Pediatric Examination and Board Review (226 page)

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait with variable penetrance

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) relatively little is known about the mode of transmission of this disorder

6.
Which of the following seizure types is
not
more common in TSC?

(A) infantile spasms

(B) complex partial seizures

(C) absence seizures

(D) simple partial seizures

(E) atonic seizures

7.
When would you most likely expect adenoma sebaceum (facial angiofibromas) to present in this child?

(A) shortly after birth

(B) between 1 and 4 years

(C) between 6 and 9 years

(D) during puberty

(E) adulthood

8.
An 18-month-old girl presents to your clinic for continued pediatric care. Her family recently moved to your area and you haven’t yet received her medical records. On physical examination, she has a nevus flammeus (port wine stain) over the left side of her face and a contralateral hemiparesis. This patient is most likely to have which of the following?

(A) ipsilateral leptomeningeal angioma

(B) intracranial calcifications on head CT

(C) glaucoma

(D) A and B

(E) all of the above

9.
Which of the following statements is true regarding the genetics of Sturge-Weber syndrome?

(A) it is transmitted as an autosomal recessive trait

(B) it is transmitted as an autosomal dominant trait

(C) the disorder demonstrates an X-linked mode of inheritance

(D) the disorder is the result of triplet repeat expansion

(E) relatively little is known about the mode of transmission of this disorder

10.
Each of the following neurocutaneous disorders is transmitted as an autosomal dominant trait except for

(A) NF 1

(B) Von Hippel-Lindau disease

(C) TSC

(D) ataxia-telangiectasia

(E) NF 2

11.
A 26-month-old boy presents to your clinic for an evaluation of multiple café au lait spots. On close inspection, you determine that he has 6 spots larger than 0.8 cm over the trunk. On funduscopic examination, you notice optic disc pallor in the left eye. The most likely cause of the optic disc pallor and atrophy is which of the following?

(A) optic neuritis

(B) papilledema

(C) optic nerve glioma

(D) meningioma

(E) retinal artery infarction

12.
The father of the patient in question 11 offers that he has similar birthmarks to that of his son. The most likely diagnosis is which of the following?

(A) NF 2

(B) NF 1

(C) ataxia-telangiectasia

(D) neurocutaneous melanosis

(E) linear sebaceous nevus

13.
Which of the following is the most common CNS tumor observed in NF 1?

(A) low-grade astrocytoma

(B) meningioma

(C) medulloblastoma

(D) ependymoma

(E) primitive neuroectodermal tumors

14.
Which of the following is not a diagnostic criterion of NF1?

(A) two or more Lisch nodules

(B) optic nerve glioma

(C) five or more café au lait spots 1.5 cm or larger in postpubertal individuals

(D) a first-degree relative with NF1

(E) two or more neurofibromas or one or more plexiform neurofibroma

MATCH EACH OF THE FOLLOWING DIAGNOSTIC FEATURES WITH ITS NEUROCUTANEOUS DISORDER

15.
Bilateral acoustic neuromas        (A) neurofibromatosis 1

16.
Periungual fibroma                     (B) Von Hippel-Lindau disease

17.
Retinal hemangioblastoma          (C) NF 2
                                                 (D) ataxia-telangiectasia

18.
Decreased
immunoglobulin A
and E levels                               (E) TSC

19.
Café au lait spots

ANSWERS

1.
(A)
This patient most likely has infantile spasms given the clinical history and observations. Infantile spasms typically occur between 3 and 8 months of age. Although there are many causes of infantile spasms, such as intrauterine infections and perinatal asphyxia, it is the most common seizure type seen in tuberous sclerosis complex (TSC). Patients typically have myoclonic jerks in clusters that usually occur on awakening. The seizures can consist of head and body flexion or extension. The movements observed in this child are the more common presentation. As seen in this child, the loss of milestones and developmental arrest are not uncommon at the onset of infantile spasms. The presence of hypopigmented spots supports the diagnosis of TSC and, to some extent, infantile spasms. Approximately half the patients with TSC can have cardiac rhabdomyomas. The cardiac rhabdomyomas affect the myocardium and can be solitary, multiple, or infiltrative. Cardiac rhabdomyomas can cause arrhythmias, congestive heart failure, obstruction to blood flow, or even sudden death. The arrhythmias include ventricular tachycardia, supraventricular tachycardia (SVT), and Wolff-Parkinson-White syndrome. It is important to clarify the arrhythmia and begin the necessary treatment. An echocardiogram will probably reveal a cardiac rhabdomyoma.

