286. In Hirschsprung’s disease, neural crest cells fail to migrate normally early in fetal development and produce potentially fatal complications within months of birth because of disturbed a. Intestinal motility b. Bladder control c. Swallowing d. Bile secretion e. Cardiac rhythms

286. The answer is a.( Victor, p 574.) Infants with this defect in develop-ment of the myenteric plexus are susceptible to intestinal obstruction and megacolon development. The affected infants are often misconstrued as merely colicky shortly after birth, but recurrent bouts of constipation, diar-rhea, and vomiting point to more serious disturbances of intestinal motil-ity. Intestinal obstruction is likely to become complete within the first year of life and may be fatal if not surgically corrected. The failure of migration of neural crest cells has been linked to a defect on chromosome 10

287. A newborn infant has a cystic swelling at the base of the spine that is covered with hyperpigmented skin and some coarse hair. Which of the fol- lowing is the most likely explanation? a. Mongolian spot b. Spina bifida occulta c. Nevus flammeus d. Meningocele e. Encephalocele

287. The answer is d. ( Victor, p 1062.) The Mongolian spot is a benign discoloration of the newborn’s skin at the base of the spine. It is usually oval, well circumscribed, flat, and slightly hyperpigmented or otherwise discolored. Spina bifida occulta is a defect in the superior elements of the spinal column that is unassociated with meningeal or spinal cord abnor- malities. It may be evidenced superficially by a dimple in the skin or a tuft of hair overlying the base of the spine. When there is evagination of the meninges (dura mater and pia arachnoid) about the cord or cauda equina through the defect in the spine, the condition is called a meningo- cele. Extrusion of meningeal and neural elements together is called a meningomyelocele. An encephalocele is a defect in the skull with extru- sion of brain. Nevus flammeus is a congenital, port-wine spot, usually developing on the face.

Items 288–289 At age 5, a child is noted to have the loss of ankle jerks. At age 10, limb ataxia develops, followed by a peripheral neuropathy. During adolescence, retinitis pigmentosa develops. Acanthocytosis is present. 289. In this disorder, chylomicrons, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) are largely absent in the serum as a con- sequence of a mutation in which gene? a. Microsomal triglyceride transfer protein (MTP) b. Huntingtin c. Amyloid precursor protein d. Dystrophin e. Transfer RNA (tRNA)

290. The answer is b. (Osborn, pp 815–816.) In the tomogram, the first cervical vertebra, or atlas, is incompletely formed. The most ventral ele- ments are apparent to the left of the left-pointing arrowhead, but the cor- tical bone of these elements is continuous with that of the skull. The elements of C1 that have formed have simply fused to the base of the skull. This assimilation of the atlas to the base of the skull is a congenital abnormality. It is often associated with a Chiari malformation of the hind- brain.

293. A 5-year-old boy has mental retardation, homonymous hemianopsia, and hemiparesis. He had infantile spasm and still has epilepsy. Head CT reveals calcifications in the cerebral cortex in a railroad track pattern. Which of the following does this child most likely have? a. Glioblastoma multiforme b. Oligodendroglioma c. Acoustic schwannoma d. Craniopharyngioma e. Sturge-Weber syndrome

293. The answer is e. (Greenberg, 2/e, p 601.) All of these disturbances will produce intracranial calcifications in some cases. The calcifications in Sturge-Weber syndrome follow the gyral pattern of the cerebral cortex and consequently produce the railroad track pattern that is evident on plain x-ray of the skull. Calcium is deposited in the brain of the patient with Sturge-Weber syndrome, presumably because the abnormal vessels overly- ing the brain allow calcium, as well as iron, across the defective blood- brain barrier. Craniopharyngioma and acoustic schwannoma produce calcifications, but these are obviously outside the cerebral cortex.

294. A 35-year-old woman has prenatal testing done. The testing reveals that her child will have phenylketonuria (PKU). With PKU, serum may exhibit dangerously high levels of a. Creatine phosphokinase (CPK) b. Nicotinamide c. Phenylketone d. Lactate dehydrogenase e. Phenylalanine

294. The answer is e.( Victor, pp 1008–1009.) Phenylketonuria is inher- ited as an autosomal recessive trait. It occurs in at least two forms. In one form, intolerance of phenylalanine is extreme, and dietary intake of that amino acid must be restricted from birth. Alternatively, some persons have hyperphenylalaninemia without PKU. This latter group does not suffer the CNS damage seen with in utero exposure to high phenylalanine levels. Such in utero exposure will occur if the mother is homozygous for PKU. If the mother is normal, infants with PKU are born with essentially normal nervous systems. Damage develops after birth in the susceptible group as serum phenylalanine levels rise.

295. A 4-year-old previously healthy girl develops an intermittent red, scaly rash over her face, neck, hands, and legs. This is followed by devel- opmental delay, emotional lability, and episodic cerebellar ataxia. She is diagnosed with Hartnup’s disease. Her condition may respond to large sup- plementary doses of a. Vitamin C b. Nicotinamide c. Thiamine d. Pyridoxine e. α tocopherol

295. The answer is b. ( Victor, pp 1009–1010.) With Hartnup’s disease there is intestinal malabsorption of tryptophan and other neutral amino acids. Tryptophan serves as a precursor for nicotinamide, but with more than 400 mg of nicotinamide daily, the tryptophan malabsorption becomes less problematic. Inheritance appears to be autosomal recessive. Affected children develop a scaly erythematous rash on the face similar to that seen with pellagra. The ataxia exhibited may be episodic.

296. Hepatosplenomegaly is most likely with a. Tay-Sachs disease b. Niemann-Pick disease c. Alpers’ disease d. Subacute necrotizing encephalopathy e. Wilson’s disease (hepatolenticular degeneration)

296. The answer is b. ( Victor, pp 997–998.) Niemann-Pick disease is inherited as an autosomal recessive trait. By 9 months of age, patients with the infantile form usually have prominent hepatosplenomegaly. A defi- ciency of sphingomyelinase in hepatocytes is diagnostic for the disease.

298. With agenesis of the corpus callosum, magnetic resonance imaging (MRI) will reveal a. Atrophy of the frontal lobes b. Abnormally shaped lateral and third ventricles c. Cerebellar aplasia d. Schizencephaly e. Encephaloclastic porencephaly

298. The answer is b.(Greenberg, 2/e, p 586–587.) On coronal sections of the brain, the lateral ventricles will have a typical batwing conformation if the patient has agenesis of the corpus callosum. The third ventricle may be dilated and may open onto the surface of the brain. Patients with this con- genital anomaly may be asymptomatic or may exhibit a variety of cognitive disorders. In Aicardi syndrome, agenesis of the corpus callosum is associ- ated with retardation, epilepsy, vertebral anomalies, and chorioretinitis.

Developmental and hereditary disorders Flashcards by dhira atman

In Hirschsprung’s disease, neural crest cells fail to migrate normally
early in fetal development and produce potentially fatal complications
within months of birth because of disturbed
a. Intestinal motility
b. Bladder control
c. Swallowing
d. Bile secretion
e. Cardiac rhythms

The answer is a.( Victor, p 574.) Infants with this defect in develop-ment of the myenteric plexus are susceptible to intestinal obstruction and
megacolon development. The affected infants are often misconstrued as
merely colicky shortly after birth, but recurrent bouts of constipation, diar-rhea, and vomiting point to more serious disturbances of intestinal motil-ity. Intestinal obstruction is likely to become complete within the first year
of life and may be fatal if not surgically corrected. The failure of migration
of neural crest cells has been linked to a defect on chromosome 10

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A newborn infant has a cystic swelling at the base of the spine that is
covered with hyperpigmented skin and some coarse hair. Which of the fol-
lowing is the most likely explanation?
a. Mongolian spot
b. Spina bifida occulta
c. Nevus flammeus
d. Meningocele
e. Encephalocele

The answer is d. ( Victor, p 1062.) The Mongolian spot is a benign
discoloration of the newborn’s skin at the base of the spine. It is usually
oval, well circumscribed, flat, and slightly hyperpigmented or otherwise
discolored. Spina bifida occulta is a defect in the superior elements of the
spinal column that is unassociated with meningeal or spinal cord abnor-
malities. It may be evidenced superficially by a dimple in the skin or a
tuft of hair overlying the base of the spine. When there is evagination of
the meninges (dura mater and pia arachnoid) about the cord or cauda
equina through the defect in the spine, the condition is called a meningo-
cele. Extrusion of meningeal and neural elements together is called a
meningomyelocele. An encephalocele is a defect in the skull with extru-
sion of brain. Nevus flammeus is a congenital, port-wine spot, usually developing on the face.

