SEPTOOPTIC DYSPLASIA

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SEPTO-OPTIC DYSPLASIA
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SOD Definition

• Variable combination of midline forebrain
  abnormalities, eye abnormalities and pituitary
  abnormalities
• Rare reported incidence 1/50000 probably
  commoner
• 2/3 features to make the diagnosis
• Commoner in younger mothers

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Forebrain abnormalities

• In 75-80 of patients
• Absence of septum pellucidum
• Absence of corpus callosum
• Cerebellar hypoplasia
• Schizencephaly

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Consequences of forebrain anomalies

• Fits
• Behavioural difficulties
• Learning difficulties
• Developmental delay
• Hemiplegia

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Optic nerve hypoplasia

• Unilateral/bilateral
• Bilateral commoner
• Associated with anopthalmia/micropthalmia
• Visual impairment variable - complete to
  compensated

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Pituitary gland

• Develops from the oral cavity in the embryo and
  the brain (hypothalamus)
• 5 different cell types in anterior pituitary
  producing 6 different hormones
• Secretion of hormones regulated by hypothalamus

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Anterior pituitary gland

• Growth hormone growth and helps maintain normal
  blood sugar levels in children increases bone
  strength, muscle mass and decreases fat mass and
  heart disease in adults
• ACTH regulates production of cortisol and
  androgens from adrenal glands cortisol essential
  for normal well-being and to fight stress and
  infection

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Anterior pituitary gland

• Prolactin important for lactation, ?immune
  system
• FSH, LH important for puberty and fertility LH
  important for normal development of males and for
  descent of testes into scrotum
• TSH important for regulation of thyroid gland
  and thyroxine production

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Posterior pituitary gland

• Vasopressin important for normal fluid balance -
  retains water by controlling reabsorption of
  water in kidney tubules
• Oxytocin important for parturition (birth) and
  ejection of milk

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Pituitary Hormone Deficiency

• GH poor growth with eventual short stature,
  possibly increased incidence of myocardial
  infarction
• Prolactin no lactation
• ACTH low cortisol leading to low blood sugar,
  lethargy, inability to fight stress and
  infection, low blood pressure, low sodium level
  in blood, collapse

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Pituitary Hormone Deficiency

• FSH, LH inadequate sexual development in males,
  lack of puberty, lack of fertility
• TSH lack of thyroxine with slowness, cold
  intolerance, constipation, growth failure, mental
  retardation if not picked up early
• Vasopressin diabetes insipidus with excessive
  urinary output

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Complexity of hypothalamo-pituitary development

• Early puberty can be explained on basis of
  hypothalamic involvement
• Occasionally mixed involvement of hypothalamus
  and pituitary

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Clinical features of SOD

• Conjugated jaundice
• Neurological features
• Variable visual loss
• Impaired sense of smell
• Endocrine features
• Behavioural disturbances eg. autism
• Sleep disturbance

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MRI SCANS OF SOD PATIENTS
CONTROL
SIBLING 2
SIBLING 1
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Management of SOD

• Support from Neurologists and Opthalmologists
  treatment of convulsions
• Mainstay of treatment endocrine

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Endocrine replacement

• Growth hormone daily subcutaneous injections
• Hydrocortisone X3 doses daily adjustment with
  illness/stress
• DDAVP nasal/oral
• Thyroxine
• Ethinyloestradiol/testosterone

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Investigations

• MRI scan of brain
• Visual evoked responses/electroretinogram
• Routine electrolyte measurement
• Thyroid function tests
• Pituitary function tests glucagon/insulin/LHRH/TR
  H - in tertiary centres ideally
• Fluid balance

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Monitoring

• Evolving - new endocrine features may develop
• Monitoring of growth rate at regular intervals
• Monitoring through puberty
• Regular checks of thyroid function, watch fluid
  balance

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Long-term outlook

• Short stature
• Developmental/intellectual impairment
• Fits, hemiparesis etc
• Impaired fertility
• Visual impairment
• Sleep/behavioural difficulties
• Obesity

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Why do you get SOD?

• Development of pituitary gland, forebrain,
  olfactory bulbs and eyes all from the same part
  of the early embryo. Problems occur at 3-6 weeks
  of gestation
• Environment and teratogens
• Familial cases dominant or recessive

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Genetics of SOD

• Mutations in HESX1 Dominant or recessive
• Occasionally, one abnormal copy of gene carried
  with no phenotype in parent but child affected
• Number of other developmental genes may also be
  involved all extrapolated from animal studies

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Research

• New genes involved in SOD what is their function
• Why the variability in severity
• Sleep/wake cycles in children with SOD and
  hypothalamic involvement and the use of melatonin
  (10-18 year olds)