Mhg Lecture 20 - An Introduction To Clinical Genetics

Front 1

How many autosomes do we have? Sex chromosomes? How many copies of each do we have?
How many chromosomes in total?

Back 1

There are 22 autosomal chromosomes.
-->These are chromosomes that are not involved in determining a human's sex.
-->Each person has 2 copies of each autosomal chromosome; one set is inherited from each parent.

The sex chromosomes are called X and Y and determine a human's sex.
-->Females have two X chromosomes.
-->Males have an X and a Y chromosome. 

So human individuals have 46 chromosomes in all
-->2 sets of 22 autosomal chromosomes and either XX (female) or XY (male) chromosomes.

Front 2

What are the two arms of the chromosome called?

Back 2

There are two "arms" to each chromosome

They are called p and q, which are defined by a central pinched section called the centromere.

P = “petite” --> always the smaller arm

Q is named after that because it’s the letter that follows P



(The black and white banding pattern is due to a particular staining technique used to visualize the chromosomes.)

Front 3

How many genes in the human genome? How many on each chromosome?

Back 3

In the human genome there are 20,000-25,000 genes total.

There are 100’s to 1000’s on each chromosome

Front 4

What fraction of infant mortality rates can be related to birth defects and genetic eitologies?

Back 4

-Medical genetics is a central component of understanding rare and common conditions.

-Currently 1/3 of all infant mortality rates can be related to birth defects and genetic etiologies

Front 5

What percentage of all newborn populations are born with some type of birth defect?

Back 5

-About 2-3% of all newborn populations are born with some type of birth defect.

-Long term, these birth defects and genetic disorders are major contributors to developmental disabilities.

Front 6

What accounts for 50% of pediatric hospital admissions?

Back 6

-Genetic disorders and congenital anomalies account for 50% of pediatric hospital admissions

-Because all component of the human body are influenced by genes, genetic disease is relevant to all medical specialists.

Front 7

What is Noonan Syndrome

Back 7

Genetic disorder that results in things like:

A. low set ears
-->Note that his ears are low set
B. downslanting eyes / downslanting palpebral fissures
C. broad neck
D. Pointed chins
E. broad foreheads
F. congenital heart anomalies
G. Eye anomalies
H. Short stature
Inherited in an autosomal dominant manner
Both mom and son in this picture on the bottom right are affected

Front 8

What proportion of genetic disorders are due to single gene disorders?

Back 8

Single Gene Disorders:

~ 1/500 of genetic disorders are due to single gene disorders

Single gene conditions, also called Mendelian conditions, are caused by an error in a single gene, a single unit of genetic information. They exhibit characteristic patterns of inheritance in families. It is estimated that single gene disorders occur in 1 in 500 individuals in the general population. In several hundred of these conditions, the affected gene has now been identified. Although the majority of single gene conditions are rare, their combined effect is significant. Examples include sickle cell disease, fragile X syndrome, achondroplasia, and certain forms of hereditary breast and colon cancer.

Front 9

Chromosomal disorders account for:
a. what percentage of live births?
b. what percentage of children with severe mental retardation and multiple congenital anomalies?
c. what percentage of spontaneous abortions that occur in the first few weeks in pregnancy?

Back 9

Chromosome Disorders account for:
a. 0.7% of live births

b. 10-15% of children with severe Mental Retardation (MR) & Multiple Congenital Anomalies (MCA)

c. 50% of spontaneous abortions that occur in the first few weeks in pregnancy are thought to be related to chromosome disorders


Chromosome conditions are caused by an excess or deficiency of a chromosome segment or an entire chromosome, and in general are not inherited. An affected person may have mental and physical retardation, unique physical features, and congenital anomalies. People with sex chromosome conditions may display mild developmental and behavioral problems, tall or short stature, and infertility. An example of a chromosome disorder is Down syndrome, a condition in which an individual has an extra Chromosome 21. Chromosome disorders occur in 0.7% of live births, in 10-15% of children with severe mental retardation and congenital malformations, and in 50% of spontaneous abortions that occur in the first few weeks in pregnancy. Chromosome abnormalities can also be seen in certain types of cancer cells.

Front 10

What are multifactorial disorders?
What percentage of the population do they affect?

