Developmental Diseases of the NS

Question 1

Marked enlargement of one cerebral hemisphere as a result of a developmental abnormality. Usu. Cognitively delayed. Some have epilepsy.

Answer 1

Hemimegalencephaly

Question 2

There are individuals whose heads and brains are enlarged but who are normal in all other respects. This has been shown to be inherited in what pattern?

Answer 2

Autosomal dominant

Question 3

Common congenital defect associated with macrocephaly, varying degrees of mental impairment, optic defects and seizures and on CT is revealed as a “bat-wing” deformity of the ventricles.

Answer 3

Agenesis of the corpus callosum.

Question 4

Most severe and lethal of the craniostenoses.

Answer 4

Clover-shaped skull

Question 5

Two genetic variations of Down Syndrome

Answer 5

1. Triplication of Chromosome 21

2. Translocation therefore duplication of distal portion of long arm of chromosome 21

Question 6

H3O mnemonic for Prader-Willi Syndrome and associated genetic defect

Answer 6

Hypotonia
Hypomentia
Hypogonadism
Obesity (from hyperphagia)

Microdeletion 15q11-q13
70% noninherited deletion from paternl X chromosome

Question 7

Syndrome that is associated with an identical chromosomal abnormality to that of Prader-Willi syndrome but maternally inherited, presenting with developmental delay, microcephaly, refractory seizures inappropriate laughter, absence of speech ataxia, prominent jaw, thin upper lip

Answer 7

Angelman syndrome

Question 8

Most common anomaly attributable to anticonvulsant drugs

Answer 8

Cleft lip and palate

Others reported:
Craniofacial defects
Spina bifida
Minor cardiac defects
Dysraphisms

Question 9

Features the phakomatoses have in common

Answer 9

1. Hereditary transmission
2. Involves organs of ectodermal origin
3. Slow evolution of lesions in childhood and adolescence
4. Tendency to form hamartomas
5. Disposition to fatal malignant transformation

Question 10

Characteristic triad of Tuberous Sclerosis?

Two diagnostic dermal features of the disease?

Answer 10

Adenoma sebaceum, Epilepsy & developmental delay

“Ash-leaf” lesions - hypomelanotic skin macules
Subepidermal fibrotic Shagreen patch

Question 11

Genetic abnormality in Tuberous Sclerosis?

Answer 11

In one of the ff:

TSC1 (hamartin) on long arm of chromosome 9
TSC2 (tuberin) on short arm of chromosome 16

Question 12

Lesion pathognomonic of Tuberous Sclerosis

Answer 12

Adenomas of Pringle - well-developed facial lesions angiofibromas, red to pink nodules with smooth glistening surface limited to nasolabial folds, cheeks, chin (occ forehead and scalp)

Question 13

Radiologic surveillance to detect enlargement of subependymal tumors in Tuberous Sclerosis

Answer 13

Annually for <21y

Then every 2-3yrs after

Question 14

Symptom common in adults with NF1 often related to a malignant peripheral nerve sheath tumor

Answer 14

Pain

Question 15

This distinguishes molluscum fibrosum of NF1 from other skin tumors such as multiple lipoma

Answer 15

“buttonholing” - when pressed, these soft tumors tend to invaginate through a small opening in the skin

Question 16

Defective protein in Ataxia-Telangiectasia. Absent in 90% of those with the disease

Answer 16

ATM protein - a kinase that’s a transducer in the pathway for DNA repair that halts the cell cycle after DNA damage

Question 17

Ataxia-Telangiectasia or Louis-Bar syndrome

Answer 17

Autosomal recessive

Progressive ataxia with humoral immune deficiency and telangiectasia

Question 18

Two mutant genes identified as causes of the Osler-Rendu-Weber Disease

Answer 18

endoglin

novel kinase

Question 19

Causative mutation and pattern of inheritance of von Hippel-Lindau disease

Answer 19

Mutation in the VHL gene on chromosome 3

Autosomal dominant with variable but high penetrance by older age

Question 20

Characteristic finding of Sturge Weber Syndrome on Skull films taken after the 2nd year

Answer 20

“tramline” calcification which outlines the involved convolutions of the parietooccipital cortex

Question 21

Hutchinson triad

Answer 21

Dental deformities
Interstitial keratitis
Bilateral deafness

Seen albeit infrequently in its complete form in congenital syphilis

Question 22

An acoustic neuroma developing before this age should be suspected to be caused by NF2

Answer 22

Before 30yrs

Question 23

What is a stacked arrangement of two rows of elongated palisading nuclei that alternates with acellular zones made up of cytoplasmic processes?
In which tumor is this seen?
A. Schwannoma
B. Neurofibroma
C. Both
D. None of the above

Answer 23

Verocay body

C. Seen in both schwannoma and neurofibroma

Question 24

A polymorphism in this gene is seen in almost 90% of patients with the Sturge-Weber trait and a similar # of patients with non-syndromic port-wine stains on the cranium

Answer 24

GNAQ

Question 25

Whitish, marble-like appearance of the putamen, thalamus and border zones of the cerebral cortex that is the most frequent pathologic finding in the brain after insult to the infant brain

Answer 25

Status marmoratus or état marbré

Whitish strands - nerve cell loss and gliosis
Condensation - bands of traversing myelinated fibers

Question 26

Pathologic changes of symmetrically distributed nerve cell loss and gliosis and unique yellow staining of nuclear masses from hyperbilirubinemia in kernicterus spare the what areas?

Answer 26

Hippocampus

Immature cerebral cortex

Question 27

Target serum bilirubin level in the treatment of erythroblastosis fetalis that would allow the nervous system to escape perinatal damage

Answer 27

Keep blood bilirubin to less than 20mg/dL in term infants, <10mg/dL in premature infants

Question 28

Until this age of gestation, large microbial organisms such as bacteria, spirochetes, protozoa, fungi, are unable to invade the embryo

Answer 28

3rd - 4th month of gestation

Question 29

Times the ff organisms are able to invade the developing embryo
A. Rubella
B. CMV
C. HIV
D. HSV2
E. Treponema pallidum 
F. Toxoplasma
G. Listeria monocytogenes

Answer 29

A. Rubella - first 10wks AOG (up to 24th wk AOG)
B. CMV - 1st trimester, during delivery, breastfeeding
C. HIV - 1st trimester, during delivery, breastfeeding
D. HSV2 - during delivery
E. Treponema pallidum - 4th to 7th mos AOG
F. Toxoplasma - late in the gestational period
G. Listeria monocytogenes - during delivery or in utero from maternal and fetal septicemia

Question 30

What drug may be used to prevent fetal infection from mothers who develop toxoplasma antibodies in the first 2-3 mos of pregnancy?
Once fetus is infected, what drug should be used?

Answer 30

Spiramycin (Rovamycine)

If fetus infected - use pyrimethamine and sulfadiazine

Question 31

Cerebral calcifications are present mainly in both Congenital Toxoplasmosis and CMV infections, how can the two be differentiated on imaging?

Answer 31

Toxoplasma- widely disseminated cerebral calcifications

CMV - calcifications are periventricular

Question 32

Pregnant mothers with syphilis must be treated before what month to prevent infection of the fetus?

Answer 32

Before the 4th month AOG

Transmission occurs at any time from the 4th to 7th months

Question 33

In which congenital viral infection can a second child be infected?

Answer 33

CMV

Question 34

Genetic abnormality in the Fragile X syndrome

Answer 34

Unstable inherited CGG repeating sequence at the distal end of the long arm of the X chromosome

Question 35

The Fragile X premutation syndrome may be manifest in adult women as

Answer 35

Premature ovrian failure