: Only reported CAS proband with a de novo nonsense GNB1 variant (Hildebrand et al., 2020; PMID: 32345733).
Sources: Expert list, Expert Review
Speech apraxia v0.8 GNAO1 Thomas Scerri gene: GNAO1 was added
gene: GNAO1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAO1 were set to 32345733; 35722775; 38881224
Phenotypes for gene: GNAO1 were set to Developmental and epileptic encephalopathy 17, MIM# 615473; Neurodevelopmental disorder with involuntary movements, MIM# 617493
Review for gene: GNAO1 was set to AMBER
Added comment: First reported CAS proband with a de novo missense GNAO1 variant (Hildebrand et al., 2020; PMID: 32345733).

These additional cases are less clear for speech apraxia:

Wirth et al. (2020; PMID: 35722775) reported twenty-four independent cases with a range of de novo and inherited variants, including missense and nonsense, for which a speech disorder (dysarthria) was reported for 19 individuals.

Lasa-Aranzasti et al. (2024; PMID: 38881224) report eighteen independent cases and find "all patients developed some type of nonverbal communication, but only four acquired verbal language."
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: AMBER
Speech apraxia v0.8 SETD1A Thomas Scerri edited their review of gene: SETD1A: Changed rating: RED
Speech apraxia v0.8 SETD1A Thomas Scerri changed review comment from: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)".
Sources: Expert list, Expert Review; to: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)". However, only one proband was explicitly recorded with speech apraxia (proband 14; supplementary Table 1).

Sources: Expert list, Expert Review
Speech apraxia v0.8 EBF3 Thomas Scerri gene: EBF3 was added
gene: EBF3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EBF3 were set to 32345733; 28017372
Phenotypes for gene: EBF3 were set to Hypotonia, ataxia, and delayed development syndrome, MIM# 617330
Review for gene: EBF3 was set to GREEN
Added comment: First proband with a de novo nonsense EBF3 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Chao et al., (2017; PMID: 28017372) report three independent cases with de novo missense variants (all three curiously substituting the same amino acid). All three cases have "expressive speech disorder (3/3)" and a range of dysarthria and apraxia.
Sources: Expert list, Expert Review
Speech apraxia v0.8 DDX3X Thomas Scerri gene: DDX3X was added
gene: DDX3X was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: DDX3X were set to 32345733; 36117209; 37904618
Phenotypes for gene: DDX3X were set to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, MIM# 300958
Review for gene: DDX3X was set to GREEN
Added comment: First proband with a de novo LoF DDX3X variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Second proband with a de novo LoF DDX3X variant reported for CAS (Kaspi et al., 2022; PMID: 36117209)

Parra et al. (2024; PMID: 37904618) report thirty-four independent probands with DDX3X mutations for which "the most frequent clinical features (>70%) identified in these patients included speech dyspraxia (88.2%)".
Sources: Expert list, Expert Review
Speech apraxia v0.8 CDK13 Thomas Scerri gene: CDK13 was added
gene: CDK13 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDK13 were set to 32345733; 36599938
Phenotypes for gene: CDK13 were set to Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder, MIM# 617360
Review for gene: CDK13 was set to GREEN
Added comment: First proband with a de novo missense CDK13 variant reported for CAS (Hildebrand et al., 2020; PMID: 32345733).

Morison et al. (2023; PMID: 36599938) report 41 cases (with 33 novel variants) and find "most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22)."
Sources: Expert list, Expert Review
Speech apraxia v0.8 ZFHX4 Thomas Scerri gene: ZFHX4 was added
gene: ZFHX4 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: ZFHX4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZFHX4 were set to 29463886; 34461323
Phenotypes for gene: ZFHX4 were set to Neurodevelopmental disorder (MONDO:0700092), ZFHX4-related
Review for gene: ZFHX4 was set to RED
Added comment: First proband with splice acceptor ZFHX4 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fontana et al. (2021; PMID: 34461323) report a similar splice region variant in ZFHX4 for a proband with a neuropsychological phenotype, and summarise other probands with deletions or point mutations and associated phenotypes. Only one of these has a recorded speech phenotype. Overall this paper doesn't add strong evidence for a link between speech apraxia and ZFHX4.
Sources: Expert list, Expert Review
Speech apraxia v0.8 WDR5 Thomas Scerri gene: WDR5 was added
gene: WDR5 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: WDR5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR5 were set to 29463886; 36408368
Phenotypes for gene: WDR5 were set to Neurodevelopmental disorder (MONDO:0700092), WDR5-related
Review for gene: WDR5 was set to GREEN
Added comment: First proband with a de novo missense WDR5 variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Blok et al. (2022; PMID: 36408368) studied "11 unrelated individuals with six different rare de novo germline missense variants in WDR5; one identical variant was found in five individuals and another variant in two individuals. All individuals had neurodevelopmental disorders including speech/language delays (n = 11). Speech delays were reported in all individuals, including nasal speech, developmental language disorders, verbal dyspraxia, and persistent stuttering."
Sources: Expert list, Expert Review
Speech apraxia v0.8 TNRC6B Thomas Scerri gene: TNRC6B was added
gene: TNRC6B was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: TNRC6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNRC6B were set to 29463886; 32152250; 38300321; 38404251
Phenotypes for gene: TNRC6B were set to Global developmental delay with speech and behavioral abnormalities, MIM# 619243
Review for gene: TNRC6B was set to GREEN
Added comment: First proband with a LoF TNRC6B variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Granadillo et al., (2020; PMID: 32152250) studied seventeen further probands with LoF TNRC6B variants and found "speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17)".

