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| BabyScreen+ newborn screening v1.114 | TBCE | Tommy Li Added phenotypes Hypoparathyroidism retardation dysmorphism syndrome for gene: TBCE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | SMO | Tommy Li Added phenotypes Medulloblastoma for gene: SMO | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | DHCR24 | Tommy Li Added phenotypes Desmosterolosis for gene: DHCR24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | CTDP1 | Tommy Li Added phenotypes Congenital cataracts - facial dysmorphism - neuropathy for gene: CTDP1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | B3GAT3 | Tommy Li Added phenotypes Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects for gene: B3GAT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | ATP1A2 | Tommy Li Added phenotypes Developmental and epileptic encephalopathy 98, MIM# 619605; Alternating hemiplegia of childhood 1, MIM#104290; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602 for gene: ATP1A2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.2063 | SMARCD2 |
Lilian Downie gene: SMARCD2 was added gene: SMARCD2 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: SMARCD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMARCD2 were set to PubMed: 28369036, 33279574, 33025377 Phenotypes for gene: SMARCD2 were set to Specific granule deficiency 2 MIM#617475 Review for gene: SMARCD2 was set to GREEN Added comment: recurrent infections due to defective neutrophil development. Bone marrow findings include paucity of neutrophil granulocytes, absence of granule proteins in neutrophils, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and patients may die in early childhood unless they undergo hematopoietic stem cell transplantation. Most patients have additional findings, including delayed development, mild dysmorphic features, tooth abnormalities, and distal skeletal defects Rx bone marrow transplant Sources: Expert list |
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| BabyScreen+ newborn screening v0.2052 | TMEM165 |
Lilian Downie gene: TMEM165 was added gene: TMEM165 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: TMEM165 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM165 were set to PMID: 28323990, PMID: 35693943, PMID: 22683087 Phenotypes for gene: TMEM165 were set to Congenital disorder of glycosylation, type IIk MIM#614727 Review for gene: TMEM165 was set to AMBER Added comment: Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern Rx D-galactose (single paper, 2 unrelated patients and an in vitro study) ?inadequete evidence for treatment? Might need to check with JC if we would offer it maybe include Sources: Expert list |
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| BabyScreen+ newborn screening 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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| BabyScreen+ newborn screening v0.1973 | HELLS |
Zornitza Stark gene: HELLS was added gene: HELLS was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: HELLS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HELLS were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 4, MIM# 616911 Review for gene: HELLS was set to GREEN Added comment: Congenital onset. Immunodeficiency-centromeric instability-facial anomalies syndrome-4 is characterized by recurrent infections in childhood and variable dysmorphic facial features. Laboratory studies show hypomethylation of certain chromosomal regions. Additional features, including delayed development, are variable. At least 4 unrelated families reported. Treatment: bone marrow transplant. Sources: Expert list |
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| BabyScreen+ newborn screening v0.1772 | RUNX1 |
Zornitza Stark gene: RUNX1 was added gene: RUNX1 was added to gNBS. Sources: ClinGen for review, treatable, haematological tags were added to gene: RUNX1. Mode of inheritance for gene: RUNX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: RUNX1 were set to Platelet disorder, familial, with associated myeloid malignancy, MIM# 601399 Review for gene: RUNX1 was set to AMBER Added comment: Assessed as 'moderate actionability' in paediatric patients by ClinGen. HTHCPS is characterized by mild to moderate thrombocytopenia with normal platelet size, abnormal platelet functioning (defective release of delta granules and/or aggregation defects), and an increased risk of developing a haematologic malignancy. Age of onset of bleeding can be highly variable, with some individuals presenting in early infancy and others not recognizing their symptoms until much later in life. Severe thrombocytopenia or profound platelet dysfunction can result in recognition during the perinatal or infancy period. Hematologic malignancies can occur in childhood or adulthood; the range of age of onset is wide with a median age of 33 years. Use of clotting promotors (e.g., desmopressin, epsilon aminocaproic acid, tranexamic acid) can be used for surgeries, injuries, or dental treatments. Platelet transfusions may be used for severe bleeding or procedures with a high bleeding risk. Though there is no specific treatment for HTHCPS, there are recommendations regarding the indications and timing of hematopoietic stem cell transplantation (HSCT) that vary. HSCT in pre-malignancy patients, particularly in the absence of any clonal progression, is debatable due to transplantation-associated risks and incomplete penetrance. Some suggested indications for HSCT include severe or symptomatic cytopenias, severe marrow dysplasia (particularly in the context of falling blood counts), complex or high-risk (e.g., monosomy 7) cytogenetic abnormalities (particularly if the clones are large or increasing in size) and increasing blasts >5%. Consider use of a medical alert bracelet for thrombocytopenia, platelet dysfunction, or hematologic malignancy as indicated. Sources: ClinGen |
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| BabyScreen+ newborn screening v0.1724 | ITGB3 |
Zornitza Stark gene: ITGB3 was added gene: ITGB3 was added to gNBS. Sources: ClinGen treatable, haematological tags were added to gene: ITGB3. Mode of inheritance for gene: ITGB3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ITGB3 were set to Glanzmann thrombasthenia 2, MIM# 619267 Review for gene: ITGB3 was set to GREEN Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen. GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long. Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness. The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies. Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting. Sources: ClinGen |
