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Severe microcephaly v9.28 DNA2 Ida Ertmanska changed review comment from: ROTHMUND-THOMSON SYNDROME:
PMID: 37055165 Di Lazzaro Filho et al., 2023
OMIM 620819 summary: Study reported 8 children from 7 families with Rothmund-Thomson syndrome and mutation in the DNA2 gene. 6 of the children were Brazilian and 2 were sibs of Swiss/Portuguese ancestry. Clinical findings included severe growth failure, with some individuals showing signs suggestive of growth hormone or combined pituitary hormone deficiency; widespread poikiloderma; cutaneous photosensitivity and bullae; sparse hair, eyebrows, and eyelashes; dystrophic nails; congenital cataracts and other ocular anomalies, including glaucoma, microphthalmia, and corneal opacities, with Peters anomaly and optic atrophy in 1 patient each; craniofacial dysmorphisms, including severe microcephaly; and skeletal anomalies, including osteopenia, platyspondyly, flared and/or irregular metaphyses, and short metacarpals and phalanges.

6/6 patients above age 2 years had short stature of more than 2 SDS below mean (-4.3 to -8.1SDS). Microcephaly was not severe at birth: between -0.3 to -2.3SDS, but progressed in all patients and was more than -3SDS in unrelated patients.
All 7 probands harboured a recurrent DNA2: c.588–2214A>G intronic variant, in addition to other DNA2 variants in trans: 5 individuals had intragenic exon deletions, one harboured missense variant c.143T>C, p.Leu48Pro (not reported in gnomaD), and sibs in Family 7 had a frameshift variant.

PMID: 40693833 Ay et al., 2025
Report of a female Turkish proband with Rothmund-Thomson syndrome and comp het DNA2 variants: deep intronic c.588-2214A>G and missense c.2519 T>C, Leu840Pro (not in gnomAD v4). She presented with hallmark features of the syndrome: short stature, poikiloderma, corneal dystrophy, bilateral cataracts, skin photosensitivity and blistering, hand contractures, dystrophic nails. Parents are non-consanguineous. Microcephaly not reported; her height was 76cm (-6.3SDS) at 4 yo.; to: ROTHMUND-THOMSON SYNDROME:
PMID: 37055165 Di Lazzaro Filho et al., 2023
OMIM 620819 summary: Study reported 8 children from 7 families with Rothmund-Thomson syndrome and mutation in the DNA2 gene. 6 of the children were Brazilian and 2 were sibs of Swiss/Portuguese ancestry. Clinical findings included severe growth failure, with some individuals showing signs suggestive of growth hormone or combined pituitary hormone deficiency; widespread poikiloderma; cutaneous photosensitivity and bullae; sparse hair, eyebrows, and eyelashes; dystrophic nails; congenital cataracts and other ocular anomalies, including glaucoma, microphthalmia, and corneal opacities, with Peters anomaly and optic atrophy in 1 patient each; craniofacial dysmorphisms, including severe microcephaly; and skeletal anomalies, including osteopenia, platyspondyly, flared and/or irregular metaphyses, and short metacarpals and phalanges.

6/6 patients above age 2 years had short stature of more than 2 SDS below mean (-4.3 to -8.1SDS). Microcephaly was not severe at birth: between -0.3 to -2.3SDS, but progressed in all patients and was more than -3SDS in unrelated patients.
All 7 probands harboured a recurrent DNA2: c.588–2214A>G intronic variant, in addition to other DNA2 variants in trans: 5 individuals had intragenic exon deletions, one harboured missense variant c.143T>C, p.Leu48Pro (not reported in gnomaD), and sibs in Family 7 had a frameshift variant.

PMID: 40693833 Ay et al., 2025
Report of a female Turkish proband with Rothmund-Thomson syndrome and comp het DNA2 variants: deep intronic c.588-2214A>G and missense c.2519 T>C, Leu840Pro (not in gnomAD v4). She presented with hallmark features of the syndrome: short stature, poikiloderma, corneal dystrophy, bilateral cataracts, skin photosensitivity and blistering, hand contractures, dystrophic nails. Parents are non-consanguineous. Microcephaly not reported; her height was 76cm (-6.3SDS) at 4 yo.

This gene is associated with AR Rothmund-Thomson syndrome, type 4, OMIM:620819 in OMIM as of 11th Sept 2026.
Severe microcephaly v9.28 DNA2 Ida Ertmanska edited their review of gene: DNA2: Changed publications to: 37055165, 40693833
Severe microcephaly v9.28 DNA2 Ida Ertmanska changed review comment from: PMID: 37055165 Di Lazzaro Filho et al., 2023
Summary from OMIM 620819: Study reported 8 children from 7 families with Rothmund-Thomson syndrome and mutation in the DNA2 gene. 6 of the children were Brazilian and 2 were sibs of Swiss/Portuguese ancestry. Clinical findings included severe growth failure, with some individuals showing signs suggestive of growth hormone or combined pituitary hormone deficiency; widespread poikiloderma; cutaneous photosensitivity and bullae; sparse hair, eyebrows, and eyelashes; dystrophic nails; congenital cataracts and other ocular anomalies, including glaucoma, microphthalmia, and corneal opacities, with Peters anomaly and optic atrophy in 1 patient each; craniofacial dysmorphisms, including severe microcephaly; and skeletal anomalies, including osteopenia, platyspondyly, flared and/or irregular metaphyses, and short metacarpals and phalanges.; to: ROTHMUND-THOMSON SYNDROME:
PMID: 37055165 Di Lazzaro Filho et al., 2023
OMIM 620819 summary: Study reported 8 children from 7 families with Rothmund-Thomson syndrome and mutation in the DNA2 gene. 6 of the children were Brazilian and 2 were sibs of Swiss/Portuguese ancestry. Clinical findings included severe growth failure, with some individuals showing signs suggestive of growth hormone or combined pituitary hormone deficiency; widespread poikiloderma; cutaneous photosensitivity and bullae; sparse hair, eyebrows, and eyelashes; dystrophic nails; congenital cataracts and other ocular anomalies, including glaucoma, microphthalmia, and corneal opacities, with Peters anomaly and optic atrophy in 1 patient each; craniofacial dysmorphisms, including severe microcephaly; and skeletal anomalies, including osteopenia, platyspondyly, flared and/or irregular metaphyses, and short metacarpals and phalanges.

