Genetics: B.Sc Nursing II Year

1. NEURAL TUBE DEFECTS
MRS BINCY VARGHESE
ASSOCIATE PROFESSOR
NURSING

2. INTRODUCTION
 Neural tube defects (NTDs) are one of the most common
congenital central nervous system (CNS) malformations.
 Develop between the 3rd and 4th week of pregnancy and
are often caused by folic acid deficiency. The deficiency
results in improper closure of the neural plate in the
embryo, mainly at the caudal or cranial ends.
 The most common type of birth defects and are thought
to have multifactorial etiology.

3.  The diagnosis of NTDs is often established
during pregnancy via Ultrasound and detection of
elevated Alpha-fetoprotein levels.
 Treatment involves prophylactic administration
of antibiotics and swift surgical closure of the defect to
avoid CNS infections. Supplementation with folic acid is an
important preventative measure and should ideally be
initiated 4 weeks prior to conception.

4. DEFINITION
 Neural Tube Defects (NTDs) are a heterogeneous group of
malformations resulting from failure of neural tube closure
between the third and fourth week of embryologic
development.
 Neural tube defects are a group of
congenital malformations of the Brain and Spinal Cord. They
are caused by improper closure of the neural plate in the
embryo resulting in malformations of the Central Nervous
System (CNS), Spine and Cranium.

5. ETIOLOGY
1. Neurulation is defined as the embryonic process that leads to
the ultimate development of the neural tube, the precursor to
the brain and spinal cord. There are two distinct phases of
neurulation.
 In the primary phase (weeks 3–4) the brain and the neural
tube form from the caudal region to the upper sacral level.
 Secondary neurulation (weeks 5–6) completes the distal
sacral and coccygeal regions.
The failure of neurulation at any stage leads to the formation of
a neural tube defect.

6. 2. Multifactorial Genetic and Environmental Factors have been
implicated in the pathogenesis of Neural Tube Defects
(NTDs).
 The most common historical cause of NTDs globally is
folate deficiency in the maternal diet.
 Consanguineous marriages
 Chromosomal abnormalities (Trisomy 13: Patau
syndrome, Trisomy18: Edward’s syndrome, Trisomy 21:
Down’s syndrome) are also associated with NTDs.
 Associated maternal conditions: Diabetes
mellitus, Obesity, Fever/Hyperthermia during first
trimester

7. 3. Single-gene (autosomal recessive) disorders
 Meckel syndrome: Rare, characterised by congenital
anomaly; brain malformation, large polycystic kidneys, cleft
lip/cleft palate, cardiac anomalies.
 Robert syndrome: Rare disorder characterised by growth
delays, malformation of arms and legs, abnormalities of
craniofacial region.
 Jarcho-Levin syndrome: Rare disorder characterised by
defects of spine, ribs.

8. 5. Teratogens
 Valproic acid: Antiepileptic drug
 Carbamazepine: Antiepileptic drug
 Aminopterin: Antineoplastic agent
 Thalidomide: Immunosuppressive agent
 Oral isotretinoin: Vitamin A derivative

9. CLASSIFICATION
NTDs can be classified as “Open” or “Closed” types, based on
embryological considerations and the presence or absence of
exposed neural tissue.
Open NTDs
 Involve multiple aspects of the CNS and are due to failure of
primary neurulation, thus the neural tube fails to
appropriately close along the dorsal midline.
 Neural tissue is completely exposed or covered by a
membrane with associated cerebrospinal fluid (CSF) leakage.

10.  Open NTD’s represent roughly 80% of all NTD’s
 Open NTDs occur when the brain and/or spinal cord are
exposed at birth through a defect in the skull or vertebrae with
the most common being Spina bifida (Meningocele,
Myelomeningocele), Myelocele, Encephalocele and
Anencephaly.

11. Closed NTDs
 Localized and confined to the Spine (the Brain is rarely
affected) and result from a defect in secondary neurulation.
 Neural tissue is not exposed and the defect is fully covered
by epithelium although the skin covering the defect may be
dysplastic (i.e., tuft of hair, dimple, birthmark or other
superficial abnormality).
 Common examples of closed NTDs
are Lipomyelomeningocele, Lipomeningocele and Teth
hered cord.