Yahia et al., (2024; PMID: 38300321) looked at a Swedish cohort with severe developmental language disorder and find another case with a LoF variant in TNRC6B.

Yang et al., (2024; PMID: 38404251) report two independent cases with speech delay/abnormalities carrying LoF variants in TNRC6B.
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETD1A Thomas Scerri gene: SETD1A was added
gene: SETD1A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETD1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD1A were set to 29463886; 32346159
Phenotypes for gene: SETD1A were set to Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM# 619056
Review for gene: SETD1A was set to GREEN
Added comment: First proband with a LoF SETD1A variant reported for CAS (Eising et al., 2019; PMID: 29463886).

Fifteen further independent probands with LoF SETD1A variants were investigated (Kummeling et al., 2021; PMID: 32346159) and "global DD was reported in 14/15 individuals, including delayed speech and language development (14/14) and motor development (13/14)".
Sources: Expert list, Expert Review
Speech apraxia v0.8 SETBP1 Thomas Scerri gene: SETBP1 was added
gene: SETBP1 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETBP1 were set to 29463886; 33907317
Phenotypes for gene: SETBP1 were set to Intellectual developmental disorder, autosomal dominant 29, MIM# 616078
Review for gene: SETBP1 was set to GREEN
Added comment: First proband with LoF SETBP1 variant reported for CAS (Eising et al., 2019; PMID: 29463886)

Thirty one further probands with LoF SETBP1 variants studied (Morgan et al., 2019; PMID: 33907317) revealing that "Protracted and aberrant speech development was consistently seen, regardless of motor or intellectual ability. We expand the linguistic phenotype associated with SETBP1 LoF syndrome (SETBP1 haploinsufficiency disorder), revealing a striking speech presentation that implicates both motor (CAS, dysarthria) and language (phonological errors) systems, with CAS (80%) being the most common diagnosis.".
Sources: Expert list, Expert Review
Speech apraxia v0.0 MKL2 Thomas Scerri gene: MKL2 was added
gene: MKL2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: MKL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MKL2 were set to 29463886; 37013900; 38366112
Phenotypes for gene: MKL2 were set to Childhood apraxia of speech; see comments.
Penetrance for gene: MKL2 were set to Complete
Added comment: p.R104G and p.A91P reported as a gain of function (JC Andrews et al., 2023).

Additional phenotypes: ID, GDD, CAS, mild dysmorphic features, impulse control issues. AT Morgan et al., (2024).
Sources: Expert list, Expert Review
Speech apraxia v0.0 KAT6A Thomas Scerri gene: KAT6A was added
gene: KAT6A was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 35892268; 38366112; 30245513
Phenotypes for gene: KAT6A were set to Childhood apraxia of speech; see comments.
Penetrance for gene: KAT6A were set to Complete
Review for gene: KAT6A was set to GREEN
Added comment: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population. AT Morgan et al. (2024).
Sources: Expert list, Expert Review
Speech apraxia v0.0 CHD3 Thomas Scerri gene: CHD3 was added
gene: CHD3 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to PMID: 30397230; 38366112; 35346573
Penetrance for gene: CHD3 were set to Complete
Review for gene: CHD3 was set to GREEN
Added comment: Variant p.Leu915Phe yielded increased activity (PMID: 30397230).
Evidence of reduced penetrance and variable expressivity (PMID: 35346573).
Sources: Expert list, Expert Review
Speech apraxia v0.0 FOXP2 Thomas Scerri gene: FOXP2 was added
gene: FOXP2 was added to Speech apraxia. Sources: Expert list,Expert Review
Mode of inheritance for gene: FOXP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXP2 were set to PMID: 11586359; 36328423; 38366112
Phenotypes for gene: FOXP2 were set to Childhood apraxia of speech
Penetrance for gene: FOXP2 were set to Complete
Review for gene: FOXP2 was set to GREEN
Added comment: Sources: Expert list, Expert Review