Childhood Disorders



  • Nonscientific term describing permanent, nonprogressive neurologic motor system impairment resulting from CNS injuries of the immature brain (occur pre- or peri-natally, infancy, or early childhood); .2% incidence
    • Can be associated with prematurity (especially as smaller premature infants continue to survive) and low birth weight; however, specific causes have not yet been identified
    • Less than 15% result from a preventable obstetric injury
    • CP is not a single entity and the etiology of its various presentations is not the same
    • It is a general term which doesn’t tell the severity/nature of the disorder (same as “learning disability”)
  • Nonprogressive but not unchanging disorder of movement and posture; changes occur as the nervous system matures (e.g., a baby may be hypotonic but later b/c spastic or rigid; all CP has an early hypotonic phase) – in some instances there is a gradual improvement, but others reach a plateau; many require bracing and surgery
  • Two most common varieties:
    • Spastic paresis (70%)
      • Combination of spasticity (causes slow clumsy movements; usually accompanied by hyperactive deep tendon reflexes, clonus, and Babinski signs) and paresis
      • Affected limbs have growth arrest
      • Results from necrotic areas in the white matter around the ventricles (periventricular leukomalacia) – most closely related to prematurity
    • Extrapyramidal (“dyskinetic”) CP (choreoathetosis) (15%)
      • Characterized by choreoathetosis (involuntary writhing of face, tongue, hands, and feet sometimes overridden by jerking movements of trunk, arms, and legs)
      • Involvement of larynx, pharynx, and diaphragm may lead to severe dysarthria
      • Usually produced by combo of low birth weight, anoxia, and kernicterus that damages basal ganglia and auditory pathways
      • Lowest incidence of epilepsy and MR
  • 15% of the cases are “mixed”
  • Associated complications/disabilities:
    • MR; cognitive dysfxn
    • Epilepsy (generally associated with more global impairment)
    • Vision/hearing impairments
    • LD
    • Language disorders
    • Psychological problems
    • Pseudobulbar palsy
    • Hyperactivity
  • Sometimes the child’s most disabling problems are associated cognitive difficulties (though 50% have normal intelligence); visual-perceptual problems, speech and hearing impairments may influence learning


Result from defective embryologic development of CNS during 3rd and 4th weeks gestation



  • Vault of skull absent; brain usually represented by a vascular mass; face grossly abnormal
  • May be due to severe trauma, radiation, infection; abnormal embryonic development between day 18 and week 4 gestation
  • Incompatible with life (die within minutes/hours of birth); interestingly, organs are ideal for transplants


  • Skin-covered brain, meninges, or CSF protrudes through skull defect
  • Results from incomplete closure of mesodermal layers over the upper neural tube
  • Cranium bifida = fusion defects of the skull
  • Encephalocele = myelomeningoceles or meningoceles that occur on the skull
  • Many possible behavioral complications arising from associated hydrocephalus – e.g., MR, ataxia, CP, and epilepsy


  • Posterior portion of upper neural tube fails to develop; born with rudimentary posterior brain structures
  • Cerebellum/medulla fail to develop past early embryonic stage; fourth ventricle grows into a large cyst
  • Associated with hydrocephalus, agenesis of CC, craniofacial deformities, Klippel-Feil syndrome, DeLange syndrome, macrocephaly, MR
  • Frequent severe psychomotor retardation


  • Congenital deformation of the brain stem and cerebellum
  • Some combination of medulla and cerebellum are displaced downward through foramen magnum; aqueductal stenosis; overlying skull and cervical spine defects
  • May be due to traction caused by myelomeningocele or hydrocephalus; may be a dysgenesis of the brainstem
  • Associated with congenital hydrocephalus, spina bifida, myelomeningocele, severe psychomotor retardation; in “asymptomatic” cases, adults may present with headache, bulbar palsy, and neck pain



  • Asymptomatic spinal lesion discovered incidentally; possibly 20% of population
  • Abnormal fusion of spinal lumbar vertebra
  • Often asymptomatic; may be associated with lipoma, congenital dermal sinuses, dimples
  • No documented cognitive deficits