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At age 5, a child is noted to have the loss of ankle jerks. At age 10, limb
ataxia develops, followed by a peripheral neuropathy. During adolescence,
retinitis pigmentosa develops. Acanthocytosis is present.
288. These are all characteristic of which of the following?
a. Multiple sclerosis (MS)
b. Sickle cell disease
c. Abetalipoproteinemia
d. Progressive multifocal leukoencephalopathy (PML)
e. HIV subacute encephalomyelitis

The answer is a.( Rowland, pp 552–553.) This disorder appears to be
due to a mutation in the gene that encodes a subunit of the MTP, which
results in impaired VLDL formation and consequent decreased vitamin E
delivery to the peripheral and central nervous system. In addition to an
abnormal plasma lipid profile, patients have disturbed fat absorption. Pre-
sumably, it is the disturbed lipid that deforms the erythrocyte cell wall, but
erythrocyte production levels are relatively normal. Fat is increased in the
liver, and patients exhibit lactose intolerance. Central nervous system amy-
loid collections develop in Alzheimer’s disease.

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Items 288–289
At age 5, a child is noted to have the loss of ankle jerks. At age 10, limb
ataxia develops, followed by a peripheral neuropathy. During adolescence,
retinitis pigmentosa develops. Acanthocytosis is present.

In this disorder, chylomicrons, very-low-density lipoprotein (VLDL),
and low-density lipoprotein (LDL) are largely absent in the serum as a con-
sequence of a mutation in which gene?
a. Microsomal triglyceride transfer protein (MTP)
b. Huntingtin
c. Amyloid precursor protein
d. Dystrophin
e. Transfer RNA (tRNA)

The answer is b. (Osborn, pp 815–816.) In the tomogram, the first
cervical vertebra, or atlas, is incompletely formed. The most ventral ele-
ments are apparent to the left of the left-pointing arrowhead, but the cor-
tical bone of these elements is continuous with that of the skull. The
elements of C1 that have formed have simply fused to the base of the
skull. This assimilation of the atlas to the base of the skull is a congenital
abnormality. It is often associated with a Chiari malformation of the hind-
brain.

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In this tomogram of the base of the skull, the first cervical vertebra is
a. Unremarkable

b. Fused to the base of the skull
c. Completely absent
d. Displaced dorsally
e. Incorporated into the odontoid process (od)

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The second cervical vertebra extends above the level of the foramen
magnum and places the patient at high risk of having
a. A meningoencephalocele
b. A myelomeningocele
c. Syringobulbia
d. Syringomyelia
e. Brainstem compression

The answer is e. (Osborn, pp 815–816.) This abnormally situated
axis (C2) qualifies as basilar invagination of the skull. If the medulla oblon-
gata is situated at a normal level, it is at risk of compression, but posterior
fossa contents may be so caudally displaced that pontine structures are also at risk of compression. Hydrocephalus may develop with this degree of

basilar invagination by virtue of obstruction of the flow of CSF through the
foramen magnum. Syringomyelia or syringobulbia are occasionally associ-
ated with this anatomic variant, but they probably develop as a conse-
quence of cervical cord or brainstem damage.

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In view of the unusually wide separation (double-barbed arrow) of
caudal elements of the atlas from the odontoid process, one should suspect
a. Instability of the atlantoaxial joint
b. Hemorrhage into the atlantoaxial joint
c. Fusion of C2 to C3
d. Fracture of the odontoid process
e. Fracture of the C2 spinous process

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A 5-year-old boy has mental retardation, homonymous hemianopsia,
and hemiparesis. He had infantile spasm and still has epilepsy. Head CT
reveals calcifications in the cerebral cortex in a railroad track pattern.
Which of the following does this child most likely have?
a. Glioblastoma multiforme
b. Oligodendroglioma
c. Acoustic schwannoma
d. Craniopharyngioma
e. Sturge-Weber syndrome

The answer is e. (Greenberg, 2/e, p 601.) All of these disturbances
will produce intracranial calcifications in some cases. The calcifications in
Sturge-Weber syndrome follow the gyral pattern of the cerebral cortex and
consequently produce the railroad track pattern that is evident on plain
x-ray of the skull. Calcium is deposited in the brain of the patient with
Sturge-Weber syndrome, presumably because the abnormal vessels overly-
ing the brain allow calcium, as well as iron, across the defective blood-
brain barrier. Craniopharyngioma and acoustic schwannoma produce
calcifications, but these are obviously outside the cerebral cortex.

