Perlman Syndrome
Perlman Syndrome
Overview
Perlman syndrome is an extremely rare autosomal recessive overgrowth disorder characterized by fetal gigantism, renal abnormalities, and a high predisposition to Wilms tumor. It is caused by biallelic mutations in the DIS3L2 gene.
Key Points
- Inheritance: Autosomal recessive
- Gene: DIS3L2 (2q37.1)
- Prevalence: Extremely rare (<30 cases reported)
- Age of Onset: Prenatal
- High mortality rate in neonatal period
Clinical Features
Prenatal Findings
- Polyhydramnios
- Fetal overgrowth
- Enlarged kidneys
- Ascites
- Macrosomia
- Visceromegaly
Neonatal Features
- Macrosomia (>97th percentile)
- Hypotonia
- Respiratory difficulties
- Feeding problems
- Neonatal diabetes (in some cases)
Facial Characteristics
- Prominent forehead
- Deep-set eyes
- Broad nasal bridge
- Low-set ears
- Depressed nasal bridge
- Micrognathia
Renal Manifestations
- Nephromegaly
- Bilateral nephroblastomatosis
- High risk of Wilms tumor (>60%)
- Renal dysplasia
- Hydronephrosis
Other Features
- Organomegaly
- Hepatomegaly
- Splenomegaly
- Enlarged pancreas
- Cryptorchidism in males
- Developmental delay in survivors
- Visual problems
Diagnosis & Genetics
Diagnostic Criteria
- Prenatal ultrasound findings
- Clinical features
- Molecular genetic testing
- Histological examination of renal tissue
Genetic Testing
- DIS3L2 gene sequencing
- Deletion/duplication analysis
- Family history assessment
- Parental carrier testing
Differential Diagnosis
- Beckwith-Wiedemann syndrome
- Simpson-Golabi-Behmel syndrome
- Sotos syndrome
- Nephroblastomatosis without syndrome
- Isolated Wilms tumor
Prenatal Diagnosis
- Serial ultrasound monitoring
- Fetal MRI when indicated
- Molecular testing if familial mutation known
- Assessment of fetal kidneys and growth
Management & Surveillance
Initial Management
- Neonatal intensive care
- Respiratory support
- Feeding support
- Genetic counseling
Surveillance Protocol
- Renal monitoring
- Regular ultrasound (every 3-4 months)
- MRI when indicated
- Renal function tests
- Growth monitoring
- Developmental assessments
- Endocrine evaluation
Oncological Surveillance
- Regular abdominal imaging
- Monitoring for Wilms tumor
- Early detection protocols
- Consideration for prophylactic nephrectomy
Supportive Care
- Physical therapy
- Occupational therapy
- Developmental support
- Family support services
Prognosis & Long-term Care
Survival Rates
- High neonatal mortality (>50%)
- Causes of death
- Respiratory failure
- Renal failure
- Sepsis
- Complications of prematurity
Long-term Complications
- Developmental delay
- Intellectual disability
- Visual impairment
- Renal complications
- Risk of malignancy
Quality of Life Considerations
- Regular medical follow-up
- Educational support
- Family adaptation
- Psychosocial support
