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BabyScreen+ newborn screening

Gene: RET

Green List (high evidence)

RET (ret proto-oncogene)
EnsemblGeneIds (GRCh38): ENSG00000165731
EnsemblGeneIds (GRCh37): ENSG00000165731
OMIM: 164761, Gene2Phenotype
RET is in 23 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Established gene-disease associations.

Assessed as 'strong actionability' in paediatric patients by ClinGen.

Onset of MEN2A is typically prior to age 35, usually between ages 5 and 25. MTC is generally the first manifestation in MEN2A with probands presenting with a neck mass or neck pain. Metastatic spread is common. MTC is the most common cause of death in patients with MEN2A.

PHEOs usually present after MTC or concomitantly but are the first manifestation in 13-27% of individuals; they occur in about 50% of individuals. PHEOs are diagnosed at an earlier age, have subtler symptoms, and are more likely to be bilateral than sporadic tumors, with malignant transformation occurring in about 4% of cases. Even without malignant progression, PHEOs can be lethal from intractable hypertension or anesthesia-induced hypertensive crises. Depending on the risk category of the RET pathogenic variant, PHEOs have been observed as early as 5 years of age.

For MEN2A children with a “high-risk” pathogenic variant, patients should undergo annual ultrasound and screening for increased calcitonin levels starting at 3 years of age and proceed to thyroidectomy when elevated levels are detected or at 5 years of age. For patients with a “moderate-risk” pathogenic variant, considering the clinical variability of disease expression in family members in this category, annual physical examination, cervical US, and measurement of serum calcitonin levels, should begin at 5 years of age.

Biochemical surveillance for PHPT should begin at 11 years and 16 years of age for patients with high- and moderate-risk variants, respectively; this screening is recommended annually for “high-risk” patients and at least every 2-3 years in “moderate-risk” patients.

Biochemical screening for PHEO should begin at age 11 for patients with high-risk variants and age 16 for patients with moderate-risk variants.

For review: some actionability in first 5 years, variants can be stratified in terms of risk.
Created: 14 Dec 2022, 7:52 a.m. | Last Modified: 17 Jan 2023, 2:24 a.m.
Panel Version: 0.1821

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Multiple endocrine neoplasia IIA, MIM# 171400; Multiple endocrine neoplasia IIB, MIM# 162300

History Filter Activity

17 Jan 2023, Gel status: 3

Removed Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag for review was removed from gene: RET.

29 Dec 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: ret has been classified as Green List (High Evidence).

14 Dec 2022, Gel status: 3

Added Tag, Added Tag, Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag for review tag was added to gene: RET. Tag cancer tag was added to gene: RET. Tag treatable tag was added to gene: RET.

18 Sep 2022, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: RET was added gene: RET was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: RET were set to Multiple endocrine neoplasia IIB; Multiple endocrine neoplasia IIA