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| Craniosynostosis v1.67 | MAP3K20 |
Zornitza Stark gene: MAP3K20 was added gene: MAP3K20 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: MAP3K20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAP3K20 were set to 38451290 Phenotypes for gene: MAP3K20 were set to Syndromic disease, MONDO:0002254, MAP3K20-related Review for gene: MAP3K20 was set to GREEN Added comment: PMID 38451290: five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. Sources: Literature |
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| Craniosynostosis v1.61 | MAN2B1 |
Yetong Chen gene: MAN2B1 was added gene: MAN2B1 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAN2B1 were set to 34429528; 33288889; 35242565 Phenotypes for gene: MAN2B1 were set to Mannosidosis, alpha-, types I and II, MIM# 248500 Review for gene: MAN2B1 was set to GREEN Added comment: A total of 3 unrelated individuals are reported. PMID 34429528 reports a patient (case 1) with compound heterozygous MAN2B1 variants (c.1830+1G>C and c.2248C>T) who had craniosynostosis. PMID 33288889 reports a patient with recessive MAN2B1 variants (c.1055 T > C,p.Leu352Pro) who presented craniosynostosis. PMID 35242565 reports a patient (patient 3) with compound heterozygous MAN2B1 variants (c.2245C > T, p.Arg749Trp and c.2355G > A, p.Thr785*) who had craniosynostosis. Sources: Expert Review |
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| Craniosynostosis v1.61 | FBXO11 |
Yetong Chen gene: FBXO11 was added gene: FBXO11 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: FBXO11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FBXO11 were set to 34429528; 30057029 Phenotypes for gene: FBXO11 were set to intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, MIM# 618089 Review for gene: FBXO11 was set to GREEN Added comment: A total of 3 unrelated individuals are reported. PMID 34429528 reports a patient with a de novo FBXO11 variant (c.2731_2732insGACA, p.Thr911Argfs*5) who had craniosynostosis. PMID 30057029 reports 2 patients (patients 5 and 11) with monoallelic FBXO11 variants (c.2518T>C, p.Ser840Pro and c.1042−1G>C with unknown p.) who had sagittal and metopic craniosynostosis, respectively. Sources: Expert Review |
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| Craniosynostosis v1.56 | CDK13 |
Yetong Chen changed review comment from: A total of 4 unrelated individuals are reported. PMID 34429528 reports a patient with a monoallelic CDK13 variant (c.2563G>C, p.Asp855His) who had metopic synostosis. PMID 28807008 mentioned 2 patients with craniosynostosis were identified from 9 individuals with CDK13 variants. However, detailed information about the 2 patients is not provided. PMID 33288889 reported a patient with a CDK13 variant (c.2524 A > G, p.Asn842Asp) who presented with craniosynostosis. Sources: Expert Review; to: A total of 4 unrelated individuals are reported. PMID 34429528 reports a patient with a monoallelic CDK13 variant (c.2563G>C, p.Asp855His) who had metopic synostosis. PMID 28807008 mentions 2 patients with craniosynostosis were identified from 9 individuals with CDK13 variants. However, detailed information about the 2 patients is not provided. PMID 33288889 reports a patient with a CDK13 variant (c.2524 A > G, p.Asn842Asp) who presented with craniosynostosis. Sources: Expert Review |
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| Craniosynostosis v1.56 | CDK13 |
Yetong Chen gene: CDK13 was added gene: CDK13 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: CDK13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CDK13 were set to 34429528; 28807008; 33288889 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: A total of 4 unrelated individuals are reported. PMID 34429528 reports a patient with a monoallelic CDK13 variant (c.2563G>C, p.Asp855His) who had metopic synostosis. PMID 28807008 mentioned 2 patients with craniosynostosis were identified from 9 individuals with CDK13 variants. However, detailed information about the 2 patients is not provided. PMID 33288889 reported a patient with a CDK13 variant (c.2524 A > G, p.Asn842Asp) who presented with craniosynostosis. Sources: Expert Review |
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| Craniosynostosis v1.56 | ARID1B |
Yetong Chen gene: ARID1B was added gene: ARID1B was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARID1B were set to 36118902; 34429528; 27474218; 32530565 Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, MIM# 135900 Review for gene: ARID1B was set to GREEN Added comment: A total of 4 unrelated individuals are reported. PMID 36118902 reports a patient with an ARID1B variant (chr6:g.157431670_157431676 delCCAGTCA) who presented with sagittal craniosynostosis. PMID 34429528 identifies a patient (case 16) with an ARID1B variant (c.3594delinsCCCCCA) by screening 127 families classified with craniosynostosis. PMID 27474218 reported a patient (patient 10) with an ARID1B variant (c.1468_1472delTGGGC) who presented with craniosynostosis. PMID 32530565 listed a patient (OKI-047-1 M) harbouring an ARID1B variant (c.2277delC) who had trigonocephaly. Sources: Expert Review |