12. Anatomical Classification of Neural Tube Defects
 Cranial defects
 Spinal defects

13. SPINA BIFIDA
 Spina bifida is a birth defect in which there is incomplete
closing of the spine and the membranes around the spinal
cord during early development in pregnancy.
 The term bifida is from the Latin ”bifidus” or "left in 2
parts." Although the condition has also been referred to as
Myelodysplasia.
 Spina bifida is a treatable spinal cord malformation that
occurs in varying degrees of severity.
 Spina bifida is a variable defect in which the vertebral arch
of the spinal column is either incompletely formed or
absent.

14. Classification
Spina Bifida Cystica
 Spina bifida cystica can occur anywhere along the spinal axis
but most commonly is found in the lumbar region. In this
condition, the spine is bifid and a cyst forms.
 Spina Bifida Cystica can then be broken down into
Meningocele and Myelomeningocele.
Meningocele
 In this form, a single developmental defect allows
the meninges to herniate between the vertebrae. As the
nervous system remains undamaged, individuals with
Meningocele are unlikely to suffer long-term health problems.

15. MENINGOCOELE

16. Myelomeningocele
 Myelomeningocele (MMC) also known as “Meningomyelocele” is
the type of Spina Bifida that often results in the most severe
complications and affects the Meninges and Nerves.
 In individuals with Myelomeningocele, the unfused portion of the
spinal column allows the spinal cord to protrude through an
opening.
 Myelomeningocele occurs in the third week of embryonic
development.

17.  The meningeal membranes that cover the spinal cord also
protrude through the opening, forming a sac enclosing the spinal
elements such as Meninges, Cerebrospinal fluid, and parts of the
spinal cord and nerve roots
 A child born with Myelomeningocele requires specialty care where
Neonatal surgery and Closure can be performed. (Surgery involves
freeing lateral muscles and skin for coverage and attempting to
form a closure).

18. MYELOMENINGOCELE

19. Spina Bifida Occulta
 Occulta is Latin for "hidden". This is the mildest form of Spina
bifida.
 Failure of one or more vertebrae to close completely;
the spinal cord, spinal meninges, and overlying skin remain
intact.
 Usually asymptomatic
 In occulta, the outer part of some of the vertebrae is not
completely closed. The skin at the site of the lesion may be
normal, or it may have some hair growing from it; there may
be a dimple in the skin, or a birthmark.
 Most people are diagnosed incidentally from spinal X-rays.

20. Clinical features of Spina Bifida
In general, infants with Spina Bifida Cystica present with the following:
 Lethargy
 Poor feeding
 Irritability
 Stridor
 Ocular motor incoordination
 Development delay

21. Older children may present with the following:
 Cognitive or behavioral changes
 Decreased strength
 Changes in bowel or bladder function
 Lower cranial nerve dysfunction
 Back pain
 Worsening spinal or lower extremity orthopedic deformities

22. Diagnostic Evaluation
Alpha-Fetoprotein
The AFP level is elevated in 70-75% of cases in which the fetus
has an open spina bifida.
Fetal Ultrasonography
Some Centres use Fetal Ultrasonography as the primary
screening tool for neural tube defects, usually at approximately
18 weeks gestational age. The combination of maternal serum
AFP screening with second-trimester ultrasonographic
screening detects over 90% of neural tube defects from 20
weeks' gestation.

23. Gait Analysis
 Gait analysis has been introduced to evaluate patients
functionally. It is also used to study muscle innervation,
strength, and coordination patterns, which may interfere with
ambulation or with a patient's ability to live independently.
 Gait analysis may serve as a useful preoperative diagnostic

24. CT Scan and MRI
Magnetic resonance imaging (MRI) of the spine and brain is
helpful in neurologic assessment and provides a baseline for
comparison in future investigations, especially in the context of
progressive neurologic deterioration
Radiography
Radiographs of the vertebrae provide information for early
evaluation

25. Management
Bracing
 The goal of bracing is to allow patients to function at the
maximum level permitted by their neurologic lesion and
intelligence. Bracing also ensures a normal developmental
progression, its aim being to enable patients to ambulate and to
participate in appropriate age-related activities.
 In infants aged 9 months and younger, sitting balance and
support may be provided with a standard car seat, elevated 45-
60°. A car seat may be appropriate to maintain mobility with
head and trunk control and to increase upper-extremity strength
in children as old as 18 months.

