AIFM1-associated X-linked spondylometaphyseal dysplasia with cerebral hypomyelination
Katharine Edgerley1, Angela Barnicoat2, Amaka C Offiah3
1Department of Clinical Genetics, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom.
Abstract:
Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD-H) is a very rare but distinctive phenotype, unusually combining spondylometaphyseal dysplasia with hypomyelinating leukodystrophy. Recently, SMD-H has been associated with variants confined to a specific intra-genic locus involving Exon 7, suggesting that AIFM1 plays an important role in bone development and metabolism as well as cerebral myelination. Here we describe two further affected boys, one with a novel intronic variant associated with skipping of Exon 7 of AIFM1 and the other a synonymous variant within Exon 7 of AIFM1. We describe their clinical course and radiological and genetic findings, providing further insight into the natural history of this condition.
Insights
Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD-H) is linked to AIFM1 gene variants. This study details two new cases, expanding understanding of this rare disorder affecting bone and brain development.
Area of Science:
- Genetics
- Neurology
- Skeletal Dysplasias
Background:
- Spondylometaphyseal dysplasia with cerebral hypomyelination (SMD-H) is a rare condition characterized by skeletal abnormalities and impaired brain myelination.
- Recent research links SMD-H to variants in the AIFM1 gene, specifically within Exon 7, highlighting its role in bone and cerebral development.
Observation:
- This study reports on two additional male patients diagnosed with SMD-H.
- One patient presented with a novel intronic variant causing Exon 7 skipping in AIFM1.
- The second patient had a synonymous variant within Exon 7 of the AIFM1 gene.
Findings:
- Detailed clinical, radiological, and genetic analyses were performed for both patients.
- The findings provide further evidence for AIFM1's critical role in SMD-H.
- The study contributes to a deeper understanding of the condition's genetic underpinnings.
Implications:
- These cases expand the known spectrum of AIFM1 variants associated with SMD-H.
- The research offers valuable insights into the natural history and clinical course of this rare disorder.
- Further investigation into AIFM1's function may reveal therapeutic targets for SMD-H and related conditions.