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| Craniosynostosis v1.56 | AHDC1 |
Yetong Chen gene: AHDC1 was added gene: AHDC1 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: AHDC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AHDC1 were set to 27884935; 30858058; 30152016; 27148574; 33288889 Phenotypes for gene: AHDC1 were set to Xia-Gibbs syndrome, MIM# 615829 Review for gene: AHDC1 was set to GREEN Added comment: More than 3 unrelated individuals are reported. PMID 27884935 scanned craniosynostosis patients and identified an AHDC1 variant (c.2373_2374delTG, p.C791fs*57) from a patient with craniosynostosis. PMID 30858058 reports a patient with a heterozygous AHDC1 variant (c.4370 A>G, p.Asp1457Gly) who had craniosynostosis. PMID 30152016 reports a patient (patient 1) with a heterozygous AHDC1 variant (c.2473C>T; p.Q825*) who had craniosynostosis. PMID 27148574 reports a patient (patient 3) with an AHDC1 variant (c.1881delG p.Q627Hfs*105) who had sagittal craniosynostosis. PMID 33288889: Of 94 individuals with syndromic craniosynostosis, 2 individuals carried AHDC1 variants (c.3185_3186del p.(Thr1062Serfs*63) and c.2772del p.(Arg925Glufs*7), respectively). Sources: Expert Review |
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| Craniosynostosis v1.55 | RARA |
Krithika Murali changed review comment from: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of trio exome sequencing data. The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure. The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain. Both affected individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs) - other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia) - renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency Sources: Literature; to: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of trio exome sequencing data. The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure. The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain. Both affected individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - limb anomalies (rocker-bottom feet, bowing of the legs, and short upper and lower limbs) - other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia) - renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency Sources: Literature |
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| Craniosynostosis v1.55 | RARA |
Krithika Murali changed review comment from: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of exome sequencing data. The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure. The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain. Both affected individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs) - other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia) - renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency Sources: Literature; to: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of trio exome sequencing data. The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure. The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain. Both affected individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs) - other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia) - renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency Sources: Literature |
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| Craniosynostosis v1.55 | RARA |
Krithika Murali gene: RARA was added gene: RARA was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: RARA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RARA were set to PMID: 37086723 Phenotypes for gene: RARA were set to Craniosynostosis - MONDO:0015469 Review for gene: RARA was set to AMBER Added comment: PMID: 37086723 - a study of 526 probands with syndromic craniosynostosis and analysis of exome sequencing data. The authors report 2 unrelated individuals with a similar phenotype and a recurrent de novo heterozygous missense RARA variant - c.865G>A; p.(Gly289Arg). Gain of function mechanism postulated. No functional studies. Gene encodes retinoic acid receptor with some phenotypic features overlapping with prenatal retionic acid teratogen exposure. The variant is absent from gnomAD, major GS (125), highly conserved residue in the hormone receptor domain. Both affected individuals had severe craniosynostosis (sagittal or bicoronal). Other shared phenotypic features included: - limb anomalies (rocker-bottom feet, bowing of the legs, and short uppe rand lower limbs) - other craniofacial anomalies (microtia,conductive hearing loss, ankyloglossia, esotropia, hypo-plastic nasal bones, and oligodontia) - renal dysplasia with cysts, tracheomalacia, pulmonary arterial hypertension, developmental delays, hypotonia, cryptorchidism, seizures, adrenal insufficiency Sources: Literature |