Back 10

Multifactorial Disorders:

-very common

-Include things like hypertension or Alzheimer's

-Affect 10-40% of the entire population


Multifactorial conditions result from the combination of genetic predisposition and environmental factors. In general they do not show a specific inheritance pattern. However, they tend to occur more often in families than would be expected by chance. They are common conditions, and account for many chronic conditions of children and adults. Examples include mental illnesses, asthma, some heart diseases, certain cancers, and diabetes. Multifactorial conditions may also be involved in birth defects such as cleft lip and/or palate, clubfoot, and many congenital heart defects.

Front 11

Are mitochondrial disorders common or rare?

Back 11

Mitochondrial Disorders are rare !

Mitochondrial conditions became known only a few years ago and are relatively rare. It was previously thought that all DNA was contained in the cell nucleus. It is now knows that some DNA is located in the area just outside the nucleus called the mitochondria. Mitochondrial disorders are transmitted by the mother and may affect either male or female children.

Front 12

What are single gene disorders also called?

What are they caused by?

Back 12

-Also called Mendelian conditions

-Caused by an error in a single gene, a single unit of genetic information

-They exhibit characteristic patterns of inheritance in families

-They exhibit specific phenotypes or patterns of abnormalities that we can look at and identify

-In several thousands of these conditions, the affected gene has been identified
-->We are still early in the genetics phase
-->We don’t know why all the genetic disorders occur

-The majority of single gene conditions are rare, but their combined effect is significant to the medical world


What are some examples of single gene disorders?

Hint 12

Examples:
a. sickle cell disease
b. fragile X syndrome
c. achondroplasia
d. certain forms of hereditary breast and colon cancer

Front 13

What are chromosome disorders caused by?

Are they inherited?

What are the symptoms?

Back 13

-Caused by an excess or deficiency of a chromosome segment or an entire chromosome.

-In general not inherited

-Symptoms:
1. mental & physical retardation
2. Unique physical features
3. Congenital anomalies

-Disorders of sex chromosome:
1. Mild developmental and behavioral problems
2. Tall or short stature
3. Infertility


What are some examples of chromosome abnormalities?

Hint 13

Examples:
Down syndrome, 47, + 21

Chromosome abnormalities can also be seen in certain types of cancer cells.
-->This is different than what we’re talking about when we’re talking about chromosome disorders in a person that they were BORN with

Front 14

What is Fragile X?

What gene is mutated?

What are the main features you see in individuals with Fragile X?

Back 14

-Another genetic disorder that is caused by mutations of a gene called FMR1 on the X chromosome

-This type of disorder presents mainly in males

-You see in childhood the main features really are larger ears, perhaps slightly low set, prominence of the forehead, the head shape may be a little bit odd.

-As these children grow up to be adults then the features really come out and stand out as tall, elongated facies, pointed chins, large ears, mental retardation, can have macroorchidism (Macroorchidism is a genetic disorder found in males where a subject has abnormally large testes.)

-Females who may be affected usually have much milder phenotypes

Front 15

Gene

Back 15

-a sequence of DNA required for production of a functional protein

*A gene must have a functional protein

Front 16

Pseudogenes

Back 16

-Genes that may or may not be transcribed but do not lead to an end function.

*A gene must have a functional protein

Front 17

Locus

Back 17

-physical position of a gene within a chromosome.

-The elastin gene is located at 7q11.23

eg. Gene for Williams syndrome is called ELN
-->That’s the gene because it has a protein that is functional
-->The locus of the ELN gene is located here at 7q11.23
-->This means it’s on chromosome 7 on the q arm because it’s on the long arm and the position is 11.23

Front 18

Allele

Back 18

-one member of a pair of genes that occupies a locus and controls the same trait.

-For every gene, there are two copies (one from mom and one from dad), but small variations or polymorphisms give different alleles

-For the ELN gene that we just talked about, we have two loci --> one on the maternally inherited chromosome 7 and one on the paternally inherited chromosome 7

(keep in mind, at the bottom of the slide she wrote "Add question about sickle cell trait, Hg C vs normal, due to different alleles.")

Front 19

Mutation

Back 19

-any permanent change in the DNA sequence.

-Size can be one single base pair to a large segment of a chromosome



Gene mutations occur in what two ways????

Hint 19

** inherited or acquired **

INHERITED MUTATIONS are called germline mutations because they are present in the egg and sperm cells.
-->This type of mutation is present throughout a person’s life in virtually every cell in the body.

