SATB2 Variants in Glass Syndrome: the Clinical Impact of Novel Variants in the context of Misleading Diagnoses.
Laboratory Genetics and Genomics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction
SATB2 associated syndrome (SAS), or Glass syndrome (MIM 612313), which entails multisystemic developmental delay with dysmorphic features, can be distinguished from Mabry syndrome (MIM 239300) because SAS lacks hyperphosphatasia necessary to diagnose Mabry syndrome.
Case Presentation
We present a discussion of two patients with SATB2 variants that may be associated with SATB2 associated syndrome (SAS), or Glass syndrome, for whom Mabry syndrome was initially considered in the differential diagnosis.
Diagnostic Workup
The first patient with an SATB2 variant displayed Glass syndrome features. They were initially considered for Mabry syndrome due to concurrent hyperphosphatasia. The second patient, with potential Glass syndrome, had additional features including seizures, arachnodactyly, and a happy demeanor; a phenotype distinct from his brother with Mabry syndrome. We ruled out the differential diagnosis of Mabry syndrome in the second patient because hyperphosphatasia was absent and there were no likely biallelic pathogenic variants in GPI biosynthesis or remodeling genes.
Treatment and Management
Treatment of both patients intended to slow the progression. The second patient received surgical intervention for seizures in the 1980s and is currently seizure free.
Outcome and Follow-Up
In the first patient, we identified the SATB2(NM_001172517.1):c.400del; (p.Ala134HisfsTer17) variant, suggesting autosomal dominant Glass syndrome. No likely biallelic pathogenic variants were identified by exon sequencing of GPI biosynthesis and remodeling pathway genes. In the second patient we identified a likely de novo SATB2(NM_001172517.1):c.1733C>T (p.Pro578Leu) variant.
Discussion
Our preliminary analysis suggests that the first patient's Glass syndrome is linked to SATB2 variant. We discuss the de novo mutation identified in the second patient, which remains a VUS that requires further investigation.
Conclusion
We discuss phenotypic features, including alkaline phosphatase levels, facial dysmorphology, bone density, and metabolic profile, that can be used to distinguish Glass syndrome and Mabry syndrome.
SATB2 associated syndrome (SAS), or Glass syndrome (MIM 612313), which entails multisystemic developmental delay with dysmorphic features, can be distinguished from Mabry syndrome (MIM 239300) because SAS lacks hyperphosphatasia necessary to diagnose Mabry syndrome.
Case Presentation
We present a discussion of two patients with SATB2 variants that may be associated with SATB2 associated syndrome (SAS), or Glass syndrome, for whom Mabry syndrome was initially considered in the differential diagnosis.
Diagnostic Workup
The first patient with an SATB2 variant displayed Glass syndrome features. They were initially considered for Mabry syndrome due to concurrent hyperphosphatasia. The second patient, with potential Glass syndrome, had additional features including seizures, arachnodactyly, and a happy demeanor; a phenotype distinct from his brother with Mabry syndrome. We ruled out the differential diagnosis of Mabry syndrome in the second patient because hyperphosphatasia was absent and there were no likely biallelic pathogenic variants in GPI biosynthesis or remodeling genes.
Treatment and Management
Treatment of both patients intended to slow the progression. The second patient received surgical intervention for seizures in the 1980s and is currently seizure free.
Outcome and Follow-Up
In the first patient, we identified the SATB2(NM_001172517.1):c.400del; (p.Ala134HisfsTer17) variant, suggesting autosomal dominant Glass syndrome. No likely biallelic pathogenic variants were identified by exon sequencing of GPI biosynthesis and remodeling pathway genes. In the second patient we identified a likely de novo SATB2(NM_001172517.1):c.1733C>T (p.Pro578Leu) variant.
Discussion
Our preliminary analysis suggests that the first patient's Glass syndrome is linked to SATB2 variant. We discuss the de novo mutation identified in the second patient, which remains a VUS that requires further investigation.
Conclusion
We discuss phenotypic features, including alkaline phosphatase levels, facial dysmorphology, bone density, and metabolic profile, that can be used to distinguish Glass syndrome and Mabry syndrome.