Developmental and Hereditary Disorders Flashcards
- 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
(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, 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.
- 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
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.
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.
- 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
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.
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
(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.
- 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)
B
(Osborn, pp 815–816.) In the tomogram, the first cervical vertebra, or atlas, is incompletely formed. The most ventral elements are apparent to the left of the left-pointing arrowhead, but the cortical 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 hindbrain.
- 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
E
(Osborn, pp 815–816.) This abnormally situated axis (C2) qualifies as basilar invagination of the skull. If the medulla oblongata 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 associated with this anatomic variant, but they probably develop as a consequence of cervical cord or brainstem damage.
- 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
A
(Victor, p 1327.) The separation between the atlas and the odontoid process of the axis may change by several millimeters with flexion and extension of the neck. Extremes of position may actually be dangerous because of compression of the brainstem or of major arteries coursing through the foramen magnum. Instability of the joint may develop with fracture of the odontoid process, but in that situation the body of C2, rather than the odontoid process, will exhibit excessive slip in relation to C1 when the neck is flexed or extended. Fusion of other cervical vertebrae is not unusual in patients exhibiting anomalies at the base of the skull.
- 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
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 blood-brain barrier. Craniopharyngioma and acoustic schwannoma produce calcifications, but these are obviously outside the cerebral cortex.
- 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
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.
- 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
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.
- 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)
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.
- 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
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.
- 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
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 disorders. In Aicardi syndrome, agenesis of the corpus callosum is associated with retardation, epilepsy, vertebral anomalies, and chorioretinitis.
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.
- 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
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.
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)
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.
- 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
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.