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A 35-year-old woman has prenatal testing done. The testing reveals
that her child will have phenylketonuria (PKU). With PKU, serum may
exhibit dangerously high levels of
a. Creatine phosphokinase (CPK)
b. Nicotinamide
c. Phenylketone
d. Lactate dehydrogenase
e. Phenylalanine

The answer is e.( Victor, pp 1008–1009.) Phenylketonuria is inher-
ited as an autosomal recessive trait. It occurs in at least two forms. In one
form, intolerance of phenylalanine is extreme, and dietary intake of that
amino acid must be restricted from birth. Alternatively, some persons have
hyperphenylalaninemia without PKU. This latter group does not suffer the
CNS damage seen with in utero exposure to high phenylalanine levels.
Such in utero exposure will occur if the mother is homozygous for PKU. If
the mother is normal, infants with PKU are born with essentially normal
nervous systems. Damage develops after birth in the susceptible group as
serum phenylalanine levels rise.

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A 4-year-old previously healthy girl develops an intermittent red,
scaly rash over her face, neck, hands, and legs. This is followed by devel-
opmental delay, emotional lability, and episodic cerebellar ataxia. She is
diagnosed with Hartnup’s disease. Her condition may respond to large sup-
plementary doses of
a. Vitamin C
b. Nicotinamide
c. Thiamine
d. Pyridoxine
e. α tocopherol

The answer is b. ( Victor, pp 1009–1010.) With Hartnup’s disease
there is intestinal malabsorption of tryptophan and other neutral amino
acids. Tryptophan serves as a precursor for nicotinamide, but with more
than 400 mg of nicotinamide daily, the tryptophan malabsorption becomes
less problematic. Inheritance appears to be autosomal recessive. Affected
children develop a scaly erythematous rash on the face similar to that seen
with pellagra. The ataxia exhibited may be episodic.

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Hepatosplenomegaly is most likely with
a. Tay-Sachs disease
b. Niemann-Pick disease
c. Alpers’ disease
d. Subacute necrotizing encephalopathy
e. Wilson’s disease (hepatolenticular degeneration)

The answer is b. ( Victor, pp 997–998.) Niemann-Pick disease is
inherited as an autosomal recessive trait. By 9 months of age, patients with
the infantile form usually have prominent hepatosplenomegaly. A defi-
ciency of sphingomyelinase in hepatocytes is diagnostic for the disease.

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A 25-year-old woman with epilepsy is taking divalproex sodium dur-
ing the first trimester of pregnancy. She is at slightly increased risk of hav-
ing children with which of the following?
a. Holoprosencephaly
b. Defects of neural tube closure
c. Medulloblastoma
d. Agenesis of the corpus callosum
e. Kallmann syndrome

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With agenesis of the corpus callosum, magnetic resonance imaging
(MRI) will reveal
a. Atrophy of the frontal lobes
b. Abnormally shaped lateral and third ventricles
c. Cerebellar aplasia
d. Schizencephaly
e. Encephaloclastic porencephaly

The answer is b.(Greenberg, 2/e, p 586–587.) On coronal sections of
the brain, the lateral ventricles will have a typical batwing conformation if
the patient has agenesis of the corpus callosum. The third ventricle may be
dilated and may open onto the surface of the brain. Patients with this con-
genital anomaly may be asymptomatic or may exhibit a variety of cognitive disorders. In Aicardi syndrome, agenesis of the corpus callosum is associ-

ated with retardation, epilepsy, vertebral anomalies, and chorioretinitis.

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A boy has the onset of difficulty walking at 16 months. Reflexes are
decreased. Over the course of several months, the patient becomes dysarthric
and mental functioning decreases. Testing reveals that the patient has a defi-
ciency of arylsulfatase A.
299. Which of the following does this patient most likely have?
a. Sandhoff’s disease
b. Tay-Sachs disease
c. Gaucher’s disease
d. Metachromatic leukodystrophy
e. McArdle’s disease

The answer is d.( Rowland, pp 521–523.) Hexosaminidase deficien-
cies produce Sandhoff’s and Tay-Sachs diseases. Glucocerebrosidase is defi-
cient in Gaucher’s disease. Phosphofructokinase deficiency is usually
symptomatic as a disturbance of skeletal muscle function. The enzymatic
defect in metachromatic leukodystrophy is transmitted in an autosomal
recessive fashion. The affected person usually has retardation, ataxia, spas-
ticity, and sensory disturbances, but individual elements of this disorder
may appear alone in less serious cases. The disease is usually symptomatic
during infancy.

