Peds Flashcards
A patient who has tuberous sclerosis is most likely to have a mutation in which of the following
genes?
A. MLH1
B. VHL
C. PTCH1
D. NF1
E. TSC2
TSC2
TSC1 and TSC2 are mutations associated with tuberous sclerosis that result in constitutively active
mTOR signaling. The other genes provided lead to other genetic conditions associated with benign
brain tumors: NF1 – neurofibromatosis, MLH-1 - Turcot syndrome, VHL - von Hippel-Lindau
syndrome, PTCH1 – Gorlin syndrome.
Infants should reach the developmental milestones of pulling up to a stand and cruising (walking while holding onto furniture) by which of the following months of age?
A. 9 months
B. 12 months
C. 18 months
D. 6 months
E. 24 months
12 months
While early developmental milestones are variable from child to child, the clinician should be
aware of when most children reach a milestone to watch for gross motor delay. Some infants may
be able to pull to a stand as early as 9 months of age, but most infants should be able to perform
this task by age 12 months.
A 6-month-old would be expected to be able to roll over.
A 9-month-old would be expected to crawl.
An 18-month-old would be expected to be able to walk alone and should be saying several
individual words.
A 24-month-old would be expected to be able to engage in parallel play and speak in 2 to 4 word
sentences
Which of the following characteristics of leukodystrophies differentiate them from demyelinating
diseases?
A. Demyelinating diseases do not present in childhood whereas leukodystrophies present
early in life
B. Leukodystrophies are always progressive and fatal in childhood whereas demyelinating
disorders are not
C. Leukodystrophies usually respond to steroid medications whereas demyelinating diseases
usually do not
D. Leukodystrophies are inherited whereas most demyelinating diseases are not heritable
E. Leukodystrophies feature dysmyelination but not demyelination
Leukodystrophies are inherited whereas most demyelinating diseases are not heritable
Disorders of myelin fall into three broad categories: hypomyelination (a deficient quantity of
myelin), dysmyelination (abnormal myelin deposition), and demyelination (myelin was formed
adequately but is then broken down or damaged). Leukodystrophies are a heterogenous group of
more than 50 disorders, some of which feature all three types of myelin problem listed above, but
all of which are genetic in etiology. The majority of purely demyelinating diseases, including
multiple sclerosis, transverse myelitis, etc. are acquired, with the exception being the peripheral
demyelination seen in Charcot-Marie-Tooth disease. This makes “Leukodystrophies are inherited
whereas most demyelinating diseases are not heritable” the correct answer.
“Leukodystrophies feature dysmyelination but not demyelination” is incorrect for reasons noted
above. Many leukodystrophies cause both dysmyelination and demyelination.
Most leukodystrophies do present within the first few years of life, but some do not present until
adulthood. Similarly, while many demyelinating conditions strike adults, they can present in
childhood, including multiple sclerosis, neuromyelitis optica, and transverse myelitis. Therefore
“Demyelinating diseases do not present in childhood whereas leukodystrophies present early in
life” is incorrect.
Steroid medications are commonly used in some demyelinating diseases but are not frequently
used in leukodystrophies, making “Leukodystrophies usually respond to steroid medications
whereas demyelinating diseases usually do not” an incorrect choice.
For reasons already described, “Leukodystrophies are always progressive and fatal in childhood
whereas demyelinating diseases are not” cannot be correct
Which of the following is the most likely congenital spinal malformation in the patient with the lumbar lesion shown?
