Transcript SEPTO-OPTIC DYSPLASIA

SEPTO-OPTIC
DYSPLASIA
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
Forebrain abnormalities
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In 75-80% of patients
Absence of septum pellucidum
Absence of corpus callosum
Cerebellar hypoplasia
Schizencephaly
Consequences of forebrain
anomalies
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Fits
Behavioural difficulties
Learning difficulties
Developmental delay
Hemiplegia
Optic nerve hypoplasia
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Unilateral/bilateral
Bilateral commoner
Associated with anopthalmia/micropthalmia
Visual impairment variable - complete to
compensated
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
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
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
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
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
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
Complexity of hypothalamopituitary development
• Early puberty: can be explained on basis of
hypothalamic involvement
• Occasionally mixed involvement of hypothalamus
and pituitary
Clinical features of SOD
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Conjugated jaundice
Neurological features
Variable visual loss
Impaired sense of smell
Endocrine features
Behavioural disturbances eg. autism
Sleep disturbance
MRI SCANS OF SOD PATIENTS
CONTROL
SIBLING 2
SIBLING 1
Management of SOD
• Support from Neurologists and Opthalmologists:
treatment of convulsions
• Mainstay of treatment: endocrine
Endocrine replacement
• Growth hormone: daily subcutaneous injections
• Hydrocortisone: X3 doses daily; adjustment with
illness/stress
• DDAVP: nasal/oral
• Thyroxine
• Ethinyloestradiol/testosterone
Investigations
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MRI scan of brain
Visual evoked responses/electroretinogram
Routine electrolyte measurement
Thyroid function tests
Pituitary function tests:
glucagon/insulin/LHRH/TRH - in tertiary centres
ideally
• Fluid balance
Monitoring
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Evolving - new endocrine features may develop
Monitoring of growth rate at regular intervals
Monitoring through puberty
Regular checks of thyroid function, watch fluid
balance
Long-term outlook
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Short stature
Developmental/intellectual impairment
Fits, hemiparesis etc
Impaired fertility
Visual impairment
Sleep/behavioural difficulties
Obesity
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
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
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)