  • Spinal defect that includes a cystic-like sac (meningomyelocele), which may or may not contain the spinal cord; 1-2: 1,000 live birth incidence
  • Meningocele – meninges & skin protrude through lumbosacral spine defect to form CSF-filled bulge (no spinal cord) = good prognosis, though may cause gait impairment, kidney and bladder problems, loss of tissue barriers that protect CNS
  • Myelomeningocele or meningomyelocele (much more common) – tangle of rudimentary spinal cord, lumbar and sacral nerve roots, meninges protruding into sac = 80-90% chance of developing hydrocephalus and have many other problems (incl. meningitis, Arnold-Chiari)
    • Clinical deficits worsen during childhood and during growth spurts despite early surgical intervention
    • Most all are MR and paraplegic
    • May be due to autosomal recessive genetic abnormality; radiation, folic acid deficiency, toxins, and AEDs also implicated



  • Cerebral hemispheres replaced by cystic sacs containing CSF
  • May be due to vascular occlusion causing necrosis
  • May initially look like hydrocephalus; eye movement disturbances, feeding problems, hyponatremia
  • Incompatible with life


  • Large cystic lesion develops, usually bilateral
  • Disturbed cortical development between month 5-7 gestation; may be due to severe trauma, vascular occlusion, infection
  • May be asymptomatic; often associated with MR, epilepsy, other malformations (e.g., polymicrogyria)
  • Gyri often form radial patterns around cyst


  • Obstruction of the aqueduct and CSF circulation
  • Evidence for familial transmission
  • Often insidious onset of symptoms associated with hydrocephalus
  • Shunted children may have learning/behavioral problems; nonverbal IQ worse than VIQ

NEUROMIGRATIONAL DISORDERS (NMD’S) (malformations of the cerebral cortex et al.)

Disorders due to errors in the development of the brain (cells migrating incorrectly)

LISSENCEPHALY (AGYRIA – absent gyri, smooth cortical surface/PACHYGYRIA – few, course gyri)

  • Disorders of cell migration; arrest of migration of neuroblasts from periventricular matrix to cortex
  • Characteristic facial appearance: prominent forehead, short nose, protuberant upper lip, and small jaw
  • Associated with agenesis of CC, micrencephaly, epilepsy, severe growth and developmental retardation, decreased spontaneous activity; early death due to intercurrent disease common
  • May have difficulty swallowing or eating; may respond minimally to visual or auditory stimuli
  • Seizures


  • Development of many small gyri
  • Possibly due to focal necrosis during neuroblast migration between 5-6 months gestation
  • Associated with LD (dyslexia), severe MR, epilepsy; may be asymptomatic

FOCAL DYSPLASIA (heterotopias)

  • Focal abnormalities of the cortical cytoarchitecture; areas of disordered layering and displaced cells
  • Disruption of neuroblast migration
  • Reported in pts with epilepsy and LD


  • Refers to a large head (circumference > 2 SD’s above the mean)
  • Involves increased numbers of neurons and glia.
  • Typically mentally retarded, but may be mild


  • Characterized by clefts in parasylvian region and in precentral/postcentral gyri of one or both hemispheres
  • Often accompanied by hydrocephalus, mental retardation and significant motor handicap


  • Failure (complete or partial) of CC to develop; <.7% incidence
  • Evidence for familial transmission
  • Interruption of normal embryogenesis at 12-22 weeks gestation
  • Increased incidence in schizophrenics; and is seen in association with spina bifida, facial and ocular deformities, micrencephaly, megalencephaly, hydrocephalus, Dandy-walker Syndrome and Leigh’s syndrome; epilepsy and MR may occur; may see EEG abnormalities
  • Can follow intrauterine exposure to toxins (e.g., FAS)
  • Associated with specific, but different patterns of neuropsychological deficits including:
    • Visual spatial deficits
    • Impaired syntactic ability (comprehending, producing or repeating complex sentences)


  • Embryologic defects in the ectoderm
  • Often include abnormalities of other ectoderm and nonectoderm organs
  • Most are inherited in an autosomal dominant pattern
  • Usually stable through adulthood, though cerebral lesions may undergo malignant transformation


  • Smooth and firm nodules on malar surface of face (adenoma sebaceum or facial angiofibromas) don’t appear until adolescence
  • Infancy and childhood – subtle hypopigmented areas on skin, scaly lesions on trunk (shagreen patches), and periungual fibromas of the fingers
  • Classic Triad (occurs in minority): epilepsy (usually intractable), MR, hypopigmented areas or adenoma sebaceum; includes speech and language delays
  • Some eventually decline to the point of dementia; some have autistic features – overall, highly variable (partly attributable to location of abnormal gene – chromosome 9 or 16)
  • CNS correlate of skin lesions are cerebral tubers (“potato-like brain nodules”) – cause epilepsy and cognitive impairment; may become malignant; may develop retinal, renal, cardiac tumors


  • NF Type I (aka von Recklinghausen’s disease, or “peripheral type” NF)
    • Inherited on chromosome 17 in autosomal dominant pattern; though often (upto 50%) arises spontaneously
    • Classic Triad: café au lait spots, neurofibromas (emerge along peripheral nerves; may reach grotesque proportions), Lisch nodules (multiple, asymptomatic, macroscopic, melanocytic hamartomas on the iris – pathognomonic) (brain hamaratomas often observed on imaging)
    • Also involves intracerebral tumors (e.g., astrocytomas, optic nerve gliomas)
    • High association with ADHD and LD (1/3-2/3 of affected children); lower IQ
  • NF Type II (aka familial acoustic neuroma, or “central type” NF)
    • Bilateral acoustic neuromas (hallmark) that impair hearing until deaf
    • Inherited on chromosome 22 in autosomal dominant pattern
    • May manifest meningiomas; mental impairment only if they compress critical brain region

STURGE-WEBER SYNDROME (aka encephalo-trigeminal angiomatosis)

  • Facial (port wine stain in region of trigeminal nerve) and cerebrovascular malformations
  • NO known genetic basis
  • Cerebral component – calcified vascular region accompanied by atrophy in one hemisphere
  • Tend to have MR, LD, behavioral disturbances, refractory epilepsy; may also have focal physical deficits depending on site of lesion
  • Presence of seizures associated with much poorer prognosis


  • Inherited in a recessive pattern; abnormality on chromosome 11 – interferes with DNA repair
  • Consistently associated with immunodeficiency (little or no IgA or IgE)
  • First manifestations – chronic sinus and respiratory tract infections; later, lymphomas and neoplasms
  • Neurologic manifestations at age 3-5: progressive ataxic gait (due to degeneration of cerebellar vermis)
  • Develop cognitive impairments
  • Cutaneous component – small dilated vessels (telangiectasia) on conjunctiva, nose bridge, and cheeks


Remain stable post-puberty; do not cause signs of white matter disease (leukodystrophies), do not cause metabolic storage disease

Genetic imprinting – when the same autosomal dominant abnormality produces different syndromes depending on whether it is transmitted from mom or dad (as in Prader-Willi and Angelman syndromes)



  • 1:600 births
  • Trisomy 21 (3 chromosomes or parts of chromosomes instead of two – the entire chromosome 21 is not required; it is possible that the variation in the amount of chromosome is related to the variability of the cognitive deficits)
  • Risk increases with maternal age
  • Affects organ systems (e.g., may have increased risk for congenital heart defect); alters antibody rxn to vaccine; increased risk for otitis media; increased risk of leukemia and seizures
  • Alzheimer’s is invariably found over the age of 40 (increased risk from age 10 on! 15% of those from 10 – 20; 36% in those 21 – 30 yrs; 100% if over 30)
  • Mean IQ is approximately 44.3; range from mild to moderate MR
  • Visuospatial abilities are generally preserved and language is impaired; motor delays; intact social skills
  • Difficulty processing sequential information

PRADER-WILLI SYNDROME (chromosome 15 – get this disorder if passed from father “Prader-Willi is passed in a paternal pattern”) ~ although some cases are sporadic

  • Due to a deletion in a chromosome
  • Obese, voracious appetites (hyperphagia); poorly controlled food-seeking behavior (will steal food from classmates, rummage through garbage, etc.) and they gain wait at an accelerated rate (doesn’t appear until the preschool years; prior to this they are pleasant and not obese); short stature, hypogonadism
  • Outbursts of aggressive, angry behaviors; some repetitive, compulsive skin picking
  • Mental retardation, obsessive-compulsive personality, decreased sensitivity to pain
  • Major language production deficits (affect articulation)

ANGELMAN SYNDROME (“Happy Puppet”) (chromosome 15 – get this disorder if passed from mother)

  • Rare (also due to a deletion in chromosome)
  • Associated with motor and severe mental retardation, microcephaly, epilepsy
  • Stereotyped involuntary and jerky-ataxic voluntary movements, smiling face, paroxysms of unprovoked laughter
  • Appear to be normal at birth but rapidly drift off developmental course
  • Speech is limited to a few words at best but can communicate with gesture
  • Hyperactive
  • Girls are sometimes misdiagnosed as Rett’s syndrome (MR, microcephaly, involuntary movements); others may be diagnosed as autistic

