de Morsier Syndrome (Septo-optic Dysplasia)

Introduction

De Morsier syndrome, also known as Septo-optic Dysplasia (SOD), is a rare congenital disorder characterized by the classic triad of optic nerve hypoplasia, midline brain defects, and pituitary hormone deficiencies. First described by Georges de Morsier in 1956, it represents a complex developmental disorder with variable manifestations.

Key Points

• Alternative names: Septo-optic Dysplasia (SOD), De Morsier's syndrome, Optic Nerve Hypoplasia-Septo-optic Dysplasia
• Incidence: 1 in 10,000 live births
• Classic triad present in only 30% of cases
• Variable expressivity and penetrance
• Major genes involved: HESX1, SOX2, SOX3

Clinical Features

Ophthalmic Manifestations

• Optic nerve hypoplasia (uni- or bilateral)
• Visual impairment (variable severity)
• Nystagmus
• Strabismus
• Visual field defects
• Associated eye abnormalities:
  • Microphthalmia
  • Aniridia
  • Colobomas

Neurological Features

• Midline brain defects:
  • Absent septum pellucidum
  • Corpus callosum abnormalities
  • Schizencephaly
• Developmental delay
• Seizures
• Motor delays
• Cognitive impairment
• Sleep disorders

Endocrine Abnormalities

• Hypopituitarism (variable presentation):
  • Growth hormone deficiency
  • Central hypothyroidism
  • ACTH deficiency
  • Diabetes insipidus
  • Gonadotropin deficiency
• Growth failure
• Delayed puberty
• Temperature dysregulation

Associated Features

• Feeding difficulties
• Sleep-wake cycle disturbances
• Behavioral problems
• Autism spectrum features
• Obesity

Genetics & Pathophysiology

Genetic Basis

• Primary genes:
  • HESX1 (most common)
  • SOX2
  • SOX3
  • OTX2
  • PROKR2
• Inheritance patterns:
  • Usually sporadic
  • Some familial cases (autosomal recessive/dominant)
  • Variable expressivity

Environmental Risk Factors

• Young maternal age
• Primiparity
• Maternal diabetes
• Viral infections during pregnancy
• Vascular disruption
• Teratogenic exposures

Developmental Mechanisms

• Disrupted prosencephalic development
• Abnormal neural crest migration
• Impaired pituitary organogenesis
• Defective optic nerve development

Diagnosis & Management

Diagnostic Approach

• Clinical evaluation:
  • Ophthalmological examination
  • Endocrine assessment
  • Neurological examination
  • Developmental assessment
• Imaging studies:
  • Brain MRI
  • Optical coherence tomography
  • Visual evoked potentials
• Laboratory testing:
  • Endocrine function tests
  • Genetic testing
  • Metabolic screening

Essential Assessments

• Regular growth monitoring
• Visual function assessment
• Endocrine function testing
• Developmental screening
• Neuropsychological evaluation

Treatment & Follow-up

Multidisciplinary Management

• Endocrine treatment:
  • Hormone replacement therapy
  • Growth hormone supplementation
  • Thyroid hormone replacement
  • Cortisol replacement
  • Stress dose protocols
• Ophthalmological care:
  • Visual aids
  • Strabismus management
  • Regular vision monitoring
• Developmental support:
  • Early intervention
  • Physical therapy
  • Occupational therapy
  • Speech therapy

Long-term Follow-up

• Regular endocrine monitoring
• Growth assessment
• Visual function checks
• Developmental tracking
• Psychological support
• Educational support

Emergency Management

• Adrenal crisis prevention/management
• Sick day rules
• Emergency protocols
• Parent/caregiver education