Genetic Syndromes

Question 1

X-linked recessive muscular dystrophy –> slowly progressing muscular weakness in the legs and pelvis, later in life (pre-teens), no cognitive impairments of myopathy

Answer 1

Becker muscular dystrophy

Question 2

X-linked recessive with an absence of dystrophin, and starts in childhood at around 2 to 6 years of age; 20-50% of children have cognitive impairment

Answer 2

Duchenne muscular dystrophy

Question 3

Caused by expansion of GAA, and results in cerebellar degeneration and gait disturbance; peak onset is 10-13; also results in hearing loss, dysarthria, and cognitive deficits

Answer 3

Friedreich’s ataxia

Question 4

Multi-systemic disease that affects mainly adults, and results in wasting of the muscles, cataracts, heart conduction defects, endocrine changes, and myotonia

Answer 4

Myotonic dystrophy

Question 5

X-linked recessive (ABCD1 gene); abnormal protein in peroxisome, responsible for breaking down long chain fatty acids

Answer 5

Adrenoleukodystrophy

Question 6

X-linked recessive; affects males –> spastic paresis, neuropathy, dementia; adrenal insufficiency common (low sodium, high potassium, low cortisol)

Answer 6

Adrenoleukodystrophy

Question 7

___ is an autosomal recessive lysosomal storage disease; deficiency of aryl sulfatase A deficiency –> muscle wasting, seizures, developmental delays, blindness and swallowing difficulties in children and dementia in adults.

Answer 7

Metachromatic leukodystrophy

Question 8

___ is a lysosomal storage disease; autosomal recessive –> neurological deficits including seizures, swallowing difficulties and developmental delays

Answer 8

Krabbe disease

Question 9

W/o treatment with a special low-phenylalanine diet, these children with ___ develop permanent intellectual disability-seizures, delayed development, behavioral problems, and psychiatric disorders are also common

Answer 9

Phenylketonuria

Question 10

Neurological manifestations include chorea, dementia, ataxia, axonal neuropathy and seizures. CK levels and sometimes hepatic transaminases may be increased

Answer 10

Neuroacanthocytosis

Question 11

Clinical triad of ___ is intellectual disability, seizures, and hamartomas

Answer 11

Tuberous sclerosis

Question 12

Stiff Person Syndrome is associated w/ ___ antibodies; p/w progressive fluctuating muscular rigidity. Typically the rigidity affects the axial muscles of the back, abdomen, hips, and shoulders

Answer 12

Anti- glutamic acid decarboxylase (GAD) antibodies

Question 13

“With ___, the child develops normally for the first 5 months (or so) of his/her life. Then, sometime between 6 months and 4 years of age, the child loses social and communication skills. The child is often left with ““profoundly impaired expressive and receptive language.”””

Answer 13

Rett syndrome

Question 14

In ___ the first clue in an infant is often the presence of seizures, delayed development or white patches on the skin. Between 25% and 61% of affected individuals meet the diagnostic criteria for autism spectrum disorder

Answer 14

Tuberous sclerosis

Question 15

___ is a genetic disorder where the child tends to also have poor language skills; the child is very friendly and often trusts strangers.

Answer 15

Williams syndrome

Question 16

___ is an X-linked dominant (lethal in males) syndrome characterized by agenesis of the corpus callosum, developmental delay, and infantile spasms. Associated features may include colobomas of the eye or microphthalmia.

Answer 16

Aicardi syndrome

Question 17

___ is an X-Linked lysosomal storage disease that causes cardiomyopathy, skin lesions and renal failure; deficiency in ___

Answer 17

Fabry’s disease; a-galactosidase A

Question 18

___ occurs in girls between 6 and 18 months of age, is characterized by loss of milestones and decrease in head circumference. It is believed to be caused by mutation in the MECP2 gene.