A. Thickened filum terminale
B. Diastematomyelia
C. Syringomyelia
D. Hemivertebra
E. Lipomyelomeningocele
Diastematomyelia
Cutaneous midline findings are an important screening tool for potential underlying spinal
dysraphism. In this case, focal hypertrichosis is frequently associated with diastematomyelia. Two
thirds of cases of diastematomyelia have some sort of cutaneous finding including hypertrichosis,
dimples, hemangiomas, or lipomas. The pathophysiology of these associated cutaneous findings
is not completely understood. Lipomyelomeningoceles are often associated with cutaneous
lipomas. Thickened filum terminale, syringomyelia, and hemivertebrae may or may not be
associated with cutaneous findings
The maternal disorder most commonly responsible for sacral agenesis in newborn infants is
A. Maternal Diabetes
B. Chronic Obstructive Pulmonary Disease (COPD)
C. Urinary Tract Infection
D. Hypertension
E. Epilepsy
Maternal Diabetes
Based on results from the National Birth Defects Prevention Study (NBDPS) and multiple other
published clinical reviews, maternal diabetes represents the most common reported risk factor for
sacral agenesis. While both Type I and Type II diabetes represent risk factors, pre-existing
maternal Type I diabetes represents the strongest risk factor for sacral agenesis. Additional risk
factors include multiparity and periconceptional smoking in mothers without preexisting diabetes.
With a live birth incidence of 2.6/100,000, non-syndromic sacral agenesis represents a rare
congenital disorder involving full or partial absence of the sacrum due to an embryologic insult
prior to the 4th week of gestation. Resulting from incomplete formation of the caudal mesoderm,
sacral agenesis frequently co-presents with other gastrointestinal, genitourinary, cardiac,
musculoskeletal, and central nervous system defects. Common syndromic associations with
sacral agenesis include: OEIS (Omphalocele, Exstrophy of the cloaca, Imperforate anus, Spinal
defects), Currarino triad (autosomal dominant condition involving pre-sacral mass, anorectal
malformation, and sacral defects), and VATER/VACTERL complex (Vertebral anomalies, Anorectal
malformations, Cardiac defects, Tracheoesophageal fistula, Esophageal atresia, Renal
abnormalities, and Limb defects). Sacral agenesis may lead to motor dysfunction and urological
abnormalities including urinary incontinence and recurrent urinary tract infections. Based on
multiple clinical reviews and NBDPS data, maternal diabetes accounts for up to 40% of newborn
infant sacral agenesis cases with a reported odds ratio exceeding 100. Pre-conceptional
improvements in glycemic control may reduce the incidence of congenital anomalies, including
sacral agenesis.
While maternal use of anti-epileptic drugs (AEDs) has been suspected as a potential risk factor for
sacral agenesis based on historic case reports, epilepsy has not been defined as a common risk
factor for non-syndromic sacral agenesis. Similarly, while maternal use of diuretics had been
studied in historic case reports, hypertension has not been identified as a risk factor for sacral
agenesis. Among women without diabetes, periconceptional smoking represents a risk factor for
sacral agenesis—highlighting the importance of smoking cessation counseling during pregnancy
planning. However, these associations do not implicate maternal COPD as a common risk factor
for sacral agenesis. In the analysis of NBDPS data, investigation of peri-conceptional urinary tract
infections among mothers without diabetes showed a weak positive association with sacral
agenesis that did not remain significant in multivariable analysis
Focal cortical dysplasia type IIb is characterized by a good prognosis for seizure freedom after
total resection of dysplastic tissue. Which of the following is the defining pathologic characteristic
of this type of dysplasia?
A. Epilepsy in the setting of cortical dysplasia with eosinophilic balloon cells
B. Aberrant radial or tangential cortical lamination
C. Cortical dyslamination and dysmorphic neurons without balloon cells
D. Rounded oligodendroglial-like cells intermixed with dysmorphic ganglion cells
E. Cortical dyslamination with hippocampal sclerosis
Epilepsy in the setting of cortical dysplasia with eosinophilic balloon cells
Focal cortical dysplasias (FCDs) are localized regions of malformed cerebral cortex frequently
associated with epilepsy. Various classification systems have been introduced, but updated
variants have been classified into Types I (a-c), II (a & b), and III (a-d).
Type I lesions have focal cortical dysplasia with abnormal radial cortical lamination (Ia), abnormal
tangential cortical lamination (Ib), or both (Ic). Thus, answer choice B defines these types of type I
lesions.
Type II lesions include dysmorphic lesions in the presence or absence of balloon cells. Balloon
cells strictly define type IIb lesions and are not found in other FCD lesions. Balloon cells have a
large cell body with glassy eosinophilic cytoplasm which lacks Nissl substance. Multiple nuclei
may be present and small nuclei may be joined by nuclear “bridges.” They may be found in any
cortical location and have morphological similarities to both giant cells and cortical tubers.