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This diagnosis can usually be made on the basis of which of the fol-
lowing?
a. MRI
b. Nerve biopsy
c. Red blood cell (RBC) morphology
d. Cerebrospinal fluid (CSF) cell morphology
e. Electroencephalography (EEG)

The answer is b.( Rowland, pp 521–523.) Sulfatide granules may be
evident in nerve tissue, as well as in tissue outside the nervous system, in
persons with metachromatic leukodystrophy. The disease is usually fatal
within a few years of obvious symptoms. At autopsy, there may be evidence
of dysmyelination or demyelination in the CNS, as well as in the peripheral
nervous system.

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A 15-year-old boy has moderate mental retardation, attention deficit
disorder, a long face, enlarged ears, and macroorchidism. Development has
been steady but always at a delayed pace. The most likely cause for this
patient’s low intelligence is which of the following?
a. Turner syndrome
b. Klinefelter syndrome
c. Fragile X syndrome
d. Reye syndrome
e. Tuberous sclerosis

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Women carrying chromosomes for this disorder
a. Are invariably normal
b. Have mild retardation in about one-half of cases
c. Have high-arched palates and hypotelorism
d. Have hyperextensible joints
e. Have prominent thumbs

The answer is b.( Victor, p 1067.) Men with the fragile X syndrome
have hyperextensible joints and prominent thumbs, but carrier women
may appear quite normal. The abnormal chromosome may be detected in
fetal lymphocytes and fibroblasts, thereby allowing for prenatal screening.
Epilepsy develops in many affected persons, but the seizures are usually
easily controlled, unlike the case with other hereditary causes of epilepsy.

A 35-year-old man complains of stumbling and slurred speech. Hi
problem started several months ago and has progressed slowly but consis
tently. On neurologic examination, he is found to have scanning speech
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function i
normal.
303. The most appropriate initial investigation is
a. Lumbar puncture
b. Serum drug screen
c. Routine urinalysis
d. Posterior fossa myelogram
e. Precontrast CT scan

The answer is e. (Swaiman, pp 539–540.) This man has signs of
cerebellar dysfunction. That the deficit has been slowly progressive and is
not associated with cognitive dysfunction makes it especially likely that a
structural lesion in the posterior fossa is responsible for th e deficit. Because the lesion need not disturb the external shape of the cerebellum, a poste-

rior fossa myelogram will not necessarily yield an answer. The CT scan will
show if there is an intraparenchymal or extraparenchymal lesion. Drug
abuse is not likely to be a factor in this cerebellar syndrome, because all the
phenomena that are observed on examination are coordination problems
rather than combined cognitive and motor functions.

A 35-year-old man complains of stumbling and slurred speech. His
problem started several months ago and has progressed slowly but consis-
tently. On neurologic examination, he is found to have scanning speech,
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is
normal.
304. Admission studies include a hematocrit of 55% and a routine urinal-
ysis, which reveals excess protein and some RBCs in the urine. Urine cul-
ture is negative. The initial physical examination reveals an enlarged liver
and spleen. Additional physical findings will most likely include
a. A Kayser-Fleischer ring around the cornea
b. Hypopigmented (ash leaf) spots on the trunk
c. Telangiectasias in the fundi on retinal examination
d. Bilateral hearing loss
e. Generalized hyporeflexia

The answer is c.(Swaiman, pp 539–540.) The association of erythro-
cytosis with cerebellar signs, microscopic hematuria, and hepatospleno-
megaly suggests von Hippel-Lindau syndrome. This hereditary disorder is
characterized by polycystic liver disease, polycystic kidney disease, retinal
angiomas (telangiectasia), and cerebellar tumors. This is an autosomal dom-
inant inherited disorder with variable penetrance. Men are more commonly
affected than women. Although neoplastic cysts may develop in the cerebel-
lum in persons with von Hippel-Lindau syndrome, these usually do not
become sufficiently large to cause an obstructive hydrocephalus. Other
abnormalities that occur with this syndrome include adenomas in many
organs. Hemangiomas may be evident in the bones, adrenals, and ovaries.
Hemangioblastomas may develop in the spinal cord or brainstem, as well as
in the cerebellum. This syndrome is not associated with acoustic schwanno-
mas that could cause bilateral hearing loss, and it is not accompanied by
peripheral neuropathy, which could cause diffuse hyporeflexia.