Answer 18

Rett syndrome

Question 19

___ is an X-linked recessive condition that is caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase

Answer 19

Lesch Nyhan syndrome

Question 20

Wilson disease, an autosomal recessive disorder due to a mutation in the ATP7B gene. In Wilson’s disease, excessive amounts of copper accumulate in the body, particularly in the liver, brain, and eyes. On lab values, it is characterized by ___

Answer 20

low serum ceruloplasmin, low serum copper and high urine copper levels

Question 21

___ is a rare neurological condition of unknown etiology that begins in childhood or adolescence and is characterized by episodes of hypersomnolence and altered behaviors during wakefulness

Answer 21

Kleine-Levin syndrome

Question 22

Creutzfeldt-Jakob disease classically shows ___ on EEG and is positive for ___ in the CSF fluid

Answer 22

periodic sharp wave complexes; specific protein 14-3-3

Question 23

___ is caused by mutations in the gene MECP2 located on the X chromosome and can arise sporadically or from germline mutations. MECP2 codes for the protein methyl cytosine binding protein 2 (MeCBP2)

Answer 23

Rett syndrome

Question 24

___ is characterized by non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs, and skin. Symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, and lung and kidney disease

Answer 24

Tuberous sclerosis

Question 25

___ is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin, respectively

Answer 25

Tuberous sclerosis

Question 26

___ is a severe childhood-onset epilepsy. It is characterized by multiple and concurrent seizure types, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG)

Answer 26

Lennox- Gastaut

Question 27

___ is characterized by developmental disability and intellectual disability, maternal gene deleted and, paternal turned off by genetic imprinting

Answer 27

Angelman Syndrome Chrom 15

Question 28

___ is an autosomal recessive glycogen storage disease caused by a deficiency in lysosomal alpha-glucosidase, which normally participates in the metabolism of glycogen into glucose. Adults suffer from a slowly progressive myopathy with respiratory failure

Answer 28

Acid maltase deficiency

Question 29

A 3-year-old child had normal delivery, poor language development, and normal head circumference. In prekindergarten, the caretaker started to notice stereotypic hand wringing movements. The child's head growth has decelerated, and purposeful hand movement has been lost. What is dx?

Answer 29

Rett Syndrome

Question 30

___ may involve episodic hyperphagia, hypersomnia and hypersexuality

Answer 30

Klein-Levin syndrome

Question 31

___ is a condition is characterized by the 4 D's: dysmnesia (impaired recall that is improved with cuing), dysexecutive syndrome, delay (slowness), and depletion (apathy and amotivation)

Answer 31

Binswanger's disease Binswanger's Disease is a rare form of dementia sometimes referred to as subcortical vascular dementia. People who have Binswanger's Disease typically have developed a narrowing of the arteries which then restricts blood flow in the brain. In the past, this was commonly referred to as "hardening of the arteries.

Question 32

Juvenile Huntington's disease is a rare disorder occurring before the age of twenty years. Neurocognitive disorder due to Huntington's disease comprises rapidly progressive cognitive decline with aggressive behavior, inattention, impaired memory and learning, and motor and mood disturbances. Unlike adult-onset Huntington's disease which presents with chorea, juvenile Huntington's disease much more commonly presents with ___. Huntington's disease is always transmitted as ___

Answer 32

dystonia and seizures; an autosomal dominant trait from either parent, but more often paternal

Question 33

___ typically presents with enlarged hands and feet. Enlargement of the forehead, jaw, and nose is also observed. That is why patients occasionally complain of their hats getting tight. The disorder is due to excess growth hormone production from the pituitary gland, most of the times it is due to the presence of a benign tumor, known as a pituitary adenoma.

Answer 33

Acromegaly

Question 34

The clinical features include hypertonia, horseshoe kidney, smallmouth, micrognathia, pointy ears, short sternum, prominent occiput and flexed fingers with the index finger overlapping the third finger and the fifth finger overlapping the fourth.