Type III lesions refer to cortical lamination abnormalities that are associated with another
pathological lesion. These variants include hippocampal atrophy/sclerosis (IIIa), tumors (IIIb),
vascular malformations (IIIc), and other early childhood lesions (IIId).
Crouzon’s disease and Apert syndrome have which of the following findings in common?
A. Bi-coronal craniosynostosis with brachycephaly
B. Sagittal craniosynostosis with scaphocephaly
C. Syndactyly of hands and feet
D. Broad based thumbs and hallux
E. Neurocognitive impairments
Bi-coronal craniosynostosis with brachycephaly
Bi-coronal craniosynostosis resulting in brachycephaly is a common type of syndromic
craniosynostosis present in both Crouzon’s disease and Apert syndrome. Other features common
to both Crouzon’s disease and Apert syndrome include hypertelorism, ocular proptosis, fusion of
cervical vertebrae (typically C2-C3 in Crouzon’s disease and C5-C6 in Apert syndrome), and
midface (maxillary) hypoplasia.
Both Crouzon’s disease and Apert syndrome may result from autosomal dominant (or sporadic)
transmission and most commonly involve genetic mutations of the fibroblast growth factor receptor
2 (FGFR2) locus. Mutations in the FGFR1 genetic locus are more commonly associated with
Pfeiffer Syndrome, while mutations in the FGFR3 locus occur with Muenke syndrome, Crouzon’s
disease, and achondroplasia. Autosomal recessive inheritance occurs less commonly among the
types of syndromic craniosynostosis, specifically with Carpenter syndrome.
Sagittal synostosis with scaphocephaly most commonly presents as isolated non-syndromic
craniosynostosis but may co-present in multi-suture craniosynostosis and has been described in
Crouzon’s disease. Syndactyly of hands and feet represents an important identifying feature in
patients with Apert syndrome but is absent in Crouzon’s disease. Broad based thumbs and hallux
are features of Pfeiffer’s syndrome. Developmental delay and neurocognitive impairments are
more commonly associated with Apert syndrome but are not typical in Crouzon’s disease.
The lesion in the image shown is most likely which of the following?
A. Craniofacial polyp
B. Nasal Dermoid
C. Congenital lesion
D. Frontoethmoidal encephalocele
E. Sinus Tract
Nasal Dermoid
Nasal dermoid cysts are rare lesions that present in one out of 20,000 to 40,000 births. They arise
from the ectoderm and mesoderm and are lined by stratified squamous epithelium. They can
additionally contain more adnexal structures and sebaceous tissue. Typically, dermoid cysts can
be associated with other midline defects. Clinically, patients may present with a midline mass or
swelling at the nasal dorsum or an associated pit. Superimposed infections may occur, which can
complicate treatment as they can cause osteomyelitis, meningitis or cerebral abscess. Treatment
is aimed at complete resection, as residual lesion or associated tract can contribute to future
infections or regrowth.
While it is true that a nasal dermoid cyst is a congenital lesion, this is not the best answer as it is
too general and there is a more specific answer for the question.
Nasal dermoid cysts may consist of a sinus tract that extends to the skull base. However, this is
typically associated with a pit or open tract and may be associated with drainage.
Encephaloceles that extend through the front of the skull are referred to as frontoethmoidal
encephaloceles. Anterior encephaloceles are rare lesions more commonly found in parts of
southeast Asia. These may extend through the frontal bones but can also extend through the
nasopharynx or frontobasal regions. While there is a protuberance along the dorsal aspect of the
nose, there is a pearlescent sheen that is characteristic for dermoids. Encephaloceles may have
more of a prominence with a thicker layer of dermal coverage. MRI and/or CT will definitively
distinguish the two.
Nasal polyps are often found within the nares and not extending out along the dorsum of the nasal
bridge.