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| Craniosynostosis v1.47 | PRRX1 |
Calder Hamill gene: PRRX1 was added gene: PRRX1 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: PRRX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRRX1 were set to 36980886 Phenotypes for gene: PRRX1 were set to Craniosynostosis Penetrance for gene: PRRX1 were set to Incomplete Mode of pathogenicity for gene: PRRX1 was set to Other Review for gene: PRRX1 was set to GREEN Added comment: > 17 individuals with Craniosynostosis from 14 families had been found to have rare heterozygous variants in PRRX1, predicting loss of function variants or missense variants affecting the homeodomain. > These consisted of three de novo variants, but for the majority of cases the variant was inherited from an unaffected parent (Tooze, R.S.; Calpena, E.; Weber, A.; Wilson, L.C.; Twigg, S.R.F.; Wilkie, A.O.M. Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels. Genes 2023, 14, 615. https://doi.org/10.3390/ genes14030615) Supporting evidence: > Post-natal calvarial stem cells expressing Prrx1 have been shown to reside exclusively in the calvarial suture niche, suggesting a requirement for PRRX1 regarding suture patency during early development. (Wilk, K.; Yeh, S.A.; Mortensen, L.J.; Ghaffarigarakani, S.; Lombardo, C.M.; Bassir, S.H.; Aldawood, Z.A.; Lin, C.P.; Intini, G. Postnatal Calvarial Skeletal Stem Cells Expressing PRX1 Reside Exclusively in the Calvarial Sutures and Are Required for Bone Regeneration. Stem Cell Rep. 2017, 8, 933–946.) >Prrx1 has been shown to be widely expressed within the mouse coronal suture. (Farmer, D.T.; Mlcochova, H.; Zhou, Y.; Koelling, N.; Wang, G.; Ashley, N.; Bugacov, H.; Chen, H.J.; Parvez, R.; Tseng, K.C.; et al. The developing mouse coronal suture at single-cell resolution. Nat. Commun. 2021, 12, 4797) Sources: Literature |
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| Craniosynostosis v1.30 | CHD7 |
Ee Ming Wong changed review comment from: - Siakallis et al (2019): 18-month old boy diagnosed with CHARGE syndrome and subsequently diagnosed with bicoronal craniosynostosis, premature synostosis of the left lambdoid and squamous sutures resulting in a turricephalic appearance of the cranial vault. He was found to carry a CHD7 stopgain variant. - Tonne et al (2020): De novo CHD7 frameshift variant identified in individual with CHARGE syndrome and late occurrence of craniosynostosis at 5 years. - De Luca et al (2021): De novo CHD7 stopgain variant identified in one newborn with CHARGE syndrome with bi-coronal craniosynostosis. Authors considered the diagnosis of craniosynostosis to be potentially independant of CHARGE syndrome. Sources: Literature; to: - Siakallis et al (2019): 18-month old boy diagnosed with CHARGE syndrome and subsequently diagnosed with bicoronal craniosynostosis, premature synostosis of the left lambdoid and squamous sutures resulting in a turricephalic appearance of the cranial vault. He was found to carry a CHD7 stopgain variant. - Tonne et al (2020): De novo CHD7 frameshift variant identified in individual with CHARGE syndrome and late occurrence of craniosynostosis at 5 years. - De Luca et al (2021): De novo CHD7 stopgain variant identified in one newborn with CHARGE syndrome with bi-coronal craniosynostosis. Authors considered the diagnosis of craniosynostosis to be potentially independant of CHARGE syndrome. Sources: Literature |
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| Craniosynostosis v1.30 | CHD7 |
Ee Ming Wong changed review comment from: - Siakallis et al (2019): 18-month old boy diagnosed with CHARGE syndrome and subsequently diagnosed with bicoronal craniosynostosis, premature synostosis of the left lambdoid and squamous sutures resulting in a turricephalic appearance of the cranial vault. He was found to carry a CHD7 stopgain variant. - Tonne et al (2020): De novo CHD7 frameshift variant identified in individual with CHARGE syndrome and late occurrence of craniosynostosis at 5 years. - De Luca et al (2021): De novo CHD7 stopgain variant identified in one newborn with CHARGE syndrome with bi-coronal craniosynostosis. Authors considered the diagnosis of craniosynostosis to be potentially independant of CHARGE syndrome. Sources: Literature; to: - Siakallis et al (2019): 18-month old boy diagnosed with CHARGE syndrome and subsequently diagnosed with bicoronal craniosynostosis, premature synostosis of the left lambdoid and squamous sutures resulting in a turricephalic appearance of the cranial vault. He was found to carry a CHD7 stopgain variant. - Tonne et al (2020): De novo CHD7 frameshift variant identified in individual with CHARGE syndrome and late occurrence of craniosynostosis at 5 years. - De Luca et al (2021): De novo CHD7 stopgain variant identified in one newborn with CHARGE syndrome with bi-coronal craniosynostosis. Authors considered the diagnosis of craniosynostosis to be potentially independant of CHARGE syndrome. Sources: Literature |
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| Craniosynostosis v1.30 | CHD7 |
Ee Ming Wong gene: CHD7 was added gene: CHD7 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHD7 were set to PMID: 33844462; 30498854; 33288889 Phenotypes for gene: CHD7 were set to CHARGE syndrome; bi-coronal craniosynostosis; premature synostosis of the left lambdoid and squamous sutures Penetrance for gene: CHD7 were set to Complete Review for gene: CHD7 was set to GREEN gene: CHD7 was marked as current diagnostic Added comment: - Siakallis et al (2019): 18-month old boy diagnosed with CHARGE syndrome and subsequently diagnosed with bicoronal craniosynostosis, premature synostosis of the left lambdoid and squamous sutures resulting in a turricephalic appearance of the cranial vault. He was found to carry a CHD7 stopgain variant. - Tonne et al (2020): De novo CHD7 frameshift variant identified in individual with CHARGE syndrome and late occurrence of craniosynostosis at 5 years. - De Luca et al (2021): De novo CHD7 stopgain variant identified in one newborn with CHARGE syndrome with bi-coronal craniosynostosis. Authors considered the diagnosis of craniosynostosis to be potentially independant of CHARGE syndrome. Sources: Literature |
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| Craniosynostosis v1.27 | GNB1 |
Zornitza Stark gene: GNB1 was added gene: GNB1 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GNB1 were set to 32134617 Phenotypes for gene: GNB1 were set to Intellectual developmental disorder, autosomal dominant 42, MIM# 616973 Review for gene: GNB1 was set to GREEN Added comment: Over 50 affected individuals reported. Cleft palate present in >20%. Sources: Literature |
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| Craniosynostosis v1.18 | LTBP1 |
Chern Lim gene: LTBP1 was added gene: LTBP1 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LTBP1 were set to 33991472 Phenotypes for gene: LTBP1 were set to cutis laxa syndrome Review for gene: LTBP1 was set to GREEN gene: LTBP1 was marked as current diagnostic Added comment: PMID:33991472 - Premature truncating variants in multiple affected individuals from 4 unrelated consanguineous families. - Affected individuals present with connective tissue features (cutis laxa and inguinal hernia), craniofacial dysmorphology, variable heart defects, and prominent skeletal features (craniosynostosis, short stature, brachydactyly, and syndactyly). - Functional studies done on patient fibroblasts and zebrafish models. Sources: Literature |
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| Craniosynostosis v1.14 | SIX1 |
Zornitza Stark gene: SIX1 was added gene: SIX1 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: SIX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SIX1 were set to 33436522 Phenotypes for gene: SIX1 were set to Sagittal synostosis; Multi-suture synostosis Review for gene: SIX1 was set to GREEN Added comment: Calpena et al 2021 (PMID:33436522) identified 7 families in which the proband had craniosynostosis (affecting at least the sagittal suture in all cases) and a heterozygous SIX1 variant (4 nonsense + 3 missense in highly conserved residues of SIX domain or homeodomain). SIX1 mutations (mostly missense) were previously described in branchio-otic syndrome (BOS). Patients and carriers in the extended family variably had features of BOS (including branchial cysts, ear tags or pits, and hearing loss), but there were also several non-penetrant heterozygous individuals, indicating variation in expressivity. SIX1 analysis is therefore particularly indicated in individuals with either (1) additional BOS features or (2) sagittal+bilambdoid synostosis. Sources: Literature |
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| Craniosynostosis v1.12 | TRAF7 |
