MIRAGE Syndrome
MIRAGE Syndrome
Introduction
MIRAGE syndrome is a rare multisystem disorder characterized by Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. First described in 2015, it is caused by pathogenic variants in the SAMD9 gene.
Key Points
- Acronym: MIRAGE (Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy)
- Inheritance: Autosomal dominant
- Gene: SAMD9
- Age of onset: Prenatal/neonatal period
Clinical Features
Growth & Development
- Severe intrauterine growth restriction (IUGR)
- Persistent postnatal growth failure
- Microcephaly
- Developmental delay in survivors
Hematologic Manifestations
- Bone marrow failure
- Myelodysplasia
- Increased risk of myeloid leukemia
- Cytopenia (affecting multiple cell lines)
- Recurrent infections due to neutropenia
Endocrine Abnormalities
- Primary adrenal insufficiency
- Adrenal hypoplasia or aplasia
- Disorders of sexual development (46,XY DSD)
- Ambiguous genitalia in genetic males
Gastrointestinal Features
- Chronic diarrhea
- Enteropathy
- Feeding difficulties
- Failure to thrive
Genetics & Pathophysiology
Genetic Basis
- Gene: SAMD9 (Sterile Alpha Motif Domain-containing 9)
- Location: Chromosome 7q21.2
- Inheritance pattern: Autosomal dominant
- De novo mutations in most cases
Molecular Mechanisms
- SAMD9 protein functions in endosome fusion
- Growth-restricting effects on cells
- Gain-of-function mutations lead to enhanced growth restriction
- Somatic reversion often occurs in blood cells
Diagnosis & Management
Diagnostic Criteria
- Clinical features (presence of core manifestations)
- Genetic testing revealing SAMD9 pathogenic variant
- Imaging studies showing adrenal hypoplasia
- Bone marrow examination showing dysplasia
Management Approach
- Multidisciplinary team care
- Glucocorticoid replacement therapy
- Management of infections
- Regular monitoring of blood counts
- Growth and development monitoring
- Nutritional support
Surveillance
- Regular assessment of bone marrow function
- Monitoring for myeloid malignancy development
- Growth and developmental assessment
- Endocrine evaluation
Prognosis & Monitoring
Survival & Outcomes
- High mortality rate in early childhood
- Variable prognosis depending on severity
- Better outcomes with early diagnosis and management
- Risk of hematologic complications throughout life
Long-term Monitoring
- Regular hematologic assessment
- Endocrine function monitoring
- Growth and development tracking
- Infection prevention strategies
