Congenital malformations

  1. Chiari malformation
    • Part of the brain (usually just cerebellum)  protrudes from the skull into the spinal canal. Occurs on a spectrum.
    • Chiari is classified as 5 types: 0 to IV
    • Type 0: has no brain herniation, just disruption of cerebrospinal fluid flow
    • Type I: most common- just cerebellar tonsils protrude from skull into spinal column
    • > Not a neural tube defect = defect in size/shape foramen magnum. If back of skull is flattened, pressure is put on cerebellum which can cause it to protrude.
    • > May involve malformation of the cervicospinal  junction, can occur if the posterior fossa is small, the foreman magnum is  large, can also be caused by injury or illness.
    • > May be asymptomatic, or present as non-specific neuropathic pain and  neurological symptoms- dizziness, paraesthesia (pins and needles)
    • Complications: SYRINGOMYELIA (fluid cyst), HYDROCEPHALUS (fluid flow issues)
    • Treatment: decompression surgery at base of skull – a small area of bone is removed
    • Type II & III: Probably a different cause than Chiari I, most likely neural tube defects
    • > Chiari II often present with myelomeningocoele, where part of the spinal cord protrudes from the back
    • > Chiari type III may present as encephalocoele where the skull bones are not fused, allowing the hindbrain and meninges to protrude from the skull
    • Types III and IV quite severe- much of brain may protrude from skull
  2. Neural tube defects
    • Chiari II and III, and Spina bifida are all associated with defective neural tube formation
    • Failures in neurulation can leave places where the spinal cord (neural tube) or skull have failed to close correctly.
    • 1st degree neurulation defects: exencephaly, craniorachischisis & spina bifida
    • Exencephaly always leads to anencephaly which is incompatible with life.
    • > cranial neural tube fails to close, so the brain is exposed outside the skull – it then begins to degenerate
    • Exencephaly cannot be treated surgically, always fatal
    • Craniorachischisis = neural tube fails to close. Top part of body doesn’t fuse
    • Spina bifida leads to spinal cord producing from back.
    • > Myelomeningocele (open spina bifida; spina bifida aperta): Like may occur in Chiari II- part of the spinal cord and meninges protrude from a hole in the back, spinal cord may be exposed
    • 2nd degree neurulation defects:
    • > Lipomyelomeningocele: Another sub-type of spina bifida, where a large mass of fatty tissue (lipoma) between the spinal cord and the skin. -> 
    • > Closed spinal lesions: (dysraphic disorders, spina bifida occulta) These may include a splitting, or partial duplication, of the spinal cord.

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    • Treatment: Open lesions leaving the spine exposed lead to further neurodegeneration before birth - in utero surgery is an option to close the lesion
    • > Prognosis for spina bifida patients with a closed lesion, or who have surgery to close a myelomeningocoele lesion, is fairly good – survival to adulthood likely, may have limited mobility in lower body.
    • > Deficiencies in dietary folate, or folate metabolism
    • > Maternal obesity or diabetes- may be genetic factors affecting metabolism, or lifestyle related
    • > Maternal exposure to valproate- a common treatment for epilepsy and some mental health conditions
    • > Unidentified genetic factors- hard to isolate as multifactorial, and low reproductive rate among NTD survivors
  3. Holoprosencephaly
    • Failure of the embryonic forebrain (prosencephalon) to divide into two cerebral hemispheres (not neural tube defects!) Brain divides after neural tube formation.
    • Craniofacial abnormalities associated with HPE range from mild (cleft palate, single median incisor) to moderate (hypotelorism = eyes close together, single nostril) to severe (cyclopia = one large eye associated with nose on forehead, proboscis, agnathia = no jaws). Series/spectrum.
    • > Mild presentation suggests abnormality occurred late in development.
    • > Cleft palate can be caused by other conditions that HPE.
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    • ALOBAR HOLOPROSENCEPHALY: Most severe form - may be accompanied by cyclopia
    • > No separation of brain, and a single large ventricle
    • > Incompatible with life - results in stillbirth or death within first few weeks after birth
    • SEMI-LOBAR HOLOPROSENCEPHALY: Brain hemispheres separated posteriorly but interhemispheric fissure incomplete - may present with hypotelorism
    • > Hind brain separated but not forebrain
    • LOBAR HOLOPROSENCEPHALY: Two brain ventricles but frontal lobes remain fused 50% of cases survive > 12 months.
    • > Prospect of survival depends on other deformities, and genetic cause.
    • Causes: many genes involved in division of hemispheres
    • > Chromosomal abnormalities
    • > Mutations in genes involved in key developmental pathways
    • > Environmental factors- retinoic acid
    • CHROMOSOMAL ABNORMALITIES: Trisomy 13, trisomy 18 and triploidy may cause 24-45% of HPE cases, and also cause a range of other severe developmental abnormalities incompatible with life. Chromosome 18 prone to abnormalities.
  4. Microcephaly
    • Small head (microencephaly = small brain)
    • Presents as smaller head with smaller brain, particularly the cortex BUT brain structure is normal
    • May have mild to moderate learning disabilities, motor problems, speech problems or seizures
    • Prognosis: generally good, survival to adulthood
    • Causes - Genetic: mutation in one of the microcephalin genes such as MCPH1
    • > The exact function of the microcephalin protein is unknown but it is expressed during brain development
    • > autosomal recessive trait - must inherit both copies
    • Causes - Radiation: definitely caused by radiation. 20-50% of babies from survivors of Hiroshima and Nagasaki had MCE
    • Causes - Infection: Zika virus (4.7% of pregnancies with confirmed Zika infection resulted in birth defects), Toxoplasma, Cytomegalovirus (linked to range of foetal abnormalities), Rubella and Varicella (chicken pox)
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Congenital malformations
Congenital malformations of the brain and spinal cord