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| Genomic newborn screening: BabyScreen+ v0.2137 | MYH7 | Zornitza Stark edited their review of gene: MYH7: Added comment: Discussed with paedric cardiologist: include bi-allelic cardiac variants as can present in the neonatal period with an aggressive cardiomyopathy and associated arrhythmias.; Changed rating: GREEN; Changed phenotypes: Cardiomyopathy, hypertrophic, 1, MIM# 192600; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.2131 | PRKG1 |
Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen. FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta). Variable age of clinical presentation. Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2. Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol. Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%). Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen. FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta). Variable age of clinical presentation. Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2. Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol. Penetrance: A study of 31 individuals with PRKG1 pathogenic variants indicated that 63% presented with an aortic dissection and 37% had aortic root enlargement. The cumulative risk of an aortic dissection or repair of an aortic aneurysm by age 55 has been estimated as 86% (95% CI: 70-95%). Discussed with a paediatric cardiologist: variable penetrance and age of onset, does not fulfil criteria for gNBS. Sources: ClinGen |
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| Genomic newborn screening: BabyScreen+ v0.2129 | LOX |
Zornitza Stark changed review comment from: Assessed as 'strong actionability' in paediatric patients by ClinGen. FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta). Variable age of clinical presentation. Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2. Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol. Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection. Sources: ClinGen; to: Assessed as 'strong actionability' in paediatric patients by ClinGen. FTAAD is a rare genetic vascular disease characterized by the familial occurrence of thoracic aortic aneurysm, dissection, or dilatation affecting one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta). Variable age of clinical presentation. Prophylactic surgical repair of the aorta is recommended at 4.5-5.0 cm for patients with pathogenic variants in MYH11, SMAD3, and ACTA2 and at 4.0-4.5 cm for patients with pathogenic variants in TGFBR1 or TGFBR2. Beta adrenergic-blocking agents are recommended to reduce aortic dilation. Losartan was added as an alternative to beta adrenergic-blocking agents in FTAAD after studies showed its efficacy in children and young adults with MFS who were randomly assigned to losartan or atenolol. Penetrance: A study of 15 individuals with LOX pathogenic variants indicated that 73% had aortic aneurysms and 1 individual (7%) had an aortic dissection. Discussed with paediatric cardiologist: variable penetrance and age of onset, does not fit with criteria for gNBS. Sources: ClinGen |
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| Genomic newborn screening: BabyScreen+ v0.2128 | JUP |
Zornitza Stark changed review comment from: Screen for bi-allelic disease as can be earlier onset, more severe.; to: Discussed potentially just screening for bi-allelic disease as can be earlier onset, more severe. Discussed further with a paediatric cardiologist: variable age of onset and penetrance, therefore does not meet criteria. |
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| Genomic newborn screening: BabyScreen+ v0.2127 | DSP |
Zornitza Stark changed review comment from: Screen for bi-allelic disease as can be more severe, earlier onset.; to: Discussed screening for bi-allelic disease as can be more severe, earlier onset. Also discussed with paediatric cardiologist: variable age of onset and penetrance, exclude. |
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| Genomic newborn screening: BabyScreen+ v0.1982 | TOP2B |
Lilian Downie gene: TOP2B was added gene: TOP2B was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: TOP2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TOP2B were set to PMID: 31409799, PMID: 35063500, PMID: 32128574, PMID: 33459963 Phenotypes for gene: TOP2B were set to B-cell immunodeficiency, distal limb anomalies, and urogenital malformations MIM#609296 Review for gene: TOP2B was set to AMBER Added comment: congenital onset humoral immunodeficiency with undetectable B cells, distal limb anomalies, dysmorphic facial features, and urogenital malformations Treatment immunoglobulin (only partially treats phenotype) no literature for evidence around immunoglobulin treatment. Suggest RED but maybe discuss with immunologist? Sources: Expert list |
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| Genomic newborn screening: BabyScreen+ v0.1872 | HMGCS2 |
Lilian Downie gene: HMGCS2 was added gene: HMGCS2 was added to gNBS. Sources: Expert list Mode of inheritance for gene: HMGCS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMGCS2 were set to PMID: 32259399, 32470406 Phenotypes for gene: HMGCS2 were set to HMG-CoA synthase-2 deficiency MIM#605911 Penetrance for gene: HMGCS2 were set to Incomplete Review for gene: HMGCS2 was set to AMBER Added comment: Metabolic disorder; patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. Recover completely between illnesses, do develop fatty liver. ?incomplete penetrance or variable age of onset On GUARDIAN and Rx Genes Rx IV glucose during acute episodes, avoid prolonged fasting Metabolic parameters are normal in between episodes, so no ability to do a confirmatory biochemical test. Pros: readily treatable if child has an episode Cons: unncessary worry as child may never have episode Super rare ?30 cases Discuss with JC? Sources: Expert list |