Answer 34

Edwards syndrome - Trisomy 18

Question 35

___ is autosomal dominant d/o that p/w seizures, mental retardation, and behavioral problems. Cutaneous lesions include ash leaf spot, adenoma sebaceum, and shagreen spots. Can also have retinal hamartomas

Answer 35

Tuberous sclerosis

Question 36

___ is pervasive developmental d/o seen only in girls, involves deceleration of head growth from ages 5months-4yrs, loss of purposeful hand skills, development of stereotyped hand movements between ages 5mo-2.5yrs, loss of social engagement, impairment in expressive and receptive language

Answer 36

Rett's Disorder

Question 37

___ results from missing sex chromosome, XO. Patient is female with no secondary sex characteristics and an absence or minimal development of gonads. Webbed neck and kidney anomalies

Answer 37

Turner's Syndrome

Question 38

___ results from prescence of exta chromosome --> XXY. Pt has male habitus bc of Y chromosome but bc of extra X, they do not develop strong male characteristics. They are infertile and can develop breast tissue during adolesence. can p/w mild MR, obesity, small penis/scrotum

Answer 38

Klinefelter's Syndrome

Question 39

___ results from expansion of trinucleotide repeat sequences at chromosome 4p16.3

Answer 39

Huntington's Disease

Question 40

Short palpebral fissures are found in children with ___

Answer 40

Fetal Alcohol Syndrome

Question 41

Kid presents with mental retardation, long ears, narrow face, short stature, hyperextendable joints, arched palate, macro-orchidism, seizures, and autistic features. High rate of ADHD and learning disorders

Answer 41

Fragile X Syndrome

Question 42

Pt p/w hx of wing-flapping coarse tremor of UE's, ataxia, and a rapidly progressive confusional state developing has months. Measure ___ to diagnose ___

Answer 42

measure ceruloplasmin leve; dx Wilson's disease (autosomal recessive)

Question 43

Neurofibromatosis type 1 is caused by mutation in the 60-exon NF1 gene on chromosome ___

Answer 43

17q

Question 44

Neurofibromatosis type 2 is caused by mutation in the NF2 gene on chromosome ___

Answer 44

22.q12.2

Question 45

Patients with ___ p/w cafe au lait spots, axillary/inguinal freckling, optic glioma

Answer 45

Neurofibromatosis type 1

Question 46

Patients with ___ p/w bilateral acoustic schwannomas

Answer 46

Neurofibromatosis type 2

Question 47

Metachromatic leukodystrophy mode of inheritance is ___; results in a deficiency in ___. Presents with gait d/o with hypotonia and lower limb areflexia.

Answer 47

autosomal recessive; deficiency of arylsulfatase A --> high sulfatide levels --> demyelination

Question 48

"Tay-Sachs disease mode of inheritance is ___ that results in deficiency of ___. Classic infantile picture of developmental retardation, paralysis, dementia, and blindness, with death in 2nd or 3rd year of life. Classic ""cherry red spot"" on fundoscopy"

Answer 48

autosomal recessive; hexosaminidase A deficiency

Question 49

Krabbe's disase mode of inheritance is ___; caused by deficiency in ___; infants p/w rapid deterioration in motor and intellectual development, hypertonicity, optic atrophy, seizures

Answer 49

autosomal recessive; galactocerebrosidase B-galactosidase

Question 50

___ is an X-linked recessive hereditary disorder of purine and pyrimidine metabolism

Answer 50

Lesch-Nyhan Syndrome

Question 51

13 y/o presents with choreoathetosis, hyperreflexia, hypertonia, dysarthria, behavioral disturbances, cognitive impairment, and self-mutilatory behavior. Dx __

Answer 51

Lesch-Nyhan Syndrome

Question 52

In ___, there is an accumulation of excessive sulfatides in the nervous system, which leads to progressive demyelination. Localizes to chromosome 22q13.

Answer 52

Metachromatic leukodystrophy

Question 53

Child presents facial cutaneous angioma (port-wine nevus) on face. Other s/sx include contralateral hemiparesis, mental retardation, homonymous hemianopia. Seizures in over 70%. Dx = ___

Answer 53

Sturge-Weber Syndrome

Question 54

___ has autosomal dominant pattern. P/w retinal and CNS hemangioblastomas and visceral cysts and tumors; renal cysts in about 50% cases; pheochromocytoma in about 10-20%

Answer 54

Von Hippel-Lindau Syndrome

Question 55

"38 y/o F on day 3 following delivery, p/w acute onset ""worst headache of her life"" with bitemporal hemianopsia, neck stiffness, positive Kernig's sign, persistent hypotension. Dx ___"

Answer 55

Sheehan Syndrome Sheehan's syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive hemorrhage during or after delivery. inability to produce breast milk, irregular or absent periods, hot flashes, and a decreased sex drive. Other symptoms may include fatigue, headaches, low blood pressure, and hair loss.

