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