2.
(C)
To make a definite diagnosis of TSC, 2 of 11 major features or 1 major feature plus 2 of 9 minor features must be present. The features are listed here (slightly modified from Kandt, 2002):

Major diagnostic features:

Cardiac rhabdomyoma

Renal angiomyolipoma

Lymphangiomyomatosis

Facial angiofibromas

Ungual fibroma

Shagreen patch

Cortical tuber

Three or more hypomelanotic macules

Multiple retinal nodular hamartomas

Subependymal giant cell astrocytoma

Subependymal nodule

Minor diagnostic features:

Multiple renal cysts

Retinal achromic patch

Multiple dental pits

Bone cysts

Nonrenal hamartoma

Gingival fibromas

“Confetti” skin lesions

Cerebral white matter radial migration lines

Hamartomatous rectal polyps

Patients who have the hypomelanosis of Ito have hypopigmented skin lesions, which vary from linear streaks following a dermatomic distribution to whorls with irregular margins. Females are more frequently affected than males. Periventricular calcifications, tubers, and subependymal nodules are not observed. Fahr disease (familial basal ganglia calcification) is a hereditary condition in which calcification is particularly observed in the dentate and lenticular nuclei. The disease is not associated with hypopigmented skin lesions. Toxoplasmosis is caused by the protozoan
Toxoplasma gondii
. The major reservoir for this organism in the United States is the cat, which excretes oocysts in the feces. The disease is associated with cerebral calcification in approximately 60% of affected individuals. Although seizures, hydrocephalus, microcephaly, chorioretinitis, and psychomotor retardation are seen in toxoplasmosis, skin lesions are not described.

3.
(E)
Patients with TSC are at risk for developing all of the complications described. Most renal tumors are renal cysts or renal angiomyolipomas. However, a small percentage of patients (<2%) develop renal carcinoma. For reasons that are unclear, female patients are at risk to develop pulmonary complications. Tubers can obstruct normal cerebrospinal fluid (CSF) flow if located near the foramen of Monro or the Sylvian aqueduct.

4.
(D)
The American Academy of Neurology recently published a practice parameter reviewing the medical treatment of infantile spasms. The recommendation is that ACTH is probably effective in the short-term treatment of infantile spasms. Vigabatrin may be useful in the treatment of infantile spasms, particularly caused by TSC. However, this medication is not Food and Drug Administration approved because it causes retinal toxicity.

5.
(B)
TSC is transmitted as an autosomal dominant trait with variable penetrance. However, spontaneous mutation rates may be observed in more than 50% of patients.

6.
(C)
Absence seizures cause a primary generalized seizure disorder and are not seen more frequently in TSC.

7.
(B)
Some lesions seen in TSC occur at various developmental stages. Adenoma sebaceum typically develops at 1-4 years. It rarely is seen at birth.

8.
(E)
This patient probably has Sturge-Weber syndrome, which is characterized by a facial angioma (nevus flammeus, or port wine stain) and ipsilateral leptomeningeal angioma. The facial angioma typically involves the upper face and occasionally the nasopharynx, mucous membranes, and/or ocular choroidal membrane (see
Figure 132-1
). Choroidal membrane involvement can lead to glaucoma in approximately 25% of patients. Neuroimaging studies demonstrate calcium deposits in the walls of some small cerebral vessels and outer cortical layers. This is best observed on head CT. In one study, seizures occurred in three-quarters of the cases. Patients can have a contralateral hemiparesis with hemiatrophy. Hemianopsia is also observed.

FIGURE 132-1.
Extensive right facial capillary malformation (
A
) involving the ophthalmic and maxillary branches of the trigeminal nerve in a 6-month-old girl affected with Sturge-Weber syndrome. Choroid capillary-venous malformation (
B
) causing vision loss in a 50-year-old man with Sturge-Weber syndrome. (Reproduced, with permission, from Wolff K, Goldsmith LA, Katz SI, et al. Fitzpatrick’s Dermatology in General Medicine, 7th ed. New York: McGraw-Hill; 2008: Fig. 173-4A,B.)

9.
(E)
No clear evidence of heredity has been discovered for this disorder.

10.
(D)
Ataxia-telangiectasia is a neurocutaneous disorder characterized by progressive cerebellar ataxia, immune defects, oculocutaneous telangiectasis, and a predisposition to malignancy (see
Figure 132-2
). Patients have a tendency to develop sinopulmonary infections and skin infections. Cellular and humoral immunity can be impaired. The disease is transmitted in a sporadic or autosomal recessive manner.