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| Skeletal dysplasia v10.20 | ANTXR1 |
Ida Ertmanska changed review comment from: PMID: 40962491 Modafferi et al., 2025 Review of 105 GAPO syndrome cases + new case: report of a 33yo woman with GAPO syndrome a homozygous ANTXR1 deletion of exons 4, 5, and 6. The newly reported individual had short stature (130cm), craniofacial abnormalities, absence of several dental elements, liver disease/hepatomegaly, blindness secondary to optic atrophy, alopecia, primary amenorrhea, and progeroid appearance of the skin. Literature review describes a common phenotype: growth impairment, alopecia, sparse dentition (97/105), long bone dysplasia, optic atrophy (48/105) & other ocular features. Intellectual disability is not a common feature of the syndrome - cognitive function was explicitly reported to be normal in 27 cases, and not mentioned in others. Both missense, splice, and frameshift variants in ANTXR1 have been reported to cause GAPO syndrome. PMID: 38423276 Balakrishnan, Goud, & Teegala, 2024 Report of an Indian proband, 3.75yrs old female, with GAPO syndrome. She presented with short stature, reduced length of long bones, dysmorphism, sparse hair growth & lack of appropriate dentition. She was born with sagittal craniosynostosis and right club foot. Patient was noted to have mild dev delay with preserved intellect and social skills. Her head circumference was 49.5 cms (-1.1 Z score), height was 82 cms (−4.5 Z score). Trio exome detected a homozygous ANTXR1 NM_032208.3: c.568delC (p. Arg190GlyfsTer12) variant in the proband - het in parents. PMID: 30575274 Abdel-Hamid et al., 2019 Report of 7 patients from 5 unrelated consanguineous Egyptian families with GAPO syndrome and ANTXR1 variants. Common phenotype: alopecia, pseudoadontia, micrognathia, dysmorphism (e.g., frontal bossing, hypertelorism) optic atrophy (6/7), glaucoma (unilateral or bilateral), short stature, microcephaly (7/7, including 3 unrelated patients with severe microcephaly of more than -3 SD), joint hyperextensibility. Craniosynostosis and keratopathy noted in only 1/7 individuals. Intellectual disability not reported. Individuals harboured 5 different homozygous ANTXR1 variants: 2 splice variants, 2 frameshift variants, and 1 deletion. Their parents were heterozygous and unaffected. ANTXR1 association with AR GAPO syndrome is classified as Definitive in ClinGen (Syndromic Disorders GCEP, July 2025). This gene is associated with AR GAPO syndrome, OMIM:230740 in OMIM (accessed 23rd Oct 2026). Sources: Literature; to: PMID: 40962491 Modafferi et al., 2025 Review of 105 GAPO syndrome cases + new case: report of a 33yo woman with GAPO syndrome a homozygous ANTXR1 deletion of exons 4, 5, and 6. The newly reported individual had short stature (130cm), craniofacial abnormalities, absence of several dental elements, liver disease/hepatomegaly, blindness secondary to optic atrophy, alopecia, primary amenorrhea, and progeroid appearance of the skin. Literature review describes a common phenotype: growth impairment, alopecia, sparse dentition (97/105), long bone skeletal dysplasia (more rarely with additional features of metaphyseal abnormalities, epiphysial enlargement, bone thickening, arched bone profile and tubular disarrangement), optic atrophy (48/105) & other ocular features. Intellectual disability is not a common feature of the syndrome - cognitive function was explicitly reported to be normal in 27 cases, and not mentioned in others. Both missense, splice, and frameshift variants in ANTXR1 have been reported to cause GAPO syndrome. PMID: 38423276 Balakrishnan, Goud, & Teegala, 2024 Report of an Indian proband, 3.75yrs old female, with GAPO syndrome. She presented with short stature, reduced length of long bones, dysmorphism, sparse hair growth & lack of appropriate dentition. She was born with sagittal craniosynostosis and right club foot. Patient was noted to have mild dev delay with preserved intellect and social skills. Her head circumference was 49.5 cms (-1.1 Z score), height was 82 cms (−4.5 Z score). Trio exome detected a homozygous ANTXR1 NM_032208.3: c.568delC (p. Arg190GlyfsTer12) variant in the proband - het in parents. PMID: 30575274 Abdel-Hamid