Rare syndromic craniosynostosis or isolated multisuture synostosis

Gene: AHDC1

Green List (high evidence)

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

• 27884935
• 30152016
• 30858058

Green List (high evidence)

• 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

I don't know

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 Wilkie

Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Xia-Gibbs syndrome - 615829

Green List (high evidence)

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: amber

Created: 5 Mar 2019, 11:21 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted