Congential Pathology (and assessment for developmental disorders) Flashcards
What is considered normal development?
• Individual who grows and matures on an expected path and achieves developmental milestones appropriately
What is considered abnormal development?
• Individual who is unable to achieve developmental milestones as expected compared to those of similar age
When is a developmental milestone considered delayed?
- When that individual is 2 standard deviations below the mean
- They are outside of 95.5% of the population
What is the proper term for mental retardation?
• The phenotype is better known as intellectual disability
Is a developmental disability the same as a developmental delay?
• No, they are not the same
How do you label something a developmental delay?
- From the journal of pediatric psychology
- 2 SD below the mean for a child’s chronological age
- Developmental quotient = (developmental age)/(chronological age)
- If over 85, give reassurance
- Btw. 70 - 85 close monitoring
- Below 70 - refer to a specialist in development
What are the developmental domains?
- Gross motor
- Fine motor
- Language
- Cognitive
- Social
- Each are considered a different area in which you can experience a delay or problem
What are the 4 parts of the clinical approach to developmental problems?
• History ○ Milestones reached • Parent report questionnaires ○ Ages and stages (ASQ) • Physical examination • Formal evaluation ○ Child development team
What is the cost to the family for screening tests for developmental delays?
- Depends on the service
- The most expensive is 115 dollars for 100 forms and 1 kit (denverii)
- 75 dollars - child development inventories - forms to start then 1 dollar per screen
Do the screens that you pay for actually work?
- Each service has different number of items
- Max specificity is 96%
- Max sensitivity is 80%
- Limited by language available
What are the criteria for labeling an intellectual disability?
• Must be present from childhood • IQ must be 2 SD below the mean (less than 70-75) • Significant limitations in more than 2 adaptive skill areas ○ Communication ○ Self care ○ Home living ○ Social skills ○ Community use ○ Self direction ○ Health and safety ○ Functional academics ○ Leisure and work
What is the age threshold for reliably measured IQ?
• 5 years. Can’t be reliably done before that
What is mild Intellectual disability?
• IQ of 70-50, 85% of ID population
What is moderate Intellectual disability?
• IQ of 50-35, 10% of ID population
What is severe Intellectual disability?
• IQ of 35-20, 10% of ID population
What is profound Intellectual disability?
• IQ less than 20, 1% of ID population
What’s up with cerebral palsy?
- Acquired disease
- Non-progressive
- Motor impairment
- Onset in utero, infancy or early development
- Spastic (70-80%) vs. athetoid/dysckinetic (20%) vs. ataxic (10%)
What’s up with Autism?
• Social interaction problems
• Social communication problems
• Restricted repertoire of interests, behaviors and activities
• Delays or abnormal functioning in at least one of the following with onset prior to age 3:
○ Social interaction
○ Language as used in social communications
○ Symbolic (20 months) or imaginative play (2 years)
What is meant by the umbrella term: developmental disability?
• Severe, chronic disability of an individual 5 years of age or older ○ Attributable to a mental or physical impairment ○ Manifested before the person is 22 years old ○ Likely to continue indefinitely • Substantial functional limitations: ○ Self care ○ Receptive and expressive language ○ Learning ○ Mobility ○ Self-direction ○ Capacity for independent living ○ Economic self-sufficiency
What’s the flow chart for managing a developmental delay?
- Routine well child check
- Parental concern is expressed
- Screening
- DQ less than 70, refer
- Refer to neurologist or child development specialist
- Confirms DD and works up testing for etiology and advises treatment
What are the three categories given for etiology of developmental disorders?
- Congenital
- Genetic/heritable
- acquired
If a child acquires a disease intrauterine, what category does that fall in?
- Congenital
- Infections - CMV, toxoplasmosis
- Toxic - fetal alcohol
- Stroke
- Unknown - congenital hydrocephalus
What’s up with Fragile X?
• Clinical features ○ Long jaw ○ High forehead ○ Large/protuberant ears ○ Hyperextensible joints ○ Soft/velvety palmar skin ○ Enlarged testes ○ Initially shy with poor eye contact then friendly and verbose ○ Family history of MR • Mutation in FMR1 gene from CGG tirnucleotide repeat
What’s up with Rett Syndrome?
• Clinical features ○ Microcephaly ○ Ataxia ○ Autistic features ○ Sterotypical hand movements ○ Hyperventilation ○ Seizures • X-linked MECP2 gene
What’s up with angelman syndrome?
• Clinical features ○ Wide mouth and prominent chin ○ Seizures ○ Microcephaly ○ Nonverbal ○ Happy demeanor/frequent smiling ○ Ataxia ○ Hand flapping • Chromosome 15q11-13 methylation/deletion
Why should lead poisoning be on your differential for DD?