et al., 2019 Report of 7 patients from 5 unrelated consanguineous Egyptian families with GAPO syndrome and ANTXR1 variants. Common phenotype: alopecia, pseudoadontia, micrognathia, dysmorphism (e.g., frontal bossing, hypertelorism) optic atrophy (6/7), glaucoma (unilateral or bilateral), short stature, microcephaly (7/7, including 3 unrelated patients with severe microcephaly of more than -3 SD), joint hyperextensibility. Craniosynostosis and keratopathy noted in only 1/7 individuals. Intellectual disability not reported. Individuals harboured 5 different homozygous ANTXR1 variants: 2 splice variants, 2 frameshift variants, and 1 deletion. Their parents were heterozygous and unaffected. ANTXR1 association with AR GAPO syndrome is classified as Definitive in ClinGen (Syndromic Disorders GCEP, July 2025). This gene is associated with AR GAPO syndrome, OMIM:230740 in OMIM (accessed 23rd Oct 2026). Sources: Literature |
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| Skeletal dysplasia v10.20 | ANTXR1 |
Ida Ertmanska gene: ANTXR1 was added gene: ANTXR1 was added to Skeletal dysplasia. Sources: Literature Q4_26_promote_green tags were added to gene: ANTXR1. Mode of inheritance for gene: ANTXR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ANTXR1 were set to 30575274; 38423276; 40962491 Phenotypes for gene: ANTXR1 were set to GAPO syndrome, OMIM:230740; GAPO syndrome, MONDO:0009263; Growth delay-alopecia-pseudoanodontia-optic atrophy syndrome Review for gene: ANTXR1 was set to GREEN Added comment: PMID: 40962491 Modafferi et al., 2025 Review of 105 GAPO syndrome cases + new case: report of a 33yo woman with GAPO syndrome a homozygous ANTXR1 deletion of exons 4, 5, and 6. The newly reported individual had short stature (130cm), craniofacial abnormalities, absence of several dental elements, liver disease/hepatomegaly, blindness secondary to optic atrophy, alopecia, primary amenorrhea, and progeroid appearance of the skin. Literature review describes a common phenotype: growth impairment, alopecia, sparse dentition (97/105), long bone dysplasia, optic atrophy (48/105) & other ocular features. Intellectual disability is not a common feature of the syndrome - cognitive function was explicitly reported to be normal in 27 cases, and not mentioned in others. Both missense, splice, and frameshift variants in ANTXR1 have been reported to cause GAPO syndrome. PMID: 38423276 Balakrishnan, Goud, & Teegala, 2024 Report of an Indian proband, 3.75yrs old female, with GAPO syndrome. She presented with short stature, reduced length of long bones, dysmorphism, sparse hair growth & lack of appropriate dentition. She was born with sagittal craniosynostosis and right club foot. Patient was noted to have mild dev delay with preserved intellect and social skills. Her head circumference was 49.5 cms (-1.1 Z score), height was 82 cms (−4.5 Z score). Trio exome detected a homozygous ANTXR1 NM_032208.3: c.568delC (p. Arg190GlyfsTer12) variant in the proband - het in parents. PMID: 30575274 Abdel-Hamid et al., 2019 Report of 7 patients from 5 unrelated consanguineous Egyptian families with GAPO syndrome and ANTXR1 variants. Common phenotype: alopecia, pseudoadontia, micrognathia, dysmorphism (e.g., frontal bossing, hypertelorism) optic atrophy (6/7), glaucoma (unilateral or bilateral), short stature, microcephaly (7/7, including 3 unrelated patients with severe microcephaly of more than -3 SD), joint hyperextensibility. Craniosynostosis and keratopathy noted in only 1/7 individuals. Intellectual disability not reported. Individuals harboured 5 different homozygous ANTXR1 variants: 2 splice variants, 2 frameshift variants, and 1 deletion. Their parents were heterozygous and unaffected. ANTXR1 association with AR GAPO syndrome is classified as Definitive in ClinGen (Syndromic Disorders GCEP, July 2025). This gene is associated with AR GAPO syndrome, OMIM:230740 in OMIM (accessed 23rd Oct 2026). Sources: Literature |
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| Skeletal dysplasia v9.32 | FAM210A |