Zornitza Stark gene: TRAF7 was added gene: TRAF7 was added to Craniosynostosis. Sources: Expert Review Mode of inheritance for gene: TRAF7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRAF7 were set to 32459067; 32376980; 29961569 Phenotypes for gene: TRAF7 were set to Cardiac, facial, and digital anomalies with developmental delay, MIM# 618164 Review for gene: TRAF7 was set to GREEN Added comment: Over 50 affected individuals reported. Craniofacial abnormalities are common, including craniosynostosis in more than 3. Sources: Expert Review |
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| Craniosynostosis v0.132 | PJA1 |
Zornitza Stark gene: PJA1 was added gene: PJA1 was added to Craniosynostosis. Sources: Literature founder tags were added to gene: PJA1. Mode of inheritance for gene: PJA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PJA1 were set to 32530565 Phenotypes for gene: PJA1 were set to Intellectual disability; trigonocephaly Review for gene: PJA1 was set to AMBER Added comment: Recurrent variant, p.Arg376Cys, reported in 7 Japanese individuals, supportive mouse model. Individuals shared a common haplotype, suggestive of founder effect. Sources: Literature |
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| Craniosynostosis v0.120 | TMCO1 |
Zornitza Stark gene: TMCO1 was added gene: TMCO1 was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: TMCO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMCO1 were set to 20018682; 24424126; 24194475 Phenotypes for gene: TMCO1 were set to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980 Review for gene: TMCO1 was set to AMBER Added comment: Craniosynostosis reported in a small number of affected individuals, also note founder mutation in Amish. Sources: Expert list |
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| Craniosynostosis v0.118 | TFAP2B |
Zornitza Stark gene: TFAP2B was added gene: TFAP2B was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: TFAP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TFAP2B were set to 31292255 Phenotypes for gene: TFAP2B were set to Syndromic craniosynostosis Review for gene: TFAP2B was set to GREEN Added comment: Four individuals reported in PMID: 31292255 (Correction in PMID: 31405973) as part of a craniosynostosis cohort: 2 de novo and 2 inherited. There is evidence for reduced penetrance as in one case the variant was inherited from an unaffected parent (affected parent for the other inherited variant). Sources: Expert list |
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| Craniosynostosis v0.109 | PHEX |
Zornitza Stark gene: PHEX was added gene: PHEX was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: PHEX was set to Other Publications for gene: PHEX were set to 19242361; 17551721 Phenotypes for gene: PHEX were set to Hypophosphatemic rickets, X-linked dominant, MIM# 307800 Review for gene: PHEX was set to GREEN Added comment: Craniosynostosis reported in around ~40% of affected individuals. Sources: Expert list |
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| Craniosynostosis v0.102 | IDUA | Zornitza Stark Marked gene: IDUA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Craniosynostosis v0.102 | IDUA | Zornitza Stark Gene: idua has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Craniosynostosis v0.102 | IDUA | Zornitza Stark Classified gene: IDUA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Craniosynostosis v0.102 | IDUA | Zornitza Stark Gene: idua has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Craniosynostosis v0.101 | IDUA |
Zornitza Stark gene: IDUA was added gene: IDUA was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IDUA were set to 23917744 Phenotypes for gene: IDUA were set to Mucopolysaccharidosis Ih/s (Hurler syndrome) 607014; 607016 Review for gene: IDUA was set to GREEN Added comment: Craniosynostosis of at least one suture was present in 77% of 47 MPS individuals (types I,II,VI, VII). >3 with IDUA, IDS, ARSB variants. Sources: Expert list |
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| Craniosynostosis v0.99 | IDS |
Zornitza Stark gene: IDS was added gene: IDS was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: IDS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IDS were set to 15314824 Phenotypes for gene: IDS were set to Mucopolysaccharidosis II (MPS2, Hunter syndrome) 309900 Review for gene: IDS was set to GREEN Added comment: Craniosynostosis of at least one suture reported as present in 77% of 47 MPS individuals (types I,II,VI, VII). >3 with IDUA, IDS, ARSB variants. Sources: Expert list |
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| Craniosynostosis v0.86 | CTSK |
Zornitza Stark gene: CTSK was added gene: CTSK was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: CTSK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTSK were set to 21968522; 23175007 Phenotypes for gene: CTSK were set to Pycnodysostosis, MIM#265800 Review for gene: CTSK was set to GREEN Added comment: Craniosynostosis described in some individuals. Sources: Expert list |