A 3-month-old girl is brought to the clinic because her parents are concerned about the shape of her head. She is otherwise healthy with a normal prenatal and perinatal history. They noticed some asymmetry soon after birth, and it has become more noticeable during the past few weeks. A
photograph is shown. Which of the following is the most likely diagnosis?
A. Positional plagiocephaly
B. Trigonocephaly
C. Brachycephaly
D. Scaphocephaly
E. Lambdoid synostosis
Positional plagiocephaly
The photo shows a child with right occipital flattening. Positional plagiocephaly is the most
common cause and should be differentiated from unilateral lambdoid synostosis. Patients with
positional plagiocephaly tend to have a parallelogram-shaped head with the ipsilateral ear
translated anteriorly and ipsilateral compensatory frontal bossing.
By contrast, patients with lambdoid synostosis will have a trapezoid-shaped head when viewed
from above. The ipsilateral ear will be pulled more posteriorly and there is typically an ipsilateral
mastoid bulge.
Trigonocephaly describes the head shape associated with metopic synostosis, in which patients
present with a triangle forehead shape, hypotelorism, pterional restriction and biparietal widening.
Brachycephaly describes the head shape associated with bilateral coronal synostosis, resulting in
forehead flattening, elevation of the lateral orbital rims and a shortened AP skull dimension.
Scaphocephaly describes the head shape associated with sagittal synostosis. Also referred to as
dolichocephaly, these patients have an elongated head shape, compensatory frontal and/or
occipital bossing, and narrowing of the skull.
A photomicrograph of a biopsy specimen stained with hematoxylin and eosin is shown. The histopathologic features of nuclear pleomorphism, geographic necrosis, hypercellularity, microvascular proliferation, and reticulin staining are most commonly associated with which of the following neoplasms?
A. Pituitary adenoma
B. Retinoblastoma C. Astrocytoma
D. Ependymoma
E. Gliosarcoma
Gliosarcoma
Gliosarcomas demonstrate a component resembling astrocytomas and mesenchymal sarcoma. Tumors are highly cellular, show areas of necrosis, and microvascular proliferation. Patches of reticulin staining are seen in contrast to astrocytomas. In pituitary adenomas, reticulin staining is lost in contrast to the normal pituitary gland.
Which of the following is sometimes a complication of Paget’s disease of bone?
A. Ischemic complications
B. Osteochondroma
C. Loss of olfaction
D. Optic nerve compression
E. Facial numbness
Optic nerve compression
Fibrous dysplasia (FD) is the 2nd most common bone remodeling disorder after osteoporosis with a incidence of 1-2% in adults >55 years of age. FD results from increased osteoclast bone resorption with disorganized, woven bone formation and hypervascularity. Disruption of RANK/RANK ligand signaling can result in FD, and environmental factors have also been suggested as contributors. Neurosurgical manifestations of FD include optic nerve compression, headache, cranial nerve deficits, basilar invagination, spinal stenosis, hydrocephalus, and peripheral neuropathy. These findings have been suggested as a result of bony compression; however non-compressive optic neuropathy and cranial nerve deficits as well as a higher likelihood of dementia and epilepsy in Paget disease suggests the potential of a somatic mutation pattern impacting multiple cell types.
A 45-year-old man is referred for evaluation because of headache and a small cerebellar arteriovenous malformation. He has a blanching red spot on his cheek, anemia, and frequent nosebleeds. Which of the following is the most likely diagnosis?
A. Tuberous Sclerosis
B. von Hippel-Lindau Disease
C. Sturge-Weber Syndrome
D. Hereditary Hemorrhagic Telangiectasia E. Gorlin Syndrome
Hereditary Hemorrhagic Telangiectasia
This is a textbook description of the findings of Hereditary Hemorrhagic Telangiectasia (HHT). HHT, also called Osler-Weber-Rendu disease, is an autosomal dominant inherited disorder associated with multiple genes. Common findings in HHT include small arteriovenous malformations in the nose, brain, liver, and lungs. There can be capillary telangiectasias in the face, fingers, and mucosal surfaces. Anemia is common due to bleeding from frequent epistaxis or from GI bleeding, which may be undetectable to the patient. Most patients present with frequent nosebleeds by age 45. The other answer choices are not consistent with this clinical presentation.