Achchuthan Shanmugasundram gene: FAM210A was added gene: FAM210A was added to Skeletal dysplasia. Sources: Literature Q3_26_promote_green tags were added to gene: FAM210A. Mode of inheritance for gene: FAM210A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM210A were set to 42410297 Phenotypes for gene: FAM210A were set to Spondyloepimetaphyseal dysplasia with tracheal stenosis and ectodermal dysplasia, OMIM:621650 Review for gene: FAM210A was set to GREEN Added comment: PMID:42410297 (2026) reported five patients from four unrelated families with skeletal dysplasia phenotype characterised by spondyloepimetaphyseal dysplasiachondrodysplasia with short stature (all patents), tracheal stenosis (all patients), conical teeth and/or early tooth decay, and sparse hair suggestive of ectodermal dysplasia (in three unrelated patients). They were identified with biallelic variants in FAM210A gene (new gene name - MIMS1) - homozygous missense variants in three families and compound heterozygous nonsense variants in the first family with two siblings. This gene has been associated with relevant phenotype in OMIM (MIM #621650, last accessed 24 July 2026), but not in Gene2Phenotype or ClinGen. Sources: Literature |
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| Skeletal dysplasia v6.11 | ARSK | Sarah Leigh Phenotypes for gene: ARSK were changed from Mucopolysaccharidoses with short stature, coarse facial features and dysostosis multiplex to Mucopolysaccharidosis, type X, OMIM:619698; mucopolysaccharidosis, type 10, MONDO:0030524 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v4.35 | NEPRO |
Achchuthan Shanmugasundram changed review comment from: PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys). PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant. PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant. This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype.; to: PMID:26633546 reported a sister and brother among 31 Saudi Arabian families studied with skeletal dysplasia and homozygous missense variant in NEPRO gene (p.Arg49Cys). PMID:29620724 reported the same homozygous NEPRO variant (p.Arg49Cys) in two brothers of Arab descent with skeletal dysplasia. The disorder is identical to phenotypes reported in PMID:26633546 and haplotype analysis confirmed the founder nature of the variant. PMID:31250547 reported a 13-year-old Indian girl with a different homozygous missense variant (p.Leu145Phe) and with severe short stature and skeletal dysplasia with sparse scalp hair and skin and joint laxity. Her second-cousin parents were heterozygous for the same variant. PMID:37294112 reported a 7-year-old girl from an Arabic-speaking community in Eastern Africa with Anauxetic dysplasia 3 and another homozygous NEPRO variant (p.Arg94Cys). She was born to consanguineous parents, who reported that their shared ancestor was of Arab descent. This patient presented with clinically relevant features not previously described in ANXD3: atlantoaxial subluxation, extensive dental anomalies, and a sagittal suture craniosynostosis resulting in scaphocephaly. This gene has been associated with relevant phenotypes in OMIM (MIM #618853), but not in Gene2Phenotype. |
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| Skeletal dysplasia v2.223 | ARSK |
Arina Puzriakova gene: ARSK was added gene: ARSK was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARSK were set to 34916232 Phenotypes for gene: ARSK were set to Mucopolysaccharidoses with short stature, coarse facial features and dysostosis multiplex Review for gene: ARSK was set to AMBER Added comment: Verheyen et al. 2022 (PMID: 34916232) reported four affected individuals of two unrelated consanguineous families with homozygous variants c.250C>T, p.(Arg84Cys) and c.560T>A, p.(Leu187Ter) in ARSK, respectively. Patients were affected with skeletal dysplasia, resembling spondyloepiphysial dysplasia. Reverse phenotyping in two individuals from one family revealed additional cardiac and ophthalmological abnormalities. Sources: Literature |