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| Craniosynostosis v0.82 | ARSB |
Zornitza Stark gene: ARSB was added gene: ARSB was added to Craniosynostosis. Sources: Expert list Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ARSB were set to Mucopolysaccharidosis VI (MPS6, MIM# 253200 Review for gene: ARSB was set to GREEN Added comment: Synostosis of at least one suture was present in 77% of 47 MPS cases (types I,II,VI, VII). >3 cases with IDUA, IDS, ARSB variants. Sources: Expert list |
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| Craniosynostosis v0.73 | ZNF462 |
Tiong Tan gene: ZNF462 was added gene: ZNF462 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: ZNF462 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZNF462 were set to 28513610 Phenotypes for gene: ZNF462 were set to WEISS-KRUSZKA SYNDROME Penetrance for gene: ZNF462 were set to Complete Review for gene: ZNF462 was set to GREEN Added comment: Craniosynostosis observed in 38% of affected individuals Sources: Literature |
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| Craniosynostosis v0.56 | SHOC2 |
Tiong Tan gene: SHOC2 was added gene: SHOC2 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: SHOC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SHOC2 were set to 28650561; 25123707 Phenotypes for gene: SHOC2 were set to Noonan syndrome with loose anagen hair Penetrance for gene: SHOC2 were set to Complete Mode of pathogenicity for gene: SHOC2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SHOC2 was set to AMBER Added comment: Two unrelated individuals with SHOC2-related Noonan syndrome and craniosynostosis; other Noonan syndrome genotypes have higher incidence of craniosynostosis. Sources: Literature |
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| Craniosynostosis v0.54 | MEGF8 |
Tiong Tan gene: MEGF8 was added gene: MEGF8 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: MEGF8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MEGF8 were set to 23063620 Phenotypes for gene: MEGF8 were set to Carpenter syndrome Penetrance for gene: MEGF8 were set to Complete Review for gene: MEGF8 was set to GREEN Added comment: Craniosynostosis is a key feature of Carpenter syndrome - identified in 4/4 unrelated individuals with MEGF8 biallelic variants Sources: Literature |
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| Craniosynostosis v0.52 | MASP1 |
Tiong Tan gene: MASP1 was added gene: MASP1 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: MASP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MASP1 were set to 7677137; 21258343 Phenotypes for gene: MASP1 were set to 3MC syndrome Penetrance for gene: MASP1 were set to Complete Review for gene: MASP1 was set to GREEN Added comment: Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome Sources: Literature |
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| Craniosynostosis v0.50 | PTPN11 |
Tiong Tan gene: PTPN11 was added gene: PTPN11 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PTPN11 were set to 28650561 Phenotypes for gene: PTPN11 were set to Noonan syndrome Penetrance for gene: PTPN11 were set to Complete Mode of pathogenicity for gene: PTPN11 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PTPN11 was set to GREEN Added comment: Three unrelated individuals with PTPN11-related Noonan syndrome and craniosynostosis Sources: Literature |
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| Craniosynostosis v0.48 | BRAF |
Tiong Tan gene: BRAF was added gene: BRAF was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: BRAF were set to 28650561 Phenotypes for gene: BRAF were set to CFC Penetrance for gene: BRAF were set to Complete Mode of pathogenicity for gene: BRAF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: BRAF was set to GREEN Added comment: Four unrelated individuals with CFC and craniosynostosis Sources: Literature |
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| Craniosynostosis v0.46 | KRAS |
Tiong Tan gene: KRAS was added gene: KRAS was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KRAS were set to 26249544; 28650561 Phenotypes for gene: KRAS were set to Noonan syndrome Penetrance for gene: KRAS were set to Complete Mode of pathogenicity for gene: KRAS was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: KRAS was set to GREEN Added comment: 10% of all individuals with KRAS-related Noonan syndrome have craniosynostosis Sources: Literature |
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| Craniosynostosis v0.42 | KAT6A |
