Chronic Thrombocytopenia as the Initial Manifestation of STIM1-Related Disorders

Area of Science:

• Genetics
• Pediatrics
• Immunology

Background:

• Pediatric thrombocytopenia presents a broad differential diagnosis.
• Genetic testing is increasingly utilized to determine the etiology of thrombocytopenia.
• Chronic thrombocytopenia can be associated with complex systemic symptoms.

Purpose of the Study:

• To report a novel case of pediatric thrombocytopenia with overlapping Stormorken syndrome phenotypes.
• To emphasize the importance of genetic testing in diagnosing complex pediatric hematologic disorders.
• To highlight the diagnostic utility of muscle enzyme evaluation in patients with thrombocytopenia and myopathic symptoms.

Main Methods:

• Case presentation of a 16-year-old male with chronic thrombocytopenia.
• Comprehensive laboratory evaluation including inflammatory markers and muscle enzymes.
• Diagnostic imaging (lymphadenopathy, asplenia) and muscle biopsy.
• Ophthalmological assessment.
• Genetic testing for STIM1 pathogenic variants.

Main Results:

• The patient presented with chronic thrombocytopenia, constitutional symptoms, hand edema, inflammation, elevated muscle enzymes, lymphadenopathy, asplenia, and myopathy.
• Genetic analysis identified a pathogenic STIM1 variant, consistent with autosomal dominant Stormorken syndrome.
• The observed phenotype demonstrated an overlap between previously described gain-of-function and loss-of-function STIM1 variants.

Conclusions:

• This case expands the phenotypic spectrum associated with STIM1 variants, blurring distinctions between related syndromes.
• Multidisciplinary care and genetic testing are crucial for managing chronic, unexplained pediatric thrombocytopenia.
• Elevated muscle enzymes should be considered in the workup of pediatric patients with thrombocytopenia and associated neuromuscular symptoms.