Embryopathies. Malformations of central nervous system and limbs.
Congenital abnormalities of the CNS can be divided into developmental malformations and disruptions.
Developmental malformations are the result of flawed brain development. This may be genetic or environmental. Disruptions result from destruction of normally developed (or developing) brain and are environmental or intrinsic (e.g. fetal infection). Holoprosencephaly, where the forebrain is not divided into hemispheres, is an example of a malformation while hydranencephaly, where there are fluid filled sacs reducing brain mass is a disruption.
The CNS is particularly sensitive to teratogenic factors, and external environmental factors will often result in CNS damage before other forms of congenital malformation.
Common neurological embryopathy occur within the neural tube, which develops from the neural plate at around the 25-26 day. For instance, defective closing of the neural tube results in brain defects or spina bifida, depending on if it is the top or bottom that fails to close.
Open spina bifida (myelomeningocele): the spinal cord and meninges protrude in a CSF-filled sac through the unclosed vertebral arches.
Image: “Spina-bifida” by Centers for Disease Control and Prevention, Public domain, via Wikimedia Commons.
Remember: failure at the cranial end gives anencephaly; at the caudal end it gives spina bifida, from mild to severe: spina bifida occulta (bony defect only), meningocele (meninges herniate), myelomeningocele (meninges and cord). Folic acid before conception and in early pregnancy lowers the risk; open defects raise alpha-fetoprotein in maternal serum and amniotic fluid.
The main disorders of cortical development include:
- Microcephaly - abnormally small head circumference
- Megalencephaly - increased brain size (assoc with learning difficulties)
- Lissencephaly - complete absence of gyri (smooth brain)
- Heterotopias - abnormal neural collections in subependymal region
- Polymicrogyria - increased number of abnormal ridges and folds (gyri)
- Disorders of cortical organisation
Malformation of the limb involve missing, incomplete, supernumerary or abnormally developed limbs that are present at birth. Most are a result of intrauterine growth inhibitions, or disruptions to embryonic tissues, some are caused by teratogenic agents such as thalidomide. Limb deformities can be longitudinal or transverse:
- Longitudinal
- Specific mal developments where an element of a limb is missing.
- For instance, deficiency of the radius is a common upper limb deficiency and hypoplasia of the fibula is a common lower limb deficiency
- Most are associated with other syndromes
- Transverse
- All elements beyond a certain level are absent, and the limb resembles an amputation stump
- Amniotic bands are a common cause, often not associated with other symptoms.