WILLIAMS SYNDROME (chromosome 7)

  • Minute deletion on 7 which disrupts elastic properties of arteries, root of aorta, skin, and other organs
  • Characteristic elfin face; facial features become more prominent with age
  • No gross neurological abnormalities, though motor delays and fine and gross motor clumsiness
  • Mild to moderate MR; impaired reading and writing; visuospatial deficits; difficulty w/nonverbal tasks
  • Inexplicably, extraordinary talents in music (gifted) and verbal fluency (though devoid of substance)

PKU (chromosome 12)

  • Amino acid metabolism disorder; autosomal recessive
  • Aminoacidurias (another aminoacidurias is maple syrup urine disorder which can also be treated with diet)
  • Prevents normal metabolism of phenylalanine to tyrosine; prevents normal synthesis of dopamine, subsequent neurotransmitters, and melanin; phenylketones are excreted in urine
  • Untreated leads to severe MR, decreased attention, lack of responsiveness to environmental stimuli, seizures, spasticity, hyperactive reflexes, tremors, “psychiatric illness”
  • Treatment diet (no phenylalanine) leads to short stature and weight, anemia, and hypoglycemia
  • Even when treated, tend to show executive deficits, ADHD symptoms and below average IQ


x-linked disorders – may be rare in females if it is a recessive trait unless there is a mutation in the other X (or if they both contain the disorder); if it is dominant it will be expressed in both genders


  • 2nd most common form of mental retardation (second to Down Syndrome); most common inherited form (responsible for as much as 10% of all MR cases)
  • Trinucleotide (CGG) repeat in defective gene; people with >200 repeats are invariably affected; size of repeat increases with successive generations which results in earlier onset (“anticipation”) and more pronounced symptoms
  • Fragile-x males (1:1500)
    • Head circumference and weight > peers; by adulthood only the head remains large; elongated face; enlarged testicles
    • IQ ranges from normal to profoundly mentally retarded (70% moderate to severe MR; 20% seemingly normal); studies suggest IQ declines b/t childhood and adulthood
    • Tend to plateau with regard to their ability to learn more complex and abstract information, typically during early puberty
    • Dysfluent, apraxic speech, echolalia, palilalia and cluttering are characteristic; receptive language relatively preserved
    • Frequent behavioral abnormalities, including ADHD; also, LD, mood disorder, repetitive purposeless involuntary movements, autism, PDD (15%)
  • Fragile-x females (1:3000)
    • In contrast to other sex-linked disorders, 1/3 of female carriers express some of its characteristics
    • Often lack dysmorphic features seen in males
    • Specific frontal lobe deficits have been seen
    • No evidence of right hemispheric impairment, dyslexia or short-term verbal memory deficit; but another book states there is!! (e.g., problems with spatial skills and math)
    • Attention deficits, distractibility, shyness, impaired organizational skills and difficulty with transitions
    • IQ – 80’s to 100; often below 85
    • Behavioral abnormalities (see above) less common than in boys


  • Females only; abnormality assumed lethal in males
  • Onset begins after about 6 months of normal development, then regress in all areas of psychomotor development over several years until no language, walking, cognitive capacity, etc.
    • profound MR
  • Two virtually unique physical characteristics: stereotypies (often incessant hand clapping and wringing) and acquired microcephaly (after 6 months of normal growth)
  • 50% have seizures
  • Shares features with autism, but also have progressive loss of motor ability and develop microcephaly
  • Of note: Rett’s, Angelman’s and Fragile X should all be differentials for autism


  • Seen in males
  • Tall stature, but “eunuchoid” after puberty (often diagnosed after puberty, sometimes in context of fertility workup – sterile, testicular dysgenesis)
  • In general, IQ below average (80-90); 25% have some degree of MR (usually mild)
  • Tend to have dyslexia and LD
  • Some describe as “passive” or with decreased libido