Infants generally reach the developmental milestone of parallel play at which of the following months of age?
A. 24
B. 48
C. 42
D. 18
E. 32
**24
**
Developmental milestones are predictable stages in the course of neurocognitive maturation in children that track social/emotional, motor, cognitive, and speech development. Significant deviations from the expected developmental course could be an indication of underlying pathology. Parallel play is a developmental milestone in the social/emotional scale that describes children interacting and participating in activities side by side with other children, but without cooperation on a similar task. Typically this type of play is observed around 2 years old. Prior to this, around 18 months, children play with objects more independently with minimal interaction or acknowledgement of peers. By 3 years of age, children’s imagination tends to develop, which may be incorporated into more social and communicative interactions with their peers.
During the past 20 years, which of the following has had the single largest effect on the decreased incidence of myelomeningocele in the US?
A. Niacin supplementation
B. Vitamin D supplementation
C. Iron supplementation
D. Vitamin K supplementation
E. Folate supplementation
Folate supplementation
Most isolated NTDs appear to be caused by folate deficiency (“folate sensitive” NTDs), likely in
combination with genetic or other environmental risk factors. Periconceptional folic acid supplementation, food fortification with folic acid, and prenatal screening for open NTDs combined with access to pregnancy termination have led to a dramatic decrease in the prevalence of open NTDs at birth where these interventions are applied. For women with no previously affected pregnancy, daily folic acid supplementation (alone or in combination with other vitamins and minerals) reduced NTDs by 93 percent compared with no interventions/placebo or vitamins and minerals without folic acid. Rates of NTDs have declined where prenatal maternal serum screening programs for alpha fetoprotein and periconceptional folic acid supplementation and food fortification (instituted in the 1990s) are practiced.
Which of the following substances accumulates in neural tissue in association with metachromatic leukodystrophy?
A. Sulfatides
B. Ceramide-Trihexoside
C. Sphingomyelin
D. GM2-gangliosides
E. Glucocerebroside
Sulfatides
Sulfatides accumulate in the cells of patients affected with metachromatic leukodystrophy. Metachromatic leukodystrophy is an autosomal recessive disorder affecting the metabolism of sphingolipids. Sphingolipids are important components of the plasma membrane that play a role in signal transduction and cellular recognition, especially in cells of the nervous system. They are continuously synthesized and degraded. Degradation occurs in lysosomes. Metachromatic leukodystrophy results from a mutation in the gene encoding Arylsulfatase A. This is a lysosomal enzyme responsible for the desulfation of cerebroside sulfate, a sulfatide that is an important glycolipid of myelin. When Arylsulfatase A activity is reduced, this results in the accumulation of sulfatides, especially cerebroside sulfate, in the lysosomes of neurons. The accumulation of cerebroside sulfate destroys oligodendroglial and Schwann cells, causing central and peripheral demyelination.
Sphingomyelin accumulates in the cells of patients affected with Niemann-Pick disease due to deficiency in the enzyme sphingomyelinase. Glucocerebroside accumulate in the cells of patients with Gaucher disease as a result of deficiency in the enzyme Glucocerebrosidase. GM2- gangliosides accumulate in the cells of patients with Tay-Sachs disease as a result of a deficiency in the enzyme Hexosaminidase-A. Ceramide-Trihexoside accumulates in the cells of patients with Fabry disease as a result of deficiency in the enzyme α-galactosidase A.
A dietary deficiency of which of the following is an environmental risk factor for the development of myelomeningocele?
A. Vitamin B2
B. Vitamin B6
C. Vitamin B7
D. Vitamin B1
E. Vitamin B9
Vitamin B9
Deficiency of maternal dietary folic acid, or vitamin B9, has been shown to correlate with the development of anencephaly and myelomeningocele, and subsequent dietary supplementation has decreased the incidence of these birth defects in the general population. It is thought that folic acid plays a key role in methylation of proteins, lipids and myelin, and if this is impaired, proper closure of the neural tube will be affected.
