Galloway-Mowat Syndrome
Galloway-Mowat Syndrome
Introduction
Galloway-Mowat syndrome (GMS) is a rare genetic disorder characterized by the triad of central nervous system abnormalities, early-onset nephrotic syndrome, and microcephaly. First described by Galloway and Mowat in 1968, it represents a complex neurodegenerative disorder with variable manifestations.
Key Points
- Inheritance: Usually autosomal recessive
- Major features: Microcephaly, nephrotic syndrome, brain anomalies
- Age of onset: Early infancy
- Multiple genes implicated: WDR73, LAGE3, OSGEP, TP53RK, TPRKB
Clinical Features
Neurological Manifestations
- Microcephaly (primary or progressive)
- Developmental delay
- Seizures (various types)
- Hypotonia
- Cerebellar signs
- Brain anomalies:
- Cerebral atrophy
- Cerebellar hypoplasia
- White matter changes
- Migration defects
Renal Features
- Early-onset nephrotic syndrome
- Proteinuria
- Renal histology:
- Minimal change disease
- Focal segmental glomerulosclerosis
- Diffuse mesangial sclerosis
- Progressive renal failure
Dysmorphic Features
- Characteristic facies
- Hypertelorism
- Large ears
- Micrognathia
- Short neck
- Growth retardation
Other Systems
- Skeletal abnormalities
- Hiatal hernia
- Visual impairment
- Contractures
- Growth failure
Genetics & Pathophysiology
Genetic Basis
- Primary genes:
- WDR73 (major cause)
- KEOPS complex genes (LAGE3, OSGEP, TP53RK, TPRKB)
- Other genes still being identified
- Inheritance patterns:
- Mainly autosomal recessive
- Genetic heterogeneity
- Variable expressivity
Molecular Mechanisms
- Disrupted microtubule function
- Podocyte dysfunction
- Neuronal migration defects
- Cellular proliferation abnormalities
- tRNA modification defects (KEOPS complex)
Pathological Findings
- Brain histology:
- Neuronal migration defects
- Cortical dysplasia
- Cerebellar abnormalities
- Kidney histology:
- Podocyte foot process effacement
- Glomerular basement membrane changes
- Variable patterns of glomerulosclerosis
Diagnosis & Management
Diagnostic Approach
- Clinical criteria:
- Early-onset nephrotic syndrome
- Microcephaly
- Neurological abnormalities
- Imaging studies:
- Brain MRI
- Renal ultrasound
- Laboratory testing:
- Urinalysis
- Renal function tests
- Genetic testing
- Renal biopsy
Management Strategies
- Multidisciplinary approach
- Nephrotic syndrome management:
- ACE inhibitors
- Immunosuppressive therapy
- Dialysis when needed
- Renal transplantation consideration
- Neurological care:
- Anticonvulsant therapy
- Developmental support
- Physical therapy
- Occupational therapy
- Supportive care:
- Nutritional support
- Growth monitoring
- Respiratory care
Prognosis & Complications
Prognosis Factors
- Age of onset
- Severity of neurological involvement
- Rate of renal deterioration
- Genetic variant type
Complications
- Renal complications:
- End-stage renal disease
- Infections
- Thrombotic events
- Neurological complications:
- Progressive neurodegeneration
- Intractable seizures
- Developmental regression
- Other complications:
- Growth failure
- Respiratory infections
- Feeding difficulties
Long-term Monitoring
- Regular neurological assessment
- Renal function monitoring
- Growth and development tracking
- Quality of life assessment
