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| BabyScreen+ newborn screening v1.114 | MLH1 | Tommy Li Added phenotypes Mismatch repair cancer syndrome 1, MIM# 276300 for gene: MLH1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.1 | MLH1 | Zornitza Stark Tag for review was removed from gene: MLH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1829 | MLH1 | Zornitza Stark Classified gene: MLH1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1829 | MLH1 | Zornitza Stark Gene: mlh1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1828 | MLH1 | Zornitza Stark edited their review of gene: MLH1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1801 | MLH1 |
Zornitza Stark changed review comment from: Note mono-allelic variants are associated with adult-onset cancer risk. MMRCS rated as 'strong actionability' in paediatric patients by ClinGen. The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years. The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested: •Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended. •Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age. •Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years. •Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician. •For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years. •Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years. •To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI. Estimated penetrance in MMRCS: •50% develop small-bowel adenomas •>90% develop colorectal adenomas •59 to 70% develop colorectal cancer •58 to 70% develop high-grade brain tumours •20-40% develop lymphoma •10-40% develop leukemia •10 to 18% develop small-bowel cancer •<10% develop endometrial cancer •<10% develop urinary tract cancer •<10% develop cancer of other sites; to: Note mono-allelic variants are associated with adult-onset cancer risk. MMRCS rated as 'strong actionability' in paediatric patients by ClinGen. The hallmark of MMRCS is early onset cancer, most often in childhood or young adulthood. The median age of onset of the first tumor is 7.5 years, with a wide range observed (0.4-39 years). A large portion (up to 40%) of patients develop metachronous second malignancies. The median survival after diagnosis of the primary tumor is less than 30 months. Prognosis depends on the possibility of complete resection, making early detection paramount. It is unclear what tumor spectrum will emerge among adults with MMRCS. Brain tumors are frequent and often diagnosed in the first decade of life. The rate of progression appears to be rapid in the brain tumors. The median age at diagnosis of brain tumors is 9 years (range, 2-40 years). Brain tumors are by far the most common cause of death. Colonic adenomatous oligopolyposis typically is diagnosed between 5 and 10 years of age. The progression of adenomas to malignancy in MMRCS is the most rapid of any inherited colorectal cancer syndrome. Among MMRCS patients presenting with colorectal cancer (CRC), the median age at diagnosis was 16 years (range, 8-48 years) with more than half of patients classified as pediatric-onset CRC. The age of onset of small-bowel adenomas is later; they typically develop in the second decade of life. The median age at diagnosis of small-bowel cancer was 28 years, with a range of 11-42 years. The lifetime risk of gastrointestinal cancer among MMRCS patients is the highest reported of all gastrointestinal cancer predisposition syndromes as a function of age. The median age at diagnosis of hematologic malignancy is 6.6 years. Endometrial cancer has been diagnosed between 19 and 44 years. The age at diagnosis of urinary tract tumors has ranged from 10 to 22 years. The management of MMRCS is based on the current estimates of neoplasia risk and the early age of onset for the cancers, which have led to tentative guidelines for the management of these patients. The age at which to begin surveillance varies by guideline and is represented below as age ranges. In patients with MMRCS, the following surveillance is suggested: •Screening for CRC by colonoscopy is recommended annually beginning at age 6 to 8 years. Once polyps are identified, colonoscopy every 6 months is recommended. •Annual surveillance for small-bowel cancer by upper endoscopy and video capsule endoscopy is suggested beginning at 8 to 10 years of age. Monitoring of hemoglobin levels every 6 months also is suggested, beginning at 8 years of age. •Surveillance for brain tumors by brain MRI every 6 to 12 months is suggested starting at the time of diagnosis even in the first year of life to age 2 years. •Currently, no proven surveillance modalities for leukemia or lymphoma have been identified. Complete blood count to screen for leukemia is suggested every 6 months beginning at 1 year of age. Clinical examinations and abdominal ultrasounds to screen for lymphoma every 6 months may be considered by the treating physician. •For individuals with a uterus, surveillance for endometrial cancer is suggested by transvaginal ultrasound, pelvic examination, and endometrial sampling annually starting at age 20 years. •Surveillance for cancer of the urinary tract is suggested, with annual urinalysis starting at age 10 to 20 years. •To screen for other types of tumors, whole-body MRI could be considered once a year starting at 6 years of age or when anesthesia is not needed. This method should not replace the need for ultrasound and brain MRI. Estimated penetrance in MMRCS: •50% develop small-bowel adenomas •>90% develop colorectal adenomas •59 to 70% develop colorectal cancer •58 to 70% develop high-grade brain tumours •20-40% develop lymphoma •10-40% develop leukemia •10 to 18% develop small-bowel cancer •<10% develop endometrial cancer •<10% develop urinary tract cancer •<10% develop cancer of other sites |
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| BabyScreen+ newborn screening v0.1801 | MLH1 | Zornitza Stark Marked gene: MLH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1801 | MLH1 | Zornitza Stark Gene: mlh1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1801 | MLH1 | Zornitza Stark Phenotypes for gene: MLH1 were changed from Lynch syndrome to Mismatch repair cancer syndrome 1, MIM# 276300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1800 | MLH1 | Zornitza Stark Mode of inheritance for gene: MLH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1796 | MLH1 | Zornitza Stark Classified gene: MLH1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1796 | MLH1 | Zornitza Stark Gene: mlh1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1793 | MLH1 |
Zornitza Stark Tag for review tag was added to gene: MLH1. Tag cancer tag was added to gene: MLH1. Tag treatable tag was added to gene: MLH1. |
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| BabyScreen+ newborn screening v0.1793 | MLH1 | Zornitza Stark reviewed gene: MLH1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mismatch repair cancer syndrome 1, MIM# 276300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.0 | MLH1 |
Zornitza Stark gene: MLH1 was added gene: MLH1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: MLH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: MLH1 were set to Lynch syndrome |
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