• 10% of children with DD and presence of risk factors have eleveted blood lead levels
What does the term congenital mean?
- Present at birth
* Can be genetic in origin but many are not
What different classes of congenital disorders did we discuss?
- Neural tube defects
- Telencephalic development disorders
- Cerebellar development disorders
- Disorders of neuronal proliferation and migration
- Destructive lesions that interfere with normal development
When in time does a problem result in myelomeningocele, ethmocephaly and anencephaly?
• In the 3rd week, with neuroschisis
Of all the neural development malformation cases, what percentage are purely genetic?
- Only 8% are genetic
- 12% are due to extrinsic factors affecting the mother and fetus
- 60% of cases are unknown in origin or etiology
When does the cerebellum develop?
- The bulk of it is in the second half of pregnancy
- There is quite a bit of postnatal cerebellar growth though
- External granular layer persists until the end of the second postnatal year, supplying the grounds for more development
Relative to birth, what is the extent of cerebral myelination?
- The cortex continues to grow in thickness until the end of the 2nd postnatal year
- Most of that is myelin in the cerebral hemisphere
- Right at birth it’s tough to pick out grey vs. white matter
- Between birth and 6 mo, brain weight nearly doubles. But myelination still happens into 2nd decade
What are the vocabulary terms for Neural Tube Defects?
- Rachischisis
* Dysraphism
What, in general, causes neural tube defects?
- Etiology is still pretty unknown
- The process is a failure of the neurectoderm to form a complete, closed tube during primary neurulation
- Could also be from disordered differentiation of the caudal cell mass into the conus medullaris and filum terminale during secondary neurulation
What’s up with anencephaly?
- NTD defect
- Failure of rostral neuropore to close
- Forebrain neuroectoderm fails to separate from the cutaneous ectoderm
- Red area cerebrovasculosa is seen where the calvarium should have developed
What’s up with encephalocele?
- NTD defect
- Defect in the skull with protrusion of leptomeninges +/- brain
- There is an epidermal covering over the cranial neural tube closure defect (thus different than anencephaly)
What’s up with myelomeningocele?
- NTD defect
- Failure of posterior neuropore to close
- 80% are in the lumbar area, which is the last one to close
- Neural placode without epidermal covering
- CSF leak
What’s up with meningocele?
- NTD defect
* Skin covered (so not leaking) CSF-filled mass that is continuous with the CSF in spinal canal
What’s up with lipomyelocele/lipomyelomeningocele?
- NTD defect
- Lipoma extends from the subcutaneous tissues to the dorsal aspect of the spinal cord
- The lipoma tethers the cord inferiorly
- Process reflects a premature separation of the cutaneous ectoderm during the process of neurulation that allows mesenchyme to enter the unclosed neural tube and differentiate into fat
What’s up with dorsal dermal sinus tract?
- NTD defect
- Ectoderm-lined tracts that can transgress the dura and allow communication between the skin and CSF
- Can also cause tethering of spinal cord
- Can be associated with an intradural dermoid cyst or epidermoid
What are the physcial exam findings that might indicate a NTD?
- “underlying spinal dysraphism”
- Usually situated in or near the midline
- Usually lumbosacral region
- Dermal dimple
- Hairy patch of skin
- Lipoma or other midline visible mass
- Dermal sinus
- Capillary hemangioma
What’s up with spina bifida occulta?
- At the L5-S1 level this is a common incidental finding on radiographs (both children and adult)
- Not usually associated with sypmotoms or signs
What is meant by spinal cord “tethering”?
- Conus medullaris is usually L3 at birth but ascends into adulthood
- Many of the NTD defects will effectively resist that ascension because there is a tissue connection that tethers the cord
- Can lead to spinal cord damage
- Often first signs are hyperreflexia and spasticity as well as urinary incontenance
Hydromyelia means what?
- Accumulation of CSF within the central canal
- Some obstruction does not allow full communication of ventricles with sub-arachnoid space
- Chiari type I malformation can cause this
Syringomyelia means what?
- Formation of a CSF-filled cyst that breaks out of the central canal and dissects into the substance of the cord
- Usually because of some type of obstruction that doesn’t allow for communication of ventricles with sub-arachnoid space
- Chiari type I malformation can cause this
What is the Chiari Type I malformation?
• Finding of cerebellar tonsils that are elongated and pushed down through the foramen magnum, blocking the flow of CSF
* worry about hydromyelia and syringomyelia and hydrocephalus (4th ventricle problems)
Chiari type I malformation may be a problem with what embryonic layer?
- Mesodermal disorder
- May be a problem more with the formation of a small overcrowded posterior cranial fossa
- This disease is NOT associated with myelomeningocele
What malformation is very often seen in conjunction with a thoraco-lumbar meylomeningocele?
• Chiari type II malformation
What is characteristic of a Chiari type II malformation?