Vitamin B12 is cobalamin, and its dietary deficiency has more recently been associated with neural tube defects as well as an important part of the methylation pathway. Vitamin B6 is pyridoxine, B1 is thiamin, B7 is biotin, B2 is riboflavin, none of which have had dietary deficiencies correlated with the development of myelomeningoceles.
A 66-year-old woman is evaluated because of a six-month history of progressive neck and back pain. Based on the CT myelogram of the mid-thoracic region and the photomicrographs (H & E stains [left = low power, right = high power]) shown, which of the following is the most likely diagnosis?
A. Meningeal Cyst
B. Perineural (Tarlov) Cyst
C. Arachnoid Cyst
D. Epidermoid/Dermoid Cyst
E. Neurenteric Cyst
Arachnoid Cyst
The CT myelogram (figure 1, top panels) demonstrates an intradural extramedullary lesion with homogenous contrast uptake causing compression and anterior displacement of the spinal cord There is focal displacement or buckling (classic pathognomonic ‘scalpel sign’ described in the literature) near the superior aspect of the imaging region shown. These imaging findings coupled with the photomicrographs (H & E Stains) that suggest thin connective tissue with meningothelial cells and bland inner contents solidify the diagnosis of spinal arachnoid cyst. Additionally, a dorsal thoracic arachnoid cyst matches the common location reported in published literature.
Intradural spinal arachnoid cysts are classified as primary (idiopathic) or secondary when resulting after trauma, infection, surgery, or hemorrhage. Most reported spinal arachnoid cysts occur in the dorsal midline thoracic spine. Common presenting symptoms occur due to thoracic spinal cord compression and include back pain, myelopathy, gait disturbance, neuropathic pain, parasthesias, and motor weakness. Spinal arachnoid cysts may be associated with a spinal cord syrinx in a minority of cases. Surgery involving resection, fenestration/marsupialization, or shunting of the spinal arachnoid cyst typically results in improvement of gait, motor, and sensory symptoms, though with resolution of neuropathic pain in fewer patients. Surgery typically yields syrinx resolution or reduction in a majority of patients.
Meningeal cysts typically are epidural, which is not supported by the CT myelogram, though the H & E Stains could be confused for dura-like collagen and inner arachnoid layer. An epidermoid/dermoid cyst would not exhibit homogenous contrast uptake or enhancement and would have a different appearance on H & E Stains, with keratin, squamous epithelium, and possible hair follicles or sebaceous glands (dermoid cyst). Neurenteric cysts typically invade the spinal canal anteriorly through a vertebral column defect while representative H & E Staining would show columnar epithelium. Finally, a perineural (Tarlov) cyst would present along a nerve root or dorsal root ganglion in the sacral region.
A 39-year-old man is evaluated because of a three-month history of ataxia and loss of strength and dexterity in his left hand. Family history is unremarkable. MR images of the brain and spine are shown. This patient is most likely to harbor which of the following comorbid conditions?
A. Cardiac rhabdomyoma
B. Pancreatic tumor
C. Hepatic hemangioma
D. Lymphoma
E. Ovarian cyst
**Pancreatic tumor
**
Von Hippel-Lindau (VHL) syndrome is an autosomal dominant neoplasia syndrome that results from a germline mutation of the VHL gene on chromosome 3. Central nervous system (CNS) manifestations include cranial, spinal, and retinal hemangioblastomas as well as endolymphatic sac tumors. Visceral conditions associated with VHL include renal cysts, renal carcinoma, pancreatic cysts, pancreatic neuroendocrine tumors, and pheochromocytomas. Patients with a family history of VHL and one manifestation are diagnosed with the disease. However, about twenty percent of VHL patients do not have a family history; in these patients, clinical diagnosis is made if the patient has two or more CNS hemangioblastomas or one CNS hemangioblastoma and a VHL-associated visceral tumor.
A healthy 14-month-old girl is evaluated for the head growth curve shown (Figure 1). An MR image is also shown (Figure 2). Which of the following is the most appropriate clinical course of action?