Question 56

___ is autosomal recessive disease that localizes to chromosome 9q13-q21.1. It is the result of unstable expansion of trinucleotide repeat (GAA). P/w gait ataxia, loss of lower extremity proprioception, absence of deep tendon reflexes that begins in adolescence . Death 2/2 hypertrophic cardiomyopathy in about 50% cases

Answer 56

Friedreich's ataxia

Question 57

___ is autosomal dominent with trinucleotide repeat expansion of CTG that codes to chromosome 19q13.3. P/w ptosis, bifacial weakness, frontal baldness, and triangular drooping facies

Answer 57

Myotonic dystrophy 1

Question 58

___ is X-linked recessive d/o. Hyperuricemia results from deficit in hypoxanthine-guanine phosphoribosyltransferase

Answer 58

Lesch-Nyhan Syndrome

Question 59

___ is caused by deletion at short arm of chromosome 5p15.2. P/w severe MR, microcephaly, round face, hypertelorism, micrognathia, hypotonia, low set ears. Newborns p/w cat-like high-pitched cry

Answer 59

Cri-du-chat syndrome

Question 60

Patient with ___ p/w infantile spasms, hypsarrhythmia, and psychomotor developmental arrest

Answer 60

West's Syndrome

Question 61

"Autosomal recessive d/o that p/w microcephaly, ""mousy"" odor, infantile spasms, and light hair/skin pigmentation"

Answer 61

Phenylketonuria

Question 62

___ is the most common congenital viral infection in newborns and is the result of either a primary maternal infection or a viral reactiation in the mother

Answer 62

CMV

Question 63

Klinefelter's syndrome results from ___, p/w small dysfunctional testes, MR, pear-shaped stature

Answer 63

extra X chromosome (XXY)

Question 64

Turner syndrome results from ___, p/w short stature, lack of pubertal sexual development, webbed neck, and heart + kidney abnormalities

Answer 64

absence of X chromosome (XO)

Question 65

Prader Willi syndrome results from ___

Answer 65

deletion on paternal chromosome 15

Question 66

___ is marked by periods of hypersomnia w/ periods of normal sleep in between. During the periods of excessive sleep the patient make wake up and experience apathy, irritability, confusion, voracious eating, loss of sexual inhibitions, disorientation

Answer 66

Klein Levin Sydrome

Question 67

___ is inborn error of amino acid metabolism. Patients may p/w marfanoid habitus, malar flush, glaucoma, mental retardation, seizure, spasticity, psych problems

Answer 67

Homocystinuria

Question 68

"Child p/w delayed mental and social skills, below normal head size, jerking movements, mental retardation, seizures, ""mousy odor"" 2/2 enzyme deficiency"

Answer 68

Phenylketonuria

Question 69

Autosomal recessive d/o that p/w blindness, deafness, and inability to swallow. Patient develops atrophy and paralysis. 2/2 hexosaminidase-A deficiency

Answer 69

Tay-Sachs Disease

Question 70

Most common cause of inherited infantile mental retardation

Answer 70

Fragile X Syndrome

Question 71

"___ is result of autosomal microdeletion on chromosome 7q11. Pt p/w cardiac valvular stenosis, hypotonia, ""elfin"" facies, unusual friendliness with strangers, strong association with ADHD"

Answer 71

Williams Syndrome

Question 72

___ is autosomal dominant connective tissue d/o of fibrillin

Answer 72

Marfan Syndrome

Question 73

___ is caused by deletion of chromosome 15q11-13. P/w developmental delay, aggressive behavior, temper tantrums, overeating

Answer 73

Prader-Willi Syndrome

Question 74

If individual inherits deletion from maternal chromosome 15, the result is ___; if mutation is on a paternal chromosome 15, the result is ___

Answer 74

maternal-Angelman's; paternal-Prader Willi Syndrome