A postcontrast computed tomography (CT) scan reveals a cyst and
two smaller masses in the left cerebellar hemisphere. Your recommenda-
tion is that the patient
a. Submit to surgical resection of the cerebellar lesions as soon as possible
b. Submit to radiation therapy of the cerebellar lesions immediately
c. Have follow-up MRI to look for involution of the lesions
d. Have a diagnostic lumbar puncture to look for evidence of parasitic infestation
of the brain
e. Have a needle biopsy of the cerebellum to establish the histology of the cystic
lesion

The answer is a.(Swaiman, pp 539–540.) The cystic lesion and the
other cerebellar lesions are most likely hemangioblastomas. These heman-
gioblastomas often bleed and produce potentially lethal intracranial
hematomas. Radiation therapy and needle biopsies would increase the risk
of bleeding. Rather than spontaneously involuting, these lesions generally
enlarge and become more unstable as time passes. Intracerebellar hemor-
rhage is increasingly likely as time passes.

Within 6 years of his initial visit, the patient returns with a patho-
logic fracture of his spine. Biopsy reveals metastatic cancer. The source of
the tumor is most likely the
a. Cerebral hemisphere
b. Cerebellar hemisphere
c. Liver
d. Kidney
e. Spleen

The answer is d. (Swaiman, pp 539–540.) Von Hippel-Lindau syn-
drome is associated with a high incidence of renal carcinomas. These
malignant renal tumors usually develop years after the cerebellar heman-
gioblastomas, liver disease, or polycystic renal disease becomes sympto-
matic. People surviving intracranial hemorrhages caused by the
intracerebellar hemangioblastomas often succumb to metastatic renal carcinoma. Treating the intracranial lesions does nothing to reduce the risk of

metastatic renal cancer.

An infant has a head CT performed because of a large head and failure
to thrive. The diagnosis of hydrocephalus is made.
307. Congenital hydrocephalus may develop as a consequence of which
first-trimester maternal disorder?
a. Complicated migraine
b. Viral infection
c. Pseudotumor cerebri
d. Chorea gravidarum
e. Intervertebral disk herniation

The answer is b.(Greenberg, 2/e, p 597. Rowland, pp 5142–5143.) A
maternal infection with mumps or rubella virus may produce aqueductal
stenosis and, as a consequence, hydrocephalus. The aqueduct of Sylvius
connects the third ventricle to the fourth ventricle. The lateral and third
ventricles enlarge as the choroid plexus produces fluid that cannot migrate
to the subarachnoid space to be reabsorbed.

An infant has a head CT performed because of a large head and failure
to thrive. The diagnosis of hydrocephalus is made.

Uncorrected congenital hydrocephalus will usually produce which
of the following?
a. Dolichocephaly
b. Brachycephaly
c. Holoprosencephaly
d. Macrocephaly
e. Microcephaly

The answer is d. ( Victor, pp 661–662.) Congenital hydrocephalus
usually requires shunting to avoid progressive enlargement of the head and
thinning of the brain mantle. Dolichocephaly and brachycephaly refer to
head shapes, the former being a long, narrow head and the latter a broad
head. Neither of these is necessarily associated with any abnormality. Holo-
prosencephaly is a failure in development of the midline division of the
brain, which may give rise to a stillborn cyclops. A variety of conditions
will produce congenital hydrocephalus, and any condition that produces
apparent hydrocephalus at birth may produce mental retardation. Correc-
tion of the hydrocephalus at or soon after birth reduces the probability of
retardation as a direct effect of the hydrocephalus, but conditions that
cause damage to the brain as well as obstruct the flow of CSF may leave the
patient retarded. An uncorrected hydrocephalus may not be lethal for
many years.

A 6-month-old child is noted to have head lag, tongue fasciculations,
and bilateral abducens palsies. MRI scan reveals a type 2 Chiari malforma-
tion. Which of the following defects would this child be likely to have?
a. A renal cyst
b. Pulmonary atelectasis
c. Spina bifida
d. Holoprosencephaly
e. A hepatic cyst

A 7-year-old boy is taken by his parents to see a dermatologist. They have noticed nodules on his face and are concerned. The dermatologist tells them that their child has adenoma sebaceum. 310. Adenoma sebaceum of the face is especially common with which of the following diseases? a. Neurofibromatosis b. Sturge-Weber syndrome c. Tuberous sclerosis d. Ataxia telangiectasia e. Fragile X syndrome

310. The answer is c.( Victor, pp 1069–1073.) Adenoma sebaceum occurs in about 90% of patients with tuberous sclerosis. A depigmented lesion, called a shagreen patch, occurs in only about 20% of these patients. Ade- noma sebaceum usually becomes apparent over the malar eminences of the face between 2 and 5 years of age and may evolve into difficult-to-treat angiofibromas of the skin. In ataxia telangiectasia, facial telangiectasias may develop. Sturge-Weber syndrome is characteristically associated with a port- wine spot over part of the face. Patients with neurofibromatosis often have café au lait spots, but these do not usually occur on the face.