6/6 patients above age 2 years had short stature of more than 2 SDS below mean (-4.3 to -8.1SDS). Microcephaly was not severe at birth: between -0.3 to -2.3SDS, but progressed in all patients and was more than -3SDS in unrelated patients.
All 7 probands harboured a recurrent DNA2: c.588–2214A>G intronic variant, in addition to other DNA2 variants in trans: 5 individuals had intragenic exon deletions, one harboured missense variant c.143T>C, p.Leu48Pro (not reported in gnomaD), and sibs in Family 7 had a frameshift variant.

PMID: 40693833 Ay et al., 2025
Report of a female Turkish proband with Rothmund-Thomson syndrome and comp het DNA2 variants: deep intronic c.588-2214A>G and missense c.2519 T>C, Leu840Pro (not in gnomAD v4). She presented with hallmark features of the syndrome: short stature, poikiloderma, corneal dystrophy, bilateral cataracts, skin photosensitivity and blistering, hand contractures, dystrophic nails. Parents are non-consanguineous. Microcephaly not reported; her height was 76cm (-6.3SDS) at 4 yo.
Severe microcephaly v9.28 DNA2 Ida Ertmanska changed review comment from: PMID: 37055165 Di Lazzaro Filho et al., 2023; to: PMID: 37055165 Di Lazzaro Filho et al., 2023
Summary from OMIM 620819: Study reported 8 children from 7 families with Rothmund-Thomson syndrome and mutation in the DNA2 gene. 6 of the children were Brazilian and 2 were sibs of Swiss/Portuguese ancestry. Clinical findings included severe growth failure, with some individuals showing signs suggestive of growth hormone or combined pituitary hormone deficiency; widespread poikiloderma; cutaneous photosensitivity and bullae; sparse hair, eyebrows, and eyelashes; dystrophic nails; congenital cataracts and other ocular anomalies, including glaucoma, microphthalmia, and corneal opacities, with Peters anomaly and optic atrophy in 1 patient each; craniofacial dysmorphisms, including severe microcephaly; and skeletal anomalies, including osteopenia, platyspondyly, flared and/or irregular metaphyses, and short metacarpals and phalanges.
Severe microcephaly v9.28 DNA2 Ida Ertmanska reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37055165; Phenotypes: Rothmund-Thomson syndrome, type 4, OMIM:620819, Seckel syndrome 8, OMIM:615807, Rothmund-Thomson syndrome type 4, MONDO:0970950, Seckel syndrome 8, MONDO:0014350; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly v2.293 DNA2 Eleanor Williams Tag Q2_21_rating was removed from gene: DNA2.
Severe microcephaly v2.292 DNA2 Sarah Leigh commented on gene: DNA2
Severe microcephaly v2.291 DNA2 Eleanor Williams Source Expert Review Green was added to DNA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v2.144 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to 24389050; 31045292
Severe microcephaly v2.143 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from Seckel syndrome 8, OMIM:615807 to Seckel syndrome 8, OMIM:615807; Microcephalic primordial dwarfism, MONDO:0017950
Severe microcephaly v2.142 DNA2 Arina Puzriakova Tag Q2_21_rating tag was added to gene: DNA2.
Severe microcephaly v2.142 DNA2 Arina Puzriakova Classified gene: DNA2 as Amber List (moderate evidence)
Severe microcephaly v2.142 DNA2 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - 4 different homozygous variants identified in at least 5 unrelated families with microcephalic primordial dwarfism (PMIDs: 24389050; 31045292)
Severe microcephaly v2.142 DNA2 Arina Puzriakova Gene: dna2 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v2.141 DNA2 Arina Puzriakova Publications for gene: DNA2 were set to 24389050
Severe microcephaly v2.140 DNA2 Arina Puzriakova Phenotypes for gene: DNA2 were changed from ?Seckel syndrome 8, 615807; SCKL8 to Seckel syndrome 8, OMIM:615807
Severe microcephaly v2.20 DNA2 Zornitza Stark reviewed gene: DNA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 24389050, 31045292; Phenotypes: Seckel syndrome 8, MIM#615807; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Severe microcephaly v1.62 DNA2 Louise Daugherty reviewed gene: DNA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v1.61 DNA2 Louise Daugherty Source NHS GMS was added to DNA2.
Severe microcephaly DNA2 Rebecca Foulger marked DNA2 as ready
Severe microcephaly DNA2 Rebecca Foulger commented on DNA2
Severe microcephaly DNA2 Rebecca Foulger commented on DNA2