26.  A Standing Frame may be used for those aged 1-2 years to
diminish the degree of osteoporosis and to limit the contracture
of the hip, knee, and ankle.
 A Parapodium may be helpful for children aged 3-12 years,
allowing them to gain greater experience in standing and in
manipulating work with their upper extremities at a table or
 A Wheelchair can provide mobility and often is used with a
molded ankle-foot orthosis.

27. STANDING FRAME PARAPODIUM

28. ANKLE ORTHOSIS KNEE ANKLE ORTHOSIS
HIP KNEE ANKLE
ORTHOSIS

29. Physical Therapy
 The Therapy programs should be designed to parallel the normal
achievement of gross motor milestones.
 As the child develops, the Therapist monitors joint alignment, muscle
imbalances, contractures, posture, and signs of progressive neurologic
dysfunction.
 The Physical therapist also provides caregivers with instruction in
handling and positioning techniques and recommends orthotic
positioning devices to prevent soft tissue contractures.
 For patients who are not likely to become ambulatory, place emphasis
on developing proficiency in wheelchair skills.
 For patients who are predicted to ambulate, Pregait training should
begin with use of a Parapodium.

30. Recreational Therapy
 Children with Myelomeningocele often experience restricted
and recreational opportunities because of limited mobility and
physical limitations.
 Recreational therapy provides opportunities for participation in
adapted sports and exercise programs, which can result in
long-term interest in personal fitness and health.
Myelomeningocele Closure
 Closure of the Myelomeningocele is performed immediately
birth if external cerebrospinal fluid (CSF) leakage is present. In
the absence of CSF leakage, closure typically occurs within the
first 24-48 hours.

31. Shunting for Hydrocephalus
 Although in a few cases Hydrocephalus arrests spontaneously,
80-90% of children with Myelomeningocele ultimately require
Shunting (Hollow tube placed in Brain/Spine to drain CSF or
redirect it to another location of body where it can be
reabsorbed.
 Ventriculoperitoneal shunting is the preferred modality
(Procedure in which a device is used to drain CSF from Brain to
peritoneal cavity). Alternatives include ventriculoatrial and
ventriculopleural shunting.

32. Orthopaedic Procedures
 Musculoskeletal problems in Myelomeningocele can be
congenital or acquired and often require Orthopedic
intervention.
 Orthopedic surgeries are directed toward functional
improvement as opposed to correction of radiologic findings.
 Spinal deformities are common in Myelomeningocele, and
progressive Kyphosis or Scoliosis may lead to a decline in
functional status and to an increased risk for the
of Decubitus Ulcers and cardiopulmonary compromise.

33.  Spinal Orthotic Devices may serve as a temporizing measure.
 Because muscle imbalance causes progressive, resistant
deformities, the patient with spina bifida must be evaluated
frequently by members of his or her support team. In this way,
they can assess muscle groups, emphasize the need for
balance to prevent deformities

34. ENCEPHALOCELE/ MENINGOENCEPHALOCELE
 Encephalocele is a neural tube defect characterized by sac-like
protrusions of the brain and the membranes that cover it
through openings in the skull.
 These defects are caused by failure of the neural tube to close
completely during fetal development.
 In some cases, cerebrospinal fluid or meninges may also
protrude through this gap. The portion of the brain that sticks
outside the skull is usually covered by skin or a thin membrane
so that the defect resembles a small sac.

35.  Protruding tissue may be located on any part of the head, but
most often affects the occipital area.
 Most Encephaloceles are large and significant birth defects that
are diagnosed before birth. However, in extremely rare cases,
some encephaloceles may be small and go unnoticed.

36. Etiology
 Although the exact cause is unknown, Encephaloceles are
caused by failure of the neural tube to close completely
during fetal development.
 Research has indicated that Teratogens like Trypan blue (a
stain used to color cells blue) and Arsenic may damage
developing fetus and cause Encephaloceles.

37. Clinical Features
 Delays in reaching developmental milestones
 Intellectual disability
 Learning disabilities
 Growth delays
 Seizures

38.  Vision impairment
 Uncoordinated voluntary movements (ataxia)
 Hydrocephalus, a condition in which excess cerebrospinal
fluid in the skull causes pressure on the brain.
 Progressive weakness and loss of strength in the arms and
legs due to increased muscle tone and stiffness (spastic
paraplegia).