A 7-year-old boy is taken by his parents to see a dermatologist. They have noticed nodules on his face and are concerned. The dermatologist tells them that their child has adenoma sebaceum. 311. This disease is inherited in a. A sex-linked recessive pattern b. An autosomal dominant pattern c. An autosomal recessive pattern d. A pattern most consistent with newly arising mutations e. A pattern suggesting a mitochondrial gene defect

311. The answer is b. ( Victor, pp 1069–1073.) Although the inheritance pattern of tuberous sclerosis is autosomal dominant, the penetrance is vari- able. A severely impaired child may be born to a negligibly affected parent. Despite the consensus that inheritance is autosomal dominant, estimates of spontaneous mutations in affected persons are as high as 70%.

A 7-year-old boy is taken by his parents to see a dermatologist. They have noticed nodules on his face and are concerned. The dermatologist tells them that their child has adenoma sebaceum. 312. Retinal problems with this disease a. Include retinal phakomas b. Include retinitis pigmentosa c. Include retinal telangiectasias d. Include retinoblastomas e. Are generally not part of the disease

312. The answer is a.( Victor, p 1071.) Retinal phakomas, which require no treatment, are a principal criterion for making the diagnosis of tuberous sclerosis. Along with adenoma sebaceum and periventricular tubers, they are virtually pathognomonic. Other findings that are typical of tuberous sclerosis include ash leaf spots, shagreen patches, CNS calcifications, renal tumors, cardiac rhabdomyomas, and seizure disorders.

A 7-year-old boy is taken by his parents to see a dermatologist. They have noticed nodules on his face and are concerned. The dermatologist tells them that their child has adenoma sebaceum. 313. Calcifications evident on the skull x-ray or CT scan of a patient with this disease usually represent a. Calcified subependymal glial nodules b. Calcified meningeal adhesions c. Meningeal psammoma bodies d. Calcified astrocytomas e. Calcified granulomas

314. A 50-year-old man complaining of dizziness is found to have a cyst occupying 50% of his posterior fossa and incomplete fusion of the cerebel- lar elements inferiorly. There is no evidence of an obstructive hydro- cephalus. His longevity can be estimated to be a. Less than 3 months b. Less than 1 year c. Less than 5 years d. Less than 10 years e. Unaffected by this finding

315. The treatment of choice for children with infantile spasms is a. Carbamazepine (Tegretol) b. Phenobarbital c. Phenytoin (Dilantin) d. Divalproex sodium (Depakote) e. Adrenocorticotropic hormone (ACTH)

316. A 9-year-old boy has been generally healthy. However, his parents are concerned that his many areas of hyperpigmented skin may have some sig- nificance. They have been told that these are café au lait spots. Café au lait spots are commonly found on patients with a. Tuberous sclerosis b. Neurofibromatosis c. MS d. Sturge-Weber syndrome e. Ataxia telangiectasia

316. The answer is b. ( Victor, pp 1073–1077.) Café au lait spots in patients with neurofibromatosis are usually larger than a few centimeters and occur in several locations in individual patients. Some have ragged edges and are called coast of Maine spots. They occur with both type 1 and type 2 neurofibromatosis, but are much more common with type 1.

317. The newborn infant with motor neuron disease is likely to exhibit a. Seizures b. Hypotonia c. Hypsarrhythmia d. Moro reflexes e. Spina bifida

317. The answer is b.(Swaiman, pp 1164–1169.) The child with congen- ital weakness, hypotonia, and muscle atrophy may have Werdnig- Hoffmann disease, a congenital motor neuron disease. This is an especially lethal form of motor neuron disease and may limit the child’s life expectancy to weeks or months. A similar pattern of disease that appears in older children is less lethal and is called Kugelberg-Welander disease. These types of motor neuron diseases are also known as spinal muscular atrophies (SMAs). Anterior horn cell disease is presumed to be a pivotal feature of diseases in this category.

318. Many children with Tay-Sachs disease develop blindness before they die, with retinal accumulation of gangliosides that produces a. Optic neuritis b. Cherry red spots c. Chorioretinitis d. Retinal detachments e. Waxy exudates

318. The answer is b.( Victor, pp 996–997.) More than 90% of children with Tay-Sachs disease develop cherry red spots on the retina. The red spot at the fovea develops as retinal ganglion cells become distended with glycolipid. There are no ganglion cell bodies overlying the fovea, and so the red color of the vascular choroid is apparent in this region but obscured by more opaque glycolipid-engorged cells over the remainder of the retina.