A. Ophthalmology consult
B. Skeletal Survey
C. CSF drainage
D. MRI Brain with and without contrast
E. Obtain family history, parental and sibling head circumferences
Obtain family history, parental and sibling head circumferences
The T2 weighted MRI reveals benign external subarachnoid spaces of infancy, or BESSI. This is evidenced by the increased T2 signal in the subarachnoid space as defined by the presence of cortical vessels and is most commonly seen over the frontal and temporal convexities. There may be associated mild ventriculomegaly. The growth chart reveals that the child’s head is macrocephalic (more than 2 standard deviations above the curve for age, sex and body size) and accelerating. BESSI is the most common cause of macrocephaly in infants, and is thought to have a genetic predisposition as a primary relative or paternal relative may also have a large head. This can be confirmed by measuring parents’ head sizes. It is thought to be due to delayed maturation of arachnoid villi. Children with BESSI may show an expansion of head growth between 3-12 months of age without symptoms of hydrocephalus or elevated intracranial pressure, but will typically decelerate by 18-24 months of age and remain with a larger than average head.
BESSI must be distinguished from other pathologic forms of macrocephaly including hydrocephalus, where CSF diversion may be indicated, or obstructive pathologies which may be better elucidated with a contrast-enhanced brain MRI. Determining the location of the fluid to be in the subarachnoid space (versus the subdural space is also important in ruling out a traumatic injury, in which case a skeletal survey for further non-accidental trauma workup may be initiated. Ophthalmologic exam is important to evaluate for retinal hemorrhages (a sign of trauma) and papilledema (a sign of increased intracranial pressure) if either of these more pathologic etiologies are suspected based on imaging and history and exam.
The tumor excision specimen in the photomicrograph shown is from a 14-year-old boy who had a third ventricle tumor. The most likely diagnosis is
A. Astrocytoma
B. Teratoma
C. Retinoblastoma
D. Ependymoma
E. Subependymoma
Teratoma
Teratomas are heterogenous germ cell tumors with endodermal, mesodermal and ectodermal components that occur along the midline. A workup including alpha fetoprotein, human chorionic gonadotropin, and alkaline phosphatase is indicated as teratomas can be mixed with other germ cell type tumors. These lesions commonly occur in children. Subependymal giant cell astrocytomas are other third ventricle tumors that occur in tuberous sclerosis. Subependymomas are more common in elderly patients. Ependymomas more commonly arise from the 4th ventricle in children.
Which of the following substances accumulates in association with Tay-Sachs disease?
A. Sulfatides
B. Glucocerebroside
C. GM2-gangliosides
D. Ceramide Trihexoside
E. Sphingomyelin
GM2-gangliosides
GM2 gangliosides accumulate in the cells of patients with Tay-Sachs disease. Tay-Sachs disease is an autosomal recessive progressive neurodegenerative disorder. While rare, it is more common among people of Ashkenazi Jewish descent. This disease alters the metabolism of sphingolipids.
Sphingolipids are important components of the plasma membrane, affecting signal transduction and cellular recognition, particularly in cells of the nervous system. They are continuously synthesized and degraded. This degradation occurs in lysosomes. Tay-Sachs disease results from mutation in the HEXA gene on chromosome 15. The HEXA gene encodes the enzyme hexosaminidase-A. Hexosaminidase-A is a hydrolytic lysosomal enzyme that is important in the metabolism of specific sphingolipids, the gangliosides, to ceramides. It hydrolyzes GM2 gangliosides into GM3 gangliosides. When hexosaminidase-A activity is reduced, this results in the accumulation of its substrate GM2 gangliosides in the lysosomes of neurons, resulting in cellular toxicity and death. This leads to developmental disability and progressive lethal neurodegeneration.
Sphingomyelin accumulates in cells of patients affected with Niemann-Pick disease due to deficiency in the enzyme sphingomyelinase. Glucocerebroside accumulate in the cells of patients with Gaucher disease as a result of deficiency in the enzyme Glucocerebrosidase. Sulfatides accumulate in the cells of patients with metachromatic leukodystrophy as a result of deficiency in the enzyme Arylsulfatase A. Ceramide-Trihexoside accumulates in the cells of patients with Fabry disease as a result of deficiency in the enzyme α-galactosidase A.