39. Diagnostic Evaluation
 USG
 Fetal CT Scan/MRI
Management
 Currently, the only effective treatment for Encephaloceles
reparative surgery, generally performed during infancy.
 Occasionally, shunts are placed to drain excess
cerebrospinal fluid from the brain

40. ANENCEPHALY
Anencephaly is a serious developmental defect of the central
nervous system in which the brain and cranial vault are grossly
malformed. The cerebrum and cerebellum are reduced or absent
but the hindbrain is present.

41. Etiology:
Genetic and environmental factors:
 The specific genes that are most important in NTDs have
yet been identified, although genes involved in folate
metabolism are believed to be important. One such gene,
Methylenetetrahydrofolate reductase (MTHFR), has been
shown to be associated with the risk of NTDs.
 Valproic acid, an anticonvulsant have been shown to
increase the chance of an NTD

42.  Maternal type 1, or Insulin-dependent diabetes mellitus
(IDDM), confers a significant increase in the risk for NTDs
 Maternal hyperthermia has been associated with an
increased risk for NTD; therefore, pregnant women should
avoid hot tubs and other environments that may induce
transient hyperthermia.

43. Clinical features
baby born with anencephaly is usually blind, deaf, unaware
its surroundings and unable to feel pain.
Diagnostic evaluation
 USG
 Maternal AFP level

44. Prognosis
 There is no cure or standard treatment for Anencephaly
and the prognosis for patients is death.
 Infants that are not stillborn will usually die within a few
hours or days after birth from cardiorespiratory arrest

45. ANENCEPHALY

46. CLOSED NTDs

47. Tethered cord syndrome
 Tethered cord syndrome (TCS) refers to a group of
neurological disorders that relate to malformations of the
spinal cord.
 Abnormal stretching of the spinal cord caused by adhesions
or obstructions that tether the cord to the base of the spinal
canal
 Etiology: Tumour, Meningeal adhesions, Lipoma, Cysts
 Symptoms: Back pain, sensory motor deficits, skeletal
deformities(scoliosis), bladder/bowel dysfunction, skin lesions
in lower back
 Diagnosis: CT scan, MRI
 Management: Surgical removal and repair

49. LIPOMYELOMENINGOCOELE
 Lipomyelomeningocele is a condition in which an abnormal
growth of fat (lipo) attaches to the spinal cord (myelo) and its
membranes (meninges).
 Symptoms can include problems with bowel and bladder function,
frequent urinary tract infections, back and leg pain, muscle
weakness or sensory loss in the legs, neuromuscular scoliosis, foot
and leg orthopedic abnormalities, and difficulty walking.
 During surgery for Lipomyelomeningocele, the pediatric
neurosurgeon will free the spinal cord from its attachment to the
lipoma, remove as much of the lipoma as safely possible, and
close the membranes over the spinal cord.
 The goals of the surgery are to prevent deterioration of
neurological function in the future and to preserve or improve
current function.

50. ROLE OF FOLIC ACID
 Maternal malnutrition is an important risk factor for development of
NTD. Studies till date have shown decreased maternal folate levels in
NTD affected pregnancies.
 Periconceptional folic acid supplementation has shown to decrease both
the occurrence and recurrence of NTD, though the exact mechanism for
this protective effect remains unknown.
 Folic acid is a B group vitamin, first isolated from spinach leaf in 1941.
 Folic acid occurs naturally as folates, which are temperature and storage
sensitive and cooking causes significant fall in their concentration.
 Sources rich in folates are liver, green leafy vegetables especially spinach
and broccoli, nuts, egg, cereals, cheese, fruits, yeast, beans etc.

51.  Folic acid is play an important role in cell division and development.
 Folic acid is highly recommended for preventing both occurrence and
recurrence of NTD.
Strategies for improving maternal folate status:
 Dietary modifications: Dietary recommendations of consuming food
high in folate content is beneficial.
 Vitamin supplementation: The second approach is daily folic acid
supplementation to all women in the reproductive age group (18-44
years).

52.  Advise women trying to conceive to take a dose of 400 μg folic acid
daily, starting two months before the planned pregnancy.
 Advise women who have not been supplementing their diet and who
suspect themselves to be pregnant to begin taking 400 μg folic acid
daily and to continue until they are 12 weeks pregnant.
 Counsel pregnant women who previously had a baby with NTD, For
women with Diabetes or who are taking anticonvulsant about the
having a baby being affected. Advise them to take 5 mg Folic acid
and to increase the consumption of Folate in diet.

53. THANK YOU