Developmental and Hereditary Disorders Flashcards
Developmental and Hereditary Disorders
1
Q
- 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
A
- The answer is a. (Victor, p 574.) Infants with this defect in development
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, diarrhea,
and vomiting point to more serious disturbances of intestinal motility.
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.
2
Q
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 following is the most likely explanation? a. Mongolian spot b. Spina bifida occulta c. Nevus flammeus d. Meningocele e. Encephalocele
A
- 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 abnormalities.
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 meningocele.
Extrusion of meningeal and neural elements together is called a
meningomyelocele. An encephalocele is a defect in the skull with extrusion
of brain. Nevus flammeus is a congenital, port-wine spot, usually
developing on the face.
3
Q
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.
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
A
- The answer is c. ( Rowland, pp 552–553.) Abetalipoproteinemia
(Bassen-Kornzweig syndrome) usually becomes symptomatic during
early childhood. The peripheral blood smear will exhibit abnormally
shaped erythrocytes (acanthocytes), and the plasma lipid profile will
reveal a very low cholesterol and triglyceride content. Acanthocytes are
spiked or crenated RBCs. These are an unusual hematologic finding in
patients with ataxia and are often diagnostic of abetalipoproteinemia.
Autopsy examination of the CNS in patients with abetalipoproteinemia reveals posterior column and spinocerebellar tract degeneration. The initial
complaints are similar to the spinocerebellar signs of Friedreich’s disease.
Position sense is lost and extensor plantar responses develop as the
disease progresses. As is true for Friedreich’s disease, dementia is not an
obvious part of the syndrome. Deficits accumulate over the course of
years. Vitamin E supplementation may retard the disease’s progression.
The differential diagnosis of retinitis pigmentosa is broad, and includes
many other conditions besides abetalipoproteinemia: mitochondrial diseases,
Bardet-Biedl syndrome, Laurence-Moon syndrome, Friedreich’s
ataxia, and Refsum’s disease. It may also occur alone as a hereditary disorder
linked to chromosome 3. It is characterized by a degeneration of all
layers of the retina. Because it is a noninflammatory condition, retinitis is
actually something of a misnomer.
4
Q
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 consequence
of a mutation in which gene?
a. Microsomal triglyceride transfer protein (MTP)
b. Huntingtin
c. Amyloid precursor protein
d. Dystrophin
e. Transfer RNA (tRNA)
A
- 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. Presumably,
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 amyloid
collections develop in Alzheimer’s disease.
5
Q
- 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
A
- 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 overlying
the brain allow calcium, as well as iron, across the defective bloodbrain
barrier. Craniopharyngioma and acoustic schwannoma produce
calcifications, but these are obviously outside the cerebral cortex.
6
Q
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
A
- The answer is e. (Victor, pp 1008–1009.) Phenylketonuria is inherited
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.
7
Q
- A 4-year-old previously healthy girl develops an intermittent red,
scaly rash over her face, neck, hands, and legs. This is followed by developmental
delay, emotional lability, and episodic cerebellar ataxia. She is
diagnosed with Hartnup’s disease. Her condition may respond to large supplementary
doses of
a. Vitamin C
b. Nicotinamide
c. Thiamine
d. Pyridoxine
e. α tocopherol
A
- 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.
8
Q
- 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)
A
- 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 deficiency
of sphingomyelinase in hepatocytes is diagnostic for the disease.
9
Q
297. A 25-year-old woman with epilepsy is taking divalproex sodium during the first trimester of pregnancy. She is at slightly increased risk of having 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
A
- The answer is b. (Greenberg, 5/e, p 274.) To what extent the
antiepileptic divalproex sodium increases the risk of defects of neural tube
closure, such as meningomyelocele, is debatable, but there is at least a
slight increase in the risk. Many agents have been linked to problems with
neural tube formation or closure, but none causes problems in a large segment
of the population. Colchicine, papaverine, and caffeine, as well as
irradiation, hyperthermia, antimetabolites, and salicylates, may increase
the risk of neural tube malformations. The vitamin most clearly implicated
in cases involving hypervitaminosis is vitamin A. Congenital malformations
as a group are slightly increased in the offspring of women with
epilepsy even if they are not taking antiepileptic drugs before or during
pregnancy. The importance of folate supplementation in women with a
prior history of neural tube defect has been shown in several studies and is
the basis of the recommendation for the use of folate supplementation during
the first trimester of pregnancy. Agenesis of the corpus callosum is a
component of several developmental disorders of the CNS, including
Chiari syndromes. Kallmann syndrome is a congenital disturbance of the
hypothalamus that results in anosmia, hypogonadism, and other maturational
problems that become more evident when puberty fails to occur.
10
Q
- 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
A
- 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 congenital
anomaly may be asymptomatic or may exhibit a variety of cognitive
212 Neurology
disorders. In Aicardi syndrome, agenesis of the corpus callosum is associated
with retardation, epilepsy, vertebral anomalies, and chorioretinitis.
11
Q
Items 299–300
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 deficiency
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
A
- The answer is d. (Rowland, pp 521–523.) Hexosaminidase deficiencies
produce Sandhoff’s and Tay-Sachs diseases. Glucocerebrosidase is deficient
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, spasticity,
and sensory disturbances, but individual elements of this disorder
may appear alone in less serious cases. The disease is usually symptomatic
during infancy.
12
Q
Items 299–300
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 deficiency
of arylsulfatase A.
- This diagnosis can usually be made on the basis of which of the following?
a. MRI
b. Nerve biopsy
c. Red blood cell (RBC) morphology
d. Cerebrospinal fluid (CSF) cell morphology
e. Electroencephalography (EEG)
A
- 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.
13
Q
Items 301–302
301. 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
A
- The answer is c. (Bradley, p 83.) With the fragile X syndrome, the
terminal elements of the long arm of the abnormal X chromosome appear
stretched or broken away from the rest of the chromosome. Retardation
usually becomes evident during childhood. Affected men have large ears, a
high-arched palate, hypotelorism, and large testes. Autism also occurs
among affected men.
14
Q
Items 301–302
301. 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?
302. 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
A
- 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.
15
Q
Items 303–306
A 35-year-old man complains of stumbling and slurred speech. His
problem started several months ago and has progressed slowly but consistently.
On neurologic examination, he is found to have scanning speech,
nystagmus, limb dysmetria, and kinetic tremor. His intellectual function is
normal.
- The most appropriate initial investigation is
a. Lumbar puncture
b. Serum drug screen
c. Routine urinalysis
d. Posterior fossa myelogram
e. Precontrast CT scan
A
- 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 the deficit. Because
Developmental and Hereditary Disorders
the lesion need not disturb the external shape of the cerebellum, a posterior
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.