319. The parents of a 10-year-old boy bring their child in to see you. The child has been diagnosed with cerebral palsy, and the parents do not really understand what this means. As part of your explanation, you tell them that cerebral palsy is a static encephalopathy because a. Deficits do not appear after birth b. The injury to the brain does not progress c. Affected persons fail to reach any developmental milestones on time d. Affected persons have resting tremors e. The EEG exhibits a disorganized background rhythm

319. The answer is b.( Rowland, p 476.) A static encephalopathy is one in which brain damage has been arrested but neurologic problems persist. Establishing that the brain lesion is not progressive may require extensive testing. A young child with a static motor disorder is said to have CP. Neu- rodegenerative diseases with slow or stepwise progressions may appear to be static encephalopathies over the course of months, but prove to be pro- gressive encephalopathies over the course of years. The brain lesion with CP is static, but the deficits associated with CP may evolve as the child matures.

320. A 6-year-old child is brought to the neurologist because of develop- mental delay. Her morphological features are typical and chromosome analysis confirms a diagnosis of Down syndrome (trisomy 21). The brain of this patient is expected to be a. Smaller than normal for age and body size b. Larger than normal for age and body size c. Abnormally long in anteroposterior measurements d. Hydrocephalic e. Excessively convoluted

321. Porencephaly usually develops as a consequence of a. Fetal alcohol syndrome b. Vascular or other destructive injuries to the fetal brain c. Trisomy 13 d. Trisomy 21 e. Dandy-Walker syndrome

321. The answer is b. (Osborn, pp 52–56.) In utero damage to the fetal brain may be evident at birth as large cysts in the brain. The presence of one or more of these intracerebral cysts is called porencephaly. Some pathologists believe that schizencephaly, a related abnormality in which brain segmentation is abnormal, is caused by similar phenomena, which include incidents such as strokes and viral encephalitides in the fetal brain.

322. What percentage of patients with tuberous sclerosis have mental retardation? a. 1 b. 10 c. 25 d. 65 e. 99

322. The answer is d. (Swaiman, p 534.) Of the 65% of patients with tuberous sclerosis who are retarded, half are severely retarded. Seizures are invariably associated with retardation. About 20% of patients with tuber- ous sclerosis develop the Lennox-Gastaut syndrome with persistent seizures and significant mental retardation. These children usually have a mixed seizure disorder, whereas those without Lennox-Gastaut syndrome most often have complex partial seizures.

323. A child is born to a 19-year-old woman who has had two to eight drinks per day throughout her pregnancy. What is the major pathologic effect of alcohol on the central nervous system of the developing fetus? a. Cerebral ischemia b. Periventricular hemorrhage c. Macrocephaly d. Impaired neuronal migration e. Holoprosencephaly

324. A 37-year-old man has an MRI performed by his primary care doctor because of a long history of headaches. It is notable only for the finding of a type 1 Chiari malformation. He is sent to a neurologist for further eval- uation. A type 1 Chiari malformation usually becomes symptomatic as which of the following in adults? a. Epilepsy b. Hydrocephalus c. Ataxia d. Dementia e. Psychosis

324. The answer is c.(Osborn, pp 15–18.) Both type 1 and type 2 Chiari malformations are primarily abnormalities of hindbrain development. With the type 1, or adult, abnormality, the cerebellar tonsils extend below the foramen magnum. Affected persons do not usually become symptomatic until they are adults, and then the symptoms are largely referable to the cerebellum. With the type 2 malformation, cerebellar anatomy is usually much more deranged, and the cerebellar vermis lies well below the foramen magnum. Type 2 malformations most often become symptomatic at birth or during infancy and may produce hydrocephalus with retardation.

325. A 25-year-old mother develops an illness during pregnancy. A diag- nosis of cytomegalovirus (CMV) infection is made by serology. Prenatal CMV infections may produce which retinal disturbance? a. Chorioretinitis b. Cherry red spot c. Microaneurysms d. Hypervascularity e. Hemorrhage

325. The answer is a.( Victor, p 1071.) Microaneurysms and hypervascu- larity are typically seen with diabetic retinopathy rather than developmen- tal disease. Hemorrhages in the retina would be more typical of hypertensive encephalopathy or a coagulopathy. Neurologic problems that develop in the infant with a prenatal CMV infection include retardation, microcephaly, seizures, and hearing deficits. The virus often causes cho- rioretinitis, optic atrophy, and architectural changes throughout the brain.