Genetic Syndromes Flashcards
X-linked recessive muscular dystrophy –> slowly progressing muscular weakness in the legs and pelvis, later in life (pre-teens), no cognitive impairments of myopathy
Becker muscular dystrophy
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
Duchenne muscular dystrophy
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
Friedreich’s ataxia
Multi-systemic disease that affects mainly adults, and results in wasting of the muscles, cataracts, heart conduction defects, endocrine changes, and myotonia
Myotonic dystrophy
X-linked recessive (ABCD1 gene); abnormal protein in peroxisome, responsible for breaking down long chain fatty acids
Adrenoleukodystrophy
X-linked recessive; affects males –> spastic paresis, neuropathy, dementia; adrenal insufficiency common (low sodium, high potassium, low cortisol)
Adrenoleukodystrophy
___ 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.
Metachromatic leukodystrophy
___ is a lysosomal storage disease; autosomal recessive –> neurological deficits including seizures, swallowing difficulties and developmental delays
Krabbe disease
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
Phenylketonuria
Neurological manifestations include chorea, dementia, ataxia, axonal neuropathy and seizures. CK levels and sometimes hepatic transaminases may be increased
Neuroacanthocytosis
Clinical triad of ___ is intellectual disability, seizures, and hamartomas
Tuberous sclerosis
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
Anti- glutamic acid decarboxylase (GAD) antibodies
“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.”””
Rett syndrome
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
Tuberous sclerosis
___ is a genetic disorder where the child tends to also have poor language skills; the child is very friendly and often trusts strangers.
Williams syndrome
___ 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.
Aicardi syndrome
___ is an X-Linked lysosomal storage disease that causes cardiomyopathy, skin lesions and renal failure; deficiency in ___
Fabry’s disease; a-galactosidase A
___ 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.
Rett syndrome
___ is an X-linked recessive condition that is caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase
Lesch Nyhan syndrome
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 ___
low serum ceruloplasmin, low serum copper and high urine copper levels
___ 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
Kleine-Levin syndrome
Creutzfeldt-Jakob disease classically shows ___ on EEG and is positive for ___ in the CSF fluid
periodic sharp wave complexes; specific protein 14-3-3
___ 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)
Rett syndrome
___ 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
Tuberous sclerosis
___ is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin, respectively
Tuberous sclerosis
___ is a severe childhood-onset epilepsy. It is characterized by multiple and concurrent seizure types, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG)
Lennox- Gastaut
___ is characterized by developmental disability and intellectual disability, maternal gene deleted and, paternal turned off by genetic imprinting
Angelman Syndrome Chrom 15
___ 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
Acid maltase deficiency
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?
Rett Syndrome
___ may involve episodic hyperphagia, hypersomnia and hypersexuality
Klein-Levin syndrome
___ 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)
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.
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 ___
dystonia and seizures; an autosomal dominant trait from either parent, but more often paternal
___ 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.
Acromegaly
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.
Edwards syndrome - Trisomy 18
___ 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
Tuberous sclerosis
___ 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
Rett’s Disorder
___ 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
Turner’s Syndrome
___ 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
Klinefelter’s Syndrome
___ results from expansion of trinucleotide repeat sequences at chromosome 4p16.3
Huntington’s Disease
Short palpebral fissures are found in children with ___
Fetal Alcohol Syndrome
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
Fragile X Syndrome
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 ___
measure ceruloplasmin leve; dx Wilson’s disease (autosomal recessive)
Neurofibromatosis type 1 is caused by mutation in the 60-exon NF1 gene on chromosome ___
17q
Neurofibromatosis type 2 is caused by mutation in the NF2 gene on chromosome ___
22.q12.2
Patients with ___ p/w cafe au lait spots, axillary/inguinal freckling, optic glioma
Neurofibromatosis type 1
Patients with ___ p/w bilateral acoustic schwannomas
Neurofibromatosis type 2
Metachromatic leukodystrophy mode of inheritance is ___; results in a deficiency in ___. Presents with gait d/o with hypotonia and lower limb areflexia.
autosomal recessive; deficiency of arylsulfatase A –> high sulfatide levels –> demyelination
“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”
autosomal recessive; hexosaminidase A deficiency
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
autosomal recessive; galactocerebrosidase B-galactosidase
___ is an X-linked recessive hereditary disorder of purine and pyrimidine metabolism
Lesch-Nyhan Syndrome
13 y/o presents with choreoathetosis, hyperreflexia, hypertonia, dysarthria, behavioral disturbances, cognitive impairment, and self-mutilatory behavior. Dx __
Lesch-Nyhan Syndrome
In ___, there is an accumulation of excessive sulfatides in the nervous system, which leads to progressive demyelination. Localizes to chromosome 22q13.
Metachromatic leukodystrophy
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 = ___
Sturge-Weber Syndrome
___ 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%
Von Hippel-Lindau Syndrome
“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 ___”
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.
___ 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
Friedreich’s ataxia
___ 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
Myotonic dystrophy 1
___ is X-linked recessive d/o. Hyperuricemia results from deficit in hypoxanthine-guanine phosphoribosyltransferase
Lesch-Nyhan Syndrome
___ 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
Cri-du-chat syndrome
Patient with ___ p/w infantile spasms, hypsarrhythmia, and psychomotor developmental arrest
West’s Syndrome
“Autosomal recessive d/o that p/w microcephaly, ““mousy”” odor, infantile spasms, and light hair/skin pigmentation”
Phenylketonuria
___ 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
CMV
Klinefelter’s syndrome results from ___, p/w small dysfunctional testes, MR, pear-shaped stature
extra X chromosome (XXY)
Turner syndrome results from ___, p/w short stature, lack of pubertal sexual development, webbed neck, and heart + kidney abnormalities
absence of X chromosome (XO)
Prader Willi syndrome results from ___
deletion on paternal chromosome 15
___ 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
Klein Levin Sydrome
___ is inborn error of amino acid metabolism. Patients may p/w marfanoid habitus, malar flush, glaucoma, mental retardation, seizure, spasticity, psych problems
Homocystinuria
“Child p/w delayed mental and social skills, below normal head size, jerking movements, mental retardation, seizures, ““mousy odor”” 2/2 enzyme deficiency”
Phenylketonuria
Autosomal recessive d/o that p/w blindness, deafness, and inability to swallow. Patient develops atrophy and paralysis. 2/2 hexosaminidase-A deficiency
Tay-Sachs Disease
Most common cause of inherited infantile mental retardation
Fragile X Syndrome
“___ 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”
Williams Syndrome
___ is autosomal dominant connective tissue d/o of fibrillin
Marfan Syndrome
___ is caused by deletion of chromosome 15q11-13. P/w developmental delay, aggressive behavior, temper tantrums, overeating
Prader-Willi Syndrome
If individual inherits deletion from maternal chromosome 15, the result is ___; if mutation is on a paternal chromosome 15, the result is ___
maternal-Angelman’s; paternal-Prader Willi Syndrome
