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| Speech apraxia v0.38 | CHD3 |
Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia. Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia.; to: First reported CAS case with a de novo CHD3 missense variant (Eising et al., 2019; PMID: 29463886). Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia. Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia. |
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| Speech apraxia v0.31 | KAT6A |
Thomas Scerri changed review comment from: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review; to: First reported CAS case with a KAT6A splice acceptor variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with KAT6A variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases with KAT6A variants and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | KAT6A |
Thomas Scerri changed review comment from: Additional phenotypes: ID, vision impairment, GI dysfunction, sleep disturbance, ASD, majority minimally verbal & rely on alternate communication. Rates of epilepsy, ADHD, CP higher than typical population (PMID: 38366112). Sources: Expert list, Expert Review; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Kennedy et al. (2019; PMID: 30245513) examined 76 cases (including 52 new cases) with CHD3 variants and found speech delay was a core feature, and report 1 case diagnosed with oromotor dyspraxia. St John et al. (2022; PMID: 35892268) examined 49 cases and found "Verbal participants (13/49) displayed complex and co-occurring speech diagnoses regarding the perception/production of speech sounds, including phonological impairment (i.e., linguistic deficits) and speech apraxia (i.e., motor planning/programming deficits), which significantly impacted intelligibility. Receptive/expressive language and adaptive functioning were also severely impaired." In detail, "Across the 13 verbal participants, speech profiles, and intelligibility were varied (Table 2). 10/13 verbal participants were female (77%). 11/13 had delayed speech milestones, some not achieving first words until >18 months and others not combining words until >8 years of age. Verbal participants had a range of speech disorder subtypes, and most had at least two diagnoses (Figure 1c). Phonological delay was most common (8/13, 63%), followed by phonological disorder (7/13, 54%) and CAS (7/13, 54%), but all three conditions always co-occurred with at least one other speech diagnosis. " Sources: Expert list, Expert Review |
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| Speech apraxia v0.31 | CHD3 |
Thomas Scerri changed review comment from: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: First reported CAS case with a de novo missense CHD3 variant (Eising et al., 2019; PMID: 29463886). Snijders Blok et al. (2018; PMID: 30397230) examined 35 cases with CHD3 variants. The index case was diagnosed with severe speech apraxia. Van der Spek et al. (2022; PMID: 35346573) examined 21 families with CHD3 variants and found at least 2 independent cases with speech dyspraxia. |
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| Speech apraxia v0.8 | CHD3 | Zornitza Stark Marked gene: CHD3 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | CHD3 | Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.8 | CHD3 | Zornitza Stark Phenotypes for gene: CHD3 were changed from to Snijders Blok-Campeau syndrome MIM#618205 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.7 | CHD3 | Zornitza Stark Classified gene: CHD3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.7 | CHD3 | Zornitza Stark Gene: chd3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.6 | CHD3 | Zornitza Stark reviewed gene: CHD3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30397230; Phenotypes: Snijders Blok-Campeau syndrome MIM#618205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112).; to: Additional phenotypes: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri edited their review of gene: CHD3: Changed publications: 30397230, 38366112, 35346573 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. (PMID: 38366112). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri changed review comment from: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; to: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al., (2024). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri edited their review of gene: CHD3: Added comment: ID/DD, macrocephaly, prominent forehead, hypertelorism, hypotonia, joint laxity, severity of neurologic deficits & presence of non-neurologic features are variable. Autistic features are commonly reported. AT Morgan et al. (2024).; Changed phenotypes: Childhood apraxia of speech, see comments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Speech apraxia v0.0 | CHD3 | Thomas Scerri edited their review of gene: CHD3: Changed phenotypes: Childhood apraxia of speech | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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