Tiong Tan gene: KAT6A was added gene: KAT6A was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KAT6A were set to 30245513; 25728777 Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome Penetrance for gene: KAT6A were set to Complete Review for gene: KAT6A was set to GREEN Added comment: Low frequency association of craniosynostosis in Arboleda-Tham syndrome. Six individuals reported in two publications. Sources: Literature |
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| Craniosynostosis v0.38 | FGF10 | Tiong Tan Added comment: Comment on list classification: Two unrelated individuals in large craniosynostosis cohort with pathogenic variants in FGF10. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Craniosynostosis v0.31 | HNRNPK |
Tiong Tan gene: HNRNPK was added gene: HNRNPK was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: HNRNPK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HNRNPK were set to 26173930; 26954065; 29904177 Phenotypes for gene: HNRNPK were set to Au-Kline syndrome Penetrance for gene: HNRNPK were set to Complete Review for gene: HNRNPK was set to GREEN Added comment: Multiple unrelated individuals with Au-Kline (approx 1/3 have craniosynostosis - sagittal, metric, lambdoid) Sources: Literature |
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| Craniosynostosis v0.29 | ESCO2 |
Tiong Tan gene: ESCO2 was added gene: ESCO2 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: ESCO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESCO2 were set to 31192177 Phenotypes for gene: ESCO2 were set to 268300 ROBERTS SYNDROME Penetrance for gene: ESCO2 were set to Complete Review for gene: ESCO2 was set to AMBER Added comment: Two unrelated individuals with Roberts syndrome and craniosynostosis Sources: Literature |
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| Craniosynostosis v0.26 | DPH1 |
Tiong Tan gene: DPH1 was added gene: DPH1 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPH1 were set to 25558065; 26220823 Phenotypes for gene: DPH1 were set to 616901 DEVELOPMENTAL DELAY WITH SHORT STATURE, DYSMORPHIC FACIAL FEATURES, AND SPARSE HAIR Penetrance for gene: DPH1 were set to Complete Review for gene: DPH1 was set to AMBER Added comment: Multiple sibs from two unrelated families with DEDSSH syndrome, of which craniosynostosis was a component in some affected individuals. Sources: Literature |
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| Craniosynostosis v0.22 | COLEC11 |
Tiong Tan gene: COLEC11 was added gene: COLEC11 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: COLEC11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COLEC11 were set to 21258343 Phenotypes for gene: COLEC11 were set to 265050 3MC SYNDROME 2 Penetrance for gene: COLEC11 were set to Complete Review for gene: COLEC11 was set to GREEN Added comment: Craniosynostosis occurs in 20-30% of individuals with 3MC syndrome Sources: Literature |
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| Craniosynostosis v0.20 | CHST3 |
Tiong Tan gene: CHST3 was added gene: CHST3 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: CHST3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHST3 were set to 24300290 Phenotypes for gene: CHST3 were set to 143095 SPONDYLOEPIPHYSEAL DYSPLASIA WITH CONGENITAL JOINT DISLOCATIONS Penetrance for gene: CHST3 were set to Complete Review for gene: CHST3 was set to AMBER Added comment: Single case report of craniosynostosis in single individual with SEDCJD Sources: Literature |
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| Craniosynostosis v0.18 | B3GAT3 |
Tiong Tan gene: B3GAT3 was added gene: B3GAT3 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: B3GAT3 were set to 31438591 Phenotypes for gene: B3GAT3 were set to 245600 MULTIPLE JOINT DISLOCATIONS, SHORT STATURE, AND CRANIOFACIAL DYSMORPHISM WITH OR WITHOUT CONGENITAL HEART DEFECTS Penetrance for gene: B3GAT3 were set to Complete Review for gene: B3GAT3 was set to GREEN Added comment: Craniosynostosis is a feature of B3GAT3-related joint dislocations. Reported in multiple unrelated individuals and summarised in PMID 31438591 (2019) Sources: Literature |
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| Craniosynostosis v0.2 | SOX6 |
Seb Lunke gene: SOX6 was added gene: SOX6 was added to Craniosynostosis. Sources: Literature Mode of inheritance for gene: SOX6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SOX6 were set to 32442410 Phenotypes for gene: SOX6 were set to ADHD; Craniosynostosis; Osteochondromas Review for gene: SOX6 was set to GREEN gene: SOX6 was marked as current diagnostic Added comment: 6 LoF and 4 missense variants identified in individuals with a neurodevelopmental syndrome, however the number of families is unclear to me. Sources: Literature Sources: Literature |
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