- Elongation of the cerebellar vermis through the foramen magnum which blocks CSF flow
- Abnormalities of brainstem including beaking of the midbrain tectal plate and a z-kink in the medulla
- Abnormalities of the dural venous sinus including a low-lying confluence of sinuses and osseous abnormalities of the skull
What physical event seems to result in chiari II malformation?
- Leakage of the CSF from the primitive ventricular system leads to a failure of the ventricles to increase in size and volume
- Both downward and upward herniation of the small cerebellum will cause the ventricular dilation
- Also the posterior fossa does not develop to its full size and the neuroblasts do not migrate outward at a normal rate
- Essentiall the whole messed up posterior fossa due to the leakage of CSF
What causes holoprosencephaly?
- The improper cleavage and thus development of the telencephalon
- The prosencephalon normally forms the two lateral ventricles and the third one (diencephalic vesicle) but it can be completely or partially cleved
- Two cerebral hemispheres do not divide properly
- During the 5th week of fetal life
How many types of holoprosencephaly are there?
- Three types classified by the degree of division
- Alobar (arhinencephaly)
- Semilobar
- Lobar
What’s up with alobar holoprosencephaly?
- Arhinencephaly
- No evidence of division of cerebral cortex
- Single forebrain with a single ventricle instead of two cerebral hemispheres with lateral ventricles
- Fusion of thalami
- Rudimentary corpus callosum
What’s up with semilobar holoprosencephaly?
- There is only partial cleavage with the cerebal hemispheres fused at the frontal region only
- The brain has a horseshow appearance single central ventricle
- Variable degrees of fusion of the thalami and absent olfactory bulbs and corpus callosum
- Single ventricle with rudimentary occipital horns
What’s up with lobar holoprosencephaly?
• Cerebral hemispheres are separated anteriorly and posteriorly with some degree of fusion of structures
What are more obvious clues of holoprosencephaly?
- Facial and ocular development are linked so there are deformities of the face and eyes
- Cebocephaly - single nostril
- Cyclopia - fused or nearly fused orbits with supra-orbital proboscis
- Ethmocephaly - high midline proboscis
- Arhinia - no fetal nose
- Coloboma of iris and retina, microphthalamus, premaxillary agenesis
- Midline facial clefts
What’s the most common cerebellar developmental disorder?
- Dandy-Walker malformation
- Partial or complete absence of formation of the cerebellar vermis
- Cystic dilation of the fourth ventricle
- Upward displacement of the tentorium (dura that separates the cerebrum from cerebellum)
- MAY have hydrocephalus
- Sporadic, not NTD, not genetic, not linked to folate, but maybe to cis-retinoic acid and homeobox genes
Vascular-ischemic destructive events in late pregnancy can cause what problems?
- Porencephaly - large unilateral holes
- Schizencephaly - bilateral symmetrical holes
- Hydrancencephaly - destruction of one entire hemisphere
What’s the breakdown of types of stroke in children?
- 55% are ischemic
- 45% are hemorrhagic
- Most causes of stroke in childhood are genetic or malformative
Back before C-section and babies needed to come out of a too small hole or were breech, what was the result sometimes?
- A watershed stroke because of stretching carotids and vascular insufficiency
- The infants brain grows around the infarct and forms a mushroom shaped gyrus
- Ulegyria - condtion of mushroom shaped gyri
Cerebral palsy is what?
- An umbrella term for a group of motor-sensory cerebral disorders manifested since early childhood and attributed to various etiologies
- Movement disorders like athetosis (involuntary writhing movement) and dystonia (opposing muscles contracting uncontrolled, painful and fixed postures)
- Epilepsy, cognitive impairment, visual and hearing problems
Why are SEH vascular problems so harsh in the fetus before 32-34 weeks gestation?
- Subependymal hemmorages - seh
- Hemmorrhage in the vulnerable germinal matrix where all the growth plate for neurons and glia are
- Germinal matrix is highly vascular, highly cellular and if it’s messed up then neuronal development is super messed up
What’s meant by GMH in pediatrics?
- Germinal matrix hemorrhages
- Same thing as subependymal hemorrhages
- These cause lots of Cerebral Palsy
- Graded on a 1-4 scale by the papile method
- Grade IV show back dissection of the large hemorrhage into the surrounding cerebral white matter
- Grade I is a localized hemorrhage
What are the risk factors associated with GMH generation?
- Gestational age
- Immature fetal lungs resulting in hyaline membrane disease
- Hypercapnia
- Low birth weight under 1500gm
- Acidosis
- Coagulation defects
What is the final site of closure that, if it fails, will result in anencephaly?
- Commissural plate
- Anterior neuropore does not fuse/close
- Immediately anterior to the lamina terminalis at the site of the future anterior commissure