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| BabyScreen+ newborn screening v0.1722 | ITGA2B |
Zornitza Stark gene: ITGA2B was added gene: ITGA2B was added to gNBS. Sources: ClinGen treatable, haematological tags were added to gene: ITGA2B. Mode of inheritance for gene: ITGA2B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ITGA2B were set to Glanzmann thrombasthaenia 1, MIM# 273800 Review for gene: ITGA2B was set to GREEN Added comment: Rated as 'strong actionability' in paediatric patients by ClinGen. GT can present soon after birth with episodic mucocutaneous bleeding, purpura, petechiae, unprovoked bruising, and excessive bleeding from the umbilical stump or post-circumcision. Major bleeding complications during the neonatal period, such as ICH following delivery are rare. The clinical severity of GT tends to diminish with age, although the bleeding manifestations persist and are life-long. Recombinant activated factor VII (rFVIIa) may be considered for patients with: moderate to severe acute bleeding; for treatment of refractory minor bleeds; for prophylaxis in patients with frequent severe bleeds; treatment during minor and major surgery; and in patients who are refractory to platelet transfusion. Some guidelines suggest utilizing rFVIIa as a first line therapy and saving platelet transfusion for more severe or non-responsive bleeds. High doses have been successful, particularly if used early and upfront. rFVIIa in a dose of =80 µg/kg at intervals of 2.5 h or less were observed to be safe and effective in nonsurgical bleeds, minor and major procedures in patients with or without antibodies, and/or refractoriness. The International Glanzmann Thrombasthenia Registry (GTR), published in 2015, studied 184 patients with 829 bleeding episodes and 96 patients with 206 surgical interventions. rFVIIa alone was used in 124/829 bleeds and the proportion of successful treatment to stop bleeding was 91%. In patients without antibodies/refractoriness, rFVIIa, either alone or with antifibrinolytics, and platelets±antifibrinolytics were rated 100% effective for 24 minor and 4 major procedures. The lowest effectiveness of rFVIIa treatment alone was 88.9% (16/18 effective minor procedures) in refractory patients with platelet antibodies. Desmopressin (DDAVP) may be considered as an additional treatment for mild bleeding episodes. DDAVP has been shown to be effective in many bleeding disorders, including inherited platelet function disorders. However, DDAVP efficacy among GT patients has not been established and guideline recommendations are conflicting. Sources: ClinGen |
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| BabyScreen+ newborn screening v0.1272 | PIGA | John Christodoulou reviewed gene: PIGA: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 32256299, PMID: 24706016, PMID: 25885527, PMID: 24259184; Phenotypes: hypotonia, infantile epileptic encephalopathy, facial dysmorphism; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1154 | GUSB | John Christodoulou reviewed gene: GUSB: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31661765, PMID: 32063397; Phenotypes: facial dysmorphisms, skeletal deformities, cardiac valve involvement, ocular involvement, motor delay, developmental delay, ID; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.662 | LDLR |
Zornitza Stark changed review comment from: ClinGen: 'strong actionability' in paediatric patients. For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood. Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.; to: ClinGen: 'strong actionability' in paediatric patients. For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood. Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment. Include bi-allelic disease in gNBS. Continue considering if and when mono-allelic disease should be included. |
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| BabyScreen+ newborn screening v0.523 | D2HGDH | John Christodoulou reviewed gene: D2HGDH: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: developmental delay, dysmorphism, epileptic encephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.222 | LDLR |
Zornitza Stark changed review comment from: ClinGen: 'strong actionability' in paediatric patients. For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment.; to: ClinGen: 'strong actionability' in paediatric patients. For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood. Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment. |
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| BabyScreen+ newborn screening v0.177 | ATP1A2 | Zornitza Stark Phenotypes for gene: ATP1A2 were changed from Hemiplegic migraine to Alternating hemiplegia of childhood 1, MIM#104290; Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602; Developmental and epileptic encephalopathy 98, MIM# 619605 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.173 | ATP1A2 | Zornitza Stark reviewed gene: ATP1A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alternating hemiplegia of childhood 1, MIM#104290, Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies, MIM# 619602, Developmental and epileptic encephalopathy 98, MIM# 619605; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.0 | TBCE |
Zornitza Stark gene: TBCE was added gene: TBCE was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TBCE were set to Hypoparathyroidism retardation dysmorphism syndrome |
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| BabyScreen+ newborn screening v0.0 | SMO |
Zornitza Stark gene: SMO was added gene: SMO was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: SMO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SMO were set to Medulloblastoma |
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| BabyScreen+ newborn screening v0.0 | DHCR24 |
Zornitza Stark gene: DHCR24 was added gene: DHCR24 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: DHCR24 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DHCR24 were set to Desmosterolosis |
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| BabyScreen+ newborn screening v0.0 | CTDP1 |
Zornitza Stark gene: CTDP1 was added gene: CTDP1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: CTDP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CTDP1 were set to Congenital cataracts - facial dysmorphism - neuropathy |
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| BabyScreen+ newborn screening v0.0 | B3GAT3 |
Zornitza Stark gene: B3GAT3 was added gene: B3GAT3 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: B3GAT3 were set to Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects |
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