Rare syndromic craniosynostosis or isolated multisuture synostosis
Gene: AHDC1
Comment on list classification: There are three unrelated cases of Xia-Gibbs syndrome reported with craniosynostosis as one of their clinical manifestations and they all had different heterozygous variants. Hence, this gene can be promoted to GREEN in the next GMS update.Created: 6 May 2023, 5:18 a.m. | Last Modified: 6 May 2023, 5:19 a.m.
Panel Version: 4.9
A subset of patients with Xia-Gibbs syndrome (MIM #615829) presented with craniosynostosis as part of their clinical phenotype.
PMID:27884935 reported whole exome and genome sequencing analysis in a cohort of patients with undiagnosed craniosynostosis and identified one patient with a de novo variant (c.2373_2374delTG/ p.Cys791fs*57) in AHDC1. In addition to bicoronal and metopic craniosynostosis, the patient also had moderate developmental delay and hoarse cry.
PMID:30152016 reported the clinical phenotypes of five patients diagnosed with AHDC1-related Xia-Gibbs syndrome. Out of these five cases, one patient presented with bicoronal craniosynostosis in addition to intellectual disability and speech and motor delay and harboured a different heterozygous variant in AHDC1 (c.2473C > T/ p.Gln825*).
PMID:30858058 reported a two-year-old girl with developmental delay, brain anomalies, laryngomalacia and craniosynostosis and she was identified with a heterozygous variant (c.4370 A>G/ p.Asp1457Gly) in AHDC1.Created: 6 May 2023, 5:14 a.m. | Last Modified: 6 May 2023, 5:17 a.m.
Panel Version: 4.8
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Xia-Gibbs syndrome, OMIM:615829
Publications
• Whole exome sequencing identified a heterozygous missense variant c.4370A>G; p.(Asp1457Gly) in a child with developmental delay, lack of speech, seizures, structural brain anomalies, craniosynostosis, laryngomalacia and facial dysmorphism (Gumus, 2020).
• A whole exome and genome sequencing analysis in a cohort of patients with undiagnosed craniosynostosis identified one individual with bicoronal and metopic craniosynostosis and a de novo c.2373_2374delTG; p.(Cys791fs*57) variant in AHDC1 (Miller et al., 2017).
• A patient with bicoronal craniosynostosis was found by whole exome sequencing to harbour a heterozygous variant in AHDC1 (c.2473C > T; p.(Gln825*)) (Ritter et al., 2018).
• Two individuals with Xia-Gibbs syndrome were reported with de novo variants in AHDC1: c.3185_3186del; p.(Thr1062Serfs*63) and c.2772del; p.(Arg925Glufs*7) (Tønne et al., 2021).
• Two variants were detected in independent families (one with dolichocephaly and the other with brachycephaly, although it is not clear if craniosynostosis was radiologically confirmed) encoding frameshifting variants: c.1206delA; p.(Arg403Alafs*49) and c.1758delA; p.(Lys586Asnfs*37) (Danda et al., 2022).Created: 2 Mar 2023, 1:17 p.m. | Last Modified: 2 Mar 2023, 1:17 p.m.
Panel Version: 3.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mental retardation, failure to thrive, hypotonia, and delayed psychomotor development with absent or poor expressive language, mild dysmorphic features - 2 cases with CSS; Miller JMedGenet 17 and Ritter AmJMedGenet 18 ; Review on behalf of Tracy Lester and Andrew WilkieCreated: 5 Mar 2019, 11:33 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Xia-Gibbs syndrome - 615829
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 11:55 a.m. | Last Modified: 11 Oct 2023, 11:55 a.m.
Panel Version: 4.174
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: AHDC1; Suggested initial gene rating: amberCreated: 5 Mar 2019, 11:21 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q2_23_promote_green was removed from gene: AHDC1.
Source Expert Review Green was added to AHDC1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: AHDC1.
Gene: ahdc1 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: AHDC1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AHDC1 were set to
Phenotypes for gene: AHDC1 were changed from Xia-Gibbs syndrome 615829 to Xia-Gibbs syndrome, OMIM:615829
Added phenotypes Xia-Gibbs syndrome 615829 for gene: AHDC1
gene: AHDC1 was added gene: AHDC1 was added to Craniosynostosis. Sources: NHS GMS Mode of inheritance for gene: AHDC1 was set to