Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (78 page)

   Trauma (CNS hemorrhage)

   Hypoxia

   Psychosocial deprivation

   Laboratory Findings

Genetic Studies

Children with global developmental delay have a 4% incidence of abnormal cytogenetic studies. A karyotype should be routinely performed on all affected patients even if dysmorphic features are not present. Additional factors that should prompt genetic testing include family history of multiple miscarriages, unexplained infant death, parental consanguinity, or developmental regression or loss of milestones.
^5–7

Chromosomal microarray analysis identifies subtelomeric chromosomal rearrangements, which may be seen in an additional 5% of children with ID. FISH may be used if microarray diagnosis is not available or if a specific telomeric disorder such as cri-du-chat syndrome is suspected.
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Down syndrome (trisomy 21) is the most common form of inherited ID followed by fragile X syndrome, caused by an abnormal expansion mutation of a CGG triplet repeat in the fragile X mental retardation 1 (FRM1) gene. Testing for fragile X mutations should be considered in male and female patients, especially in those with a family history of ID.
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Because Down syndrome often presents with nonspecific global developmental delay in young children, there should be a low threshold for this investigation.
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Metabolic studies
: ID is a clinical feature of some inborn errors of metabolism; these may be identified by newborn screening.

Thyroid screening
: Congenital hypothyroidism may result in ID; thyroid testing is not indicated unless clinical features suggest dysfunction.

Lead screening
: Lead is the most common environmental neurotoxin. At concentrations >10 μg/dL (0.48 μmol/L), it has been associated with cognitive deficits. Children should be screened at 1–2 years of age. Risk factors for increased levels of lead include living in a community where >12% of children have blood lead levels of >10 μg/dL and living in a house built before 1950.
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References

1.  American Psychiatric Association.
Diagnostic and Statistical Manual
, 4th ed. Washington, DC: APA Press; 1994.

2.  Kaufman L, Ayub M, Vincent JB. The genetic basis of non-syndromic intellectual disability: a review.
J Neurodev Disord.
2010;2:182.

3.  Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developments disabilities or congenital anomalies.
Am J Hum Genet.
2010;86:749.

4.  de Ligt J, Willemsen MH, van Bon BW, et al. Diagnostic exome sequencing in persons with severe intellectual disability.
N Engl J Med.
2012;367:1921.

5.  Moeschler JB, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays.
Pediatrics.
2006;117:2304.

6.  Ropers HH. Genetics of intellectual disability.
Curr Opin Genet Dev.
2008;18:241–250.

7.  Shevell M, Ashwal S, Donley D, et al. Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society.
Neurology.
2003;60:367.

8.  Hagerman PJ. The fragile X prevalence paradox.
J Med Genet.
2008;45:498.

9.  American Academy of Pediatrics Committee on Environmental Health. Screening for elevated blood lead levels.
Pediatrics.
1998;101:1072.

DEMENTIA

   Definition

According to the DSM-IV,
¹
dementia is defined by impairment of memory and at least one other cognitive domain such as aphasia, agnosia, apraxia, or executive function. It must also represent a decline in the patient’s prior ability and interfere with daily life.

   Clinical Presentation

The most common form of dementia is Alzheimer disease followed by vascular dementia, frontotemporal dementia, Lewy body disease, Parkinson disease, and progressive supranuclear palsy. These must be differentiated from depression, delirium, and drug or alcohol effects. Disorders that present with no other neurologic symptoms include Alzheimer disease, depression, delirium, and drug effect. Disorders that present with other neurologic symptoms in addition to dementia include neurosyphilis, Huntington disease, hepatic encephalopathy, Creutzfeldt-Jakob disease, Parkinson disease, progressive supranuclear palsy, toxic and alcoholic disorders, endocrine abnormalities, and malignancies.

Reference

1.  American Psychiatric Association.
Diagnostic and Statistical Manual
, 4th ed. Washington, DC: APA Press; 1994.

ALZHEIMER DISEASE

   Definition

Alzheimer disease (AD) is the insidious onset of dementia due to cortical atrophy with accumulation of plaques containing abnormal proteins and fibrillary tangles in the neurons. The dominant abnormal protein is Aβ peptide, a form of amyloid.

   Clinical Presentation