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Fetal anomalies v7.22 NPR2 Ida Ertmanska changed review comment from: PMID: 40424589 Renes et al., 2025
Report of 18 different NPR2 variants in 27 Dutch children with short stature (all heterozygous). Truncating variants (5/18) had a more severe effect than non-truncating variants (-3.3 vs -2.5 SDS respectively). Also, variants in the kinase homology domain (6/18 variants) were more severe than variants in other domains (-3.2 SDS vs -2.5 SDS). Majority of patients had mild features suggestive of skeletal dysplasia: mild dysproportion, cone-shaped epiphysis, and shortened metacarpals. 21/27 individuals had dysmorphic features of the hands, 13/27 with brachydactyly, clinodactyly and syndactyly also reported. All the children were 4-18 years old at the start of GH treatment (and height measurement).

Consider MOI change to BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as heterozygous individuals also present with skeletal features, limb disorders.; to: PMID: 40424589 Renes et al., 2025
Report of 18 different NPR2 variants in 27 Dutch children with short stature (all heterozygous). Truncating variants (5/18) had a more severe effect than non-truncating variants (-3.3 vs -2.5 SDS respectively). Also, variants in the kinase homology domain (6/18 variants) were more severe than variants in other domains (-3.2 SDS vs -2.5 SDS). Majority of patients had mild features suggestive of skeletal dysplasia: mild dysproportion, cone-shaped epiphysis, and shortened metacarpals. 21/27 individuals had dysmorphic features of the hands, 13/27 with brachydactyly, clinodactyly and syndactyly also reported. All the children were 4-18 years old at the start of GH treatment (and height measurement).

Brachydactyly is a consistent feature in recessive NPR2-related skeletal dysplasia (Acromesomelic dysplasia 1, Maroteaux type). Heterozygous individuals also present with skeletal features, limb disorders. Hence, consider MOI change to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Fetal anomalies v7.22 NPR2 Ida Ertmanska changed review comment from: PMID: 40424589 Renes et al., 2025
Report of 18 different NPR2 variants in 27 Dutch children with short stature (all heterozygous). Truncating variants (5/18) had a more severe effect than non-truncating variants (-3.3 vs -2.5 SDS respectively). Also, variants in the kinase homology domain (6/18 variants) were more severe than variants in other domains (-3.2 SDS vs -2.5 SDS). Majority of patients had mild features suggestive of skeletal dysplasia: mild dysproportion, cone-shaped epiphysis, and shortened metacarpals. 21/27 individuals had dysmorphic features of the hands, 13/27 with brachydactyly, clinodactyly and syndactyly also reported. All the children were 4-18 years old at the start of GH treatment (and height measurement) so the TD criteria are fulfilled for at least 5 individuals (> 2 years old and height <-3SD).

Consider MOI change to BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as heterozygous individuals also present with skeletal features, limb disorders.; to: PMID: 40424589 Renes et al., 2025
Report of 18 different NPR2 variants in 27 Dutch children with short stature (all heterozygous). Truncating variants (5/18) had a more severe effect than non-truncating variants (-3.3 vs -2.5 SDS respectively). Also, variants in the kinase homology domain (6/18 variants) were more severe than variants in other domains (-3.2 SDS vs -2.5 SDS). Majority of patients had mild features suggestive of skeletal dysplasia: mild dysproportion, cone-shaped epiphysis, and shortened metacarpals. 21/27 individuals had dysmorphic features of the hands, 13/27 with brachydactyly, clinodactyly and syndactyly also reported. All the children were 4-18 years old at the start of GH treatment (and height measurement).

Consider MOI change to BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as heterozygous individuals also present with skeletal features, limb disorders.
Fetal anomalies v7.11 NPR2 Ida Ertmanska changed review comment from: PMID: 40424589 Renes et al., 2025
Report of 18 different NPR2 variants in 27 Dutch children with short stature (all heterozygous). Truncating variants (5/18) had a more severe effect than non-truncating variants (-3.3 vs -2.5 SDS respectively). Also, variants in the kinase homology domain (6/18 variants) were more severe than variants in other domains (-3.2 SDS vs -2.5 SDS). Majority of patients had mild features suggestive of skeletal dysplasia. 21/27 individuals had dysmorphic features of the hands, 13/27 with brachydactyly, clinodactyly and syndactyly also reported. All the children were 4-18 years old at the start of GH treatment (and height measurement) so the TD criteria are fulfilled for at least 5 individuals (> 2 years old and height <-3SD).; to: PMID: 40424589 Renes et al., 2025
Report of 18 different NPR2 variants in 27 Dutch children with short stature (all heterozygous). Truncating variants (5/18) had a more severe effect than non-truncating variants (-3.3 vs -2.5 SDS respectively). Also, variants in the kinase homology domain (6/18 variants) were more severe than variants in other domains (-3.2 SDS vs -2.5 SDS). Majority of patients had mild features suggestive of skeletal dysplasia: mild dysproportion, cone-shaped epiphysis, and shortened metacarpals. 21/27 individuals had dysmorphic features of the hands, 13/27 with brachydactyly, clinodactyly and syndactyly also reported. All the children were 4-18 years old at the start of GH treatment (and height measurement) so the TD criteria are fulfilled for at least 5 individuals (> 2 years old and height <-3SD).

Consider MOI change to BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as heterozygous individuals also present with skeletal features, limb disorders.
Fetal anomalies v1.983 GATM Arina Puzriakova Phenotypes for gene: GATM were changed from ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY to Cerebral creatine deficiency syndrome 3, OMIM:612718
Fetal anomalies v1.103 USP18 Arina Puzriakova commented on gene: USP18: Added 'treatable' tag as clinical remission was achieved in a patient following rapid genetic diagnosis and subsequent treatment with the JAK inhibitor ruxolitinib
Fetal anomalies v0.166 OTULIN Rebecca Foulger edited their review of gene: OTULIN: Added comment: This gene and phenotype were discussed during review of borderline cases in April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Lipodystrophy. Early treatment could be helpful but no obvious detectable prenatal phenotype. Action taken: Demoted gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.135 GATM Rebecca Foulger Source Expert Review Red was added to GATM.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.135 ATM Rebecca Foulger Source Expert Review Red was added to ATM.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v0.134 GATM Rebecca Foulger edited their review of gene: GATM: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted GATM gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.134 ATM Rebecca Foulger edited their review of gene: ATM: Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted ATM gene rating from Green to Red.; Changed rating: RED
Fetal anomalies v0.9 GATM Rebecca Foulger reviewed gene: GATM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.9 ATM Rebecca Foulger reviewed gene: ATM: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.1 GATM Rebecca Foulger gene: GATM was added
gene: GATM was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GATM were set to ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY
Fetal anomalies v0.1 ATM Rebecca Foulger gene: ATM was added
gene: ATM was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ATM were set to ATAXIA-TELANGIECTASIA