  • Seen in females (often associated with miscarriage; only 1% of affected fetuses are born)
  • Due to various genetic defects; missing X chromosome (XO), some are XO/XX mosaics
  • Dysmorphic features – small stature, poorly developed secondary sex characteristics, sexual dysfxn in puberty/adulthood, webbed neck, broad chest, deformed bend in forearm, low set hairlines, low set ears and atypical facies; usually no neurological abnormalities
  • Do not have a consistent npsych profile; considerable heterogeneity in the profile and severity; MR is rare or mild (20% have mild)
  • Verbal strengths contrast with nonverbal; visuospatial deficits are common (PIQ<VIQ is usual; but 10 – 20% show the opposite); typically show a pattern consistent with NVLD
  • Math difficulty is common; social deficits and impaired facial recognition; at risk for NVLD; some say striking deficits in perception of form and space; may see LD and ADD
  • May have anxiety/depression


  • Extremely tall; severe acne persists beyond adolescence
  • Cerebral development may include migrational abnormalities and maturational delays
  • Tendency toward higher activity levels, more negative mood and temper tantrums have been noted
  • Historically, research on “supermales” conducted in prisons, and indicated deviant, violent, aggressive behavior, but, obviously, ascertainment bias
  • Modern studies: delayed speech acquisition and other neurodevelopmental milestones, characterologic problems, psychiatric difficulties, average to below normal IQ; legal/medical now reject relationship between XYY and violent criminal behavior


  • X-linked disorder
  • Self-injurous behavior
  • Extrapyramidal involvement
  • Behavioral disturbances
  • Neuropsych presentation is variable



  • Rare group of genetic disorders which involve the destruction of CNS white mater (may also affect PNS)
  • Like MS, can also cause optic nerve, cerebellum, and spinal cord demyelination
  • Usually manifest as infants, but sometimes not until teens or young adults
  • Unremitting physical and mental deterioration


  • X-linked, recessive
  • Typically first produces neurologic symptoms and adrenal insufficiency in boys between 5 and 15 years
  • Occasionally develops in men aged 20-30 yrs, then associated by mania, gait impairment, and eventual dementia
  • “Lorenzo’s Oil” – reduces the accumulation of VLCFA’s, but DOES NOT alter the disease course
  • similarly, treatment by adrenal hormone replacement does not arrest the demyelination


  • Prenatal infections can lead to severe MR, convulsions, micro- or hydrocephalus
  • Maternal infections with psychological consequences: syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex, mumps, hepatitis, chicken pox (“STORCH”)


  • Low birth weight, meningoencephalitis, psychomotor and MR, cataracts/retinopathy, abnormalities of heart and major blood vessels


  • One of most common intrauterine infections
  • Enlargement of spleen and liver, intrauterine growth retardation, various congenital malformations, damage to visual and auditory systems, microcephaly, MR


  • Kernicterus, bilirubinemia (secondary to blood-type incompatibilities between mother and fetus), FAS


  • Protein-calorie malnutrition is a major problem worldwide
  • Protein/lipid deficiencies are developmental disorders with problems of myelination
  • Following two disorders are commonly combined rather than presenting separately


  • Protein deficient diet


  • Calorie deficient diet


  • Period around time of birth is time of greatest risk
  • Premature infant at particularly high risk because it is essentially unprepared for birth
  • May lead to MR, motor deficits, seizures, CP
  • Neurobehavioral sequelae vary depending on type of damage; in some cases, there is no sequelae


  • Perinatal mechanical damage can lead to intracranial hemorrhage and CNS tissue damage
  • Head injury from falls, MVA, abuse
  • >60% of all childhood cerebral neoplasms and >75% of all intracranial tumors are gliomas (i.e., glial cell tumors – e.g., astrocytoma, medulloblastoma, ependymoma)



  • First week of life
  • Most frequent neonatal neurological emergency
  • Usually result of serious perinatal conditions (e.g., anoxic episodes, hemorrhage)


  • Peak between 4-6 months
  • Characterized by spasms, severe MR, markedly abnormal EEG
  • Poor prognosis
  • Important to differentiate from reflux (as may look similar at first glance)


  • Typically occur 6 months-5 years
  • Little lasting effects with single seizure


  • Etiology may be trauma plus all pre-, peri-, and post-natal disorders (e.g., metabolic d/o, infection, anoxic episode)

Miscellaneous Info

  • Insulin-Dependent Diabetes – onset < 7years old and chronic course (>5 years) more likely to show reading and memory difficulties and slow response times
  • Brain dysfunction in children is associated with increased risk of psychiatric disorder, and vice versa; specifically, perinatal cerebral injuries constitute at least a weak risk factor for schizophrenia