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| Genomic newborn screening: BabyScreen+ v0.1425 | DMD |
Zornitza Stark changed review comment from: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only. Onset in early childhood. Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping. Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels. For review.; to: Well established gene-disease association. Milder phenotypes such as BMD and DCM are also associated with variants in this gene. Females typically at risk for cardiac disease only. Onset in early childhood. Treatment: Eteplirsen, Casimersen and Golodirsen for exon skipping 51, 45 and 53, respectively. Vitolarsen has also been approved for exon 53 skipping. Pilots are underway to assess NBS for DMD, including one planned in NSW. Most programs are based on raised CK levels. For review. Discuss with neurology. Should we only report variants that are likely to benefit from treatment? |
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| Genomic newborn screening: BabyScreen+ v0.1151 | COL11A1 |
Zornitza Stark changed review comment from: Mono-allelic variants in this gene cause Stickler syndrome, as well as isolated post-lingual deafness, and the rare Marshall syndrome. There is some genotype-phenotype correlation. Treatment: ocular surveillance and surgery to prevent retinal detachment For review; to: Mono-allelic variants in this gene cause Stickler syndrome, as well as isolated post-lingual deafness, and the rare Marshall syndrome. There is some genotype-phenotype correlation. Treatment: ocular surveillance and surgery to prevent retinal detachment. Usually after age 2-3 years. Discussed with ophthalmology: would start glaucoma surveillance in first year of life. |
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| Genomic newborn screening: BabyScreen+ v0.1151 | COL2A1 |
Zornitza Stark changed review comment from: Variants in this gene are associated with a range of skeletal phenotypes. Onset and severity can be variable. Treatment: surveillance and prophylactic retinal laser treatment to prevent retinal detachment. For review.; to: Variants in this gene are associated with a range of skeletal phenotypes. Onset and severity can be variable. Treatment: surveillance and prophylactic retinal laser treatment to prevent retinal detachment. This is usually after the age of 2-3 years. Discussed with ophthalmology, would start glaucoma surveillance in the first year of life. |
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| Genomic newborn screening: BabyScreen+ v0.1051 | ERCC5 |
Zornitza Stark changed review comment from: Bi-allelic variants cause a range of DNA repair disorders. Variable severity and age of onset of manifestations. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. For discussion.; to: Bi-allelic variants cause a range of DNA repair disorders. Variable severity and age of onset of manifestations. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. |
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| Genomic newborn screening: BabyScreen+ v0.1047 | ERCC2 |
Zornitza Stark changed review comment from: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE. DNA repair disorder. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. For discussion.; to: Bi-allelic variants in this gene cause a range of conditions, including COFS, trichothiodystrophy and XPE. DNA repair disorder. Some features are treatable: avoid exposure to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources). Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil. |
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| Genomic newborn screening: BabyScreen+ v0.728 | ADAR | Zornitza Stark commented on gene: ADAR: To be discussed further with neurology. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.661 | FLAD1 |
Zornitza Stark changed review comment from: Well established gene-disease association, more than 10 families reported. The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment. For discussion. Included as a treatable disorder in rx-genes. Confirmatory non-genetic testing: Plasma acylcarnitine profile, Urine organic acid analysis,; to: Well established gene-disease association, more than 10 families reported. The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment. Included as a treatable disorder in rx-genes. Confirmatory non-genetic testing: Plasma acylcarnitine profile, Urine organic acid analysis, |
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| Genomic newborn screening: BabyScreen+ v0.587 | CYP11A1 |
Zornitza Stark changed review comment from: Well established gene-disease association. Congenital onset. For review: should we include mono-allelic variants?; to: Well established gene-disease association. Congenital onset. Mono-allelic variants discussed: a single family reported only. Does not meet criteria for inclusion. MOI set to bi-allelic. |
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| Genomic newborn screening: BabyScreen+ v0.585 | ATP7B | Zornitza Stark commented on gene: ATP7B: Group discussion: acute liver failure can be fatal, and the disorder is treatable. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: BabyScreen+ v0.0 | ISCU |
Zornitza Stark gene: ISCU was added gene: ISCU was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: ISCU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ISCU were set to Myopathy with defiency of succinate dehydrogenase |
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