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| Skeletal dysplasia v2.70 | GZF1 | Eleanor Williams Phenotypes for gene: GZF1 were changed from Larsen syndrome to Larsen syndrome; joint laxity, short stature, and myopia OMIM:617662; joint laxity, short stature, and myopia MONDO:0060556 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v2.21 | GZF1 | Zornitza Stark reviewed gene: GZF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33009817; Phenotypes: Joint laxity, short stature, and myopia, MIM# 617662, Larsen-like syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.193 | ARSE | Louise Daugherty Tag new-gene-name tag was added to gene: ARSE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.193 | ARSE | Louise Daugherty commented on gene: ARSE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.166 | GZF1 |
Eleanor Williams commented on gene: GZF1: Associated with Joint laxity, short stature, and myopia (#617662) in OMIM and with LARSEN SYNDROME (probable) in Gene2Phenotype. Generalized joint laxity is listed as a phenotype for Larsen syndrome in Gene2Phenotype. PMID: 28475863 - Patel et al 2017 - 2 cases. Family 1 - a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia. The index patient also had severe kyphoscoliosis. Both the index patient and her brother had short stature. A homozygous truncating variant in GZF1 was identified (c.865G>T (pGlu289∗). Family 2 - another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement (generalized joint laxity) A second homozygous truncating GZF1 variant was identified (c.1054dup (p.Thr352Asnfs∗50). Neither variant was present in 2,379 Saudi exomes or the Exome Aggregation Consortium (ExAC) Browser. In functional studies they found using immunofluorescence, strong localization of GZF1 in the developing mouse eye and, to a lesser extent, in the mesenchyme of the developing mouse limb buds. Using 3 patient-derived lymphoblastoid cell lines they found 1,095 genes to be dysregulated in affected individuals. |
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| Skeletal dysplasia v1.153 | CHST3 | Eleanor Williams Added phenotypes Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) 143095 for gene: CHST3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | GZF1 | Eleanor Williams Added phenotypes Larsen syndrome for gene: GZF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | B3GAT3 | Eleanor Williams Added phenotypes Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects, 245600; Larsen alike phenotype (skd incl) for gene: B3GAT3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | ARSE | Eleanor Williams Added phenotypes CDPXL; Chondrodysplasia punctata, X-linked recessive, 302950; CHONDRODYSPLASIA PUNCTATA 1, X-LINKED; X-linked recessive chondrodysplasia punctata for gene: ARSE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.153 | FLNB | Eleanor Williams Added phenotypes Spondylocarpotarsal synostosis syndrome 272460; Atelosteogenesis, type III 108721; Boomerang dysplasia 112310; Atelosteogenesis, type I 108720; Larsen syndrome 150250 for gene: FLNB | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | GZF1 | Tracy Lester reviewed gene: GZF1: Rating: AMBER; Mode of pathogenicity: ; Publications: 28475863; Phenotypes: Larsen syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | FLNB | Tracy Lester reviewed gene: FLNB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Atelosteogenesis, type I 108720, Atelosteogenesis, type III 108721, Boomerang dysplasia 112310, Larsen syndrome 150250, Spondylocarpotarsal synostosis syndrome 272460; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | CHST3 | Tracy Lester reviewed gene: CHST3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) 143095; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | B3GAT3 | Tracy Lester reviewed gene: B3GAT3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Larsen alike phenotype (skd incl), Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects, 245600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | ARSE | Tracy Lester reviewed gene: ARSE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: CDPXL, Chondrodysplasia punctata, X-linked recessive, 302950, X-linked recessive chondrodysplasia punctata, CHONDRODYSPLASIA PUNCTATA 1, X-LINKED; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.146 | ARSE | Eleanor Williams reviewed gene: ARSE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.145 | ARSE |
Eleanor Williams Source NHS GMS was added to ARSE. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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