*If a germline mutation is not inherited from a parent but occurs in the fertilized egg, this is called a de novo mutation (new mutation in that individual)


ACQUIRED MUTATIONS are called somatic mutations because they occur some time during a person’s life in cells other than the egg and sperm.
-->caused by environmental factors (UV radiation), viruses, DNA replication mistake etc.
-->Acquired mutations cannot be passed on to the next generation

Front 20

Polymorphism

Back 20

-an allele sequence that occurs in 1% or more of the population

-Usually we refer to a polymorphism as a normal finding but in reality, based on its terminology, it’s just a statistical term that it’s present in more than 1% of the population

-In some cases, polymorphisms which have been reported as normal variants have been found to predispose to multifactorial disease such as hypertension


What is a rare variant?

Hint 20

Rare variant:
an allele sequence that occurs in <1% of the population



*Note: Polymorphism and rare variant are both statistical terms – they don’t represent whether this is a mutation or not

Front 21

What are different types of mutations and their effect on protein function?

Back 21

Type of mutation:

-Point mutation
a. Missense
b. Nonsense

-Insertions, deletions

Effect on protein function
-->Loss of function
-->Gain of function
-->Dominant negative

Front 22

Missense mutation

Back 22

-Point mutation

-cause a misspelling

-Changed A.A.

-conservative – new a.a. is similar in chemical structure

Front 23

Nonsense mutation

Back 23

- stop the protein from being transcribed

First AID says: “STOP the NONSENSE!!!!”

Front 24

What is a loss of function mutation?

Give an example.

Back 24

-A mutation that is associated with a reduction or complete loss of a function of the protein.



Eg. RB1 gene is associated with retinoblastoma

Front 25

What is retinoblastoma? How do patients get it?

Back 25

-It’s a tumor suppressor gene and regulates the cell cycle

-To have retinoblastoma, both copies of the RB1 gene have to be mutated, resulting in loss of function of the gene product (protein)

-In 40% of patients with retinoblastoma, one allele of the RB1 gene is inherited already with a mutation. That individual only needs to sustain an additional mutation in the other allele that they acquire somatically and then they develop retinoblastoma.
-->Since they have one inherited allele, retinoblastoma in this case is usually bilateral (both eyes may be affected), with early onset
-->On the left is the inherited form where there is already a mutation
-->Because there is a mutation that means every cell in the retina already has one mutation of the Rb1 gene
-->It makes sense that it is a little bit easier for a second mutation to occur in any of these cells, and therefor multifocal or bilateral retinoblastoma can occur

-In 60% of patients with retinoblastoma, both alleles of the RB1 gene each acquire a mutation somatically
-->Retinoblastoma in this case is unilateral and later onset in childhood.
-->On the right there is no mutation, so the retinal layer of the eyes is healthy without any mutations and one of these cells has to acquire two mutations in the Rb1 gene for retinoblastoma to occur unilaterally

Front 26

What is a Gain of Function mutation?

Give an example.

Back 26

-A mutation associated with an increase in the normal function of a protein

Eg. Achondroplasia

FGF = fibroblast growth factor
FGFR3 = fibroblast growth factor receptor 3

Front 27

What is achondroplasia characterized by?

Back 27

Achondroplasia is characterized by short stature with disproportionately shorter limbs, a large head, some midface hypoplasia and indentation with frontal bossing, sometimes protrusion of the forehead

Front 28

What is a dominant negative mutation?

What is it usually related to?

Give an example!

Back 28

-a mutation in one allele disrupts or antagonizes the function or product of the other allele

-Usually related to structural proteins

Eg. Type 1 collagen is a major structural protein of bone and fibrous tissue
-->Triple helix of 2 alpha 1 chains and 1 alpha 2 chains
-->A defective product of one can effect the normal scaffolding
-->If the triple helix can’t form you end up with a disorder called osteogenesis imperfecta or OI
-->Have a mutation in one of the alpha I proteins and so the triple helix doesn’t form nicely
-->The strength of the helix or the collagen becomes poor
-->These individuals with osteogenesis imperfecta have multiple fractures, bent bones, they can also have dental anomalies, blue sclera, and hearing loss

Front 29

What is Ehlers Danlos syndrome?

Back 29

-These individuals have a problem with their connective tissue where they have a significant elasticity

-They can bend their fingers in all kinds of angles, they can extend their skin more than most people would

-But because of this they have problems with recurrent hernias and also scarring that forms these atrophic scars
 

(An atrophic scar takes the form of a sunken recess in the skin, which has a pitted appearance.) 

Front 30

What is the difference between clinical or phenotypic heterogeneity and genetic heterogeneity?

Back 30

Clinical or phenotypic heterogeneity
-->Mutations in the same gene cause different phenotype/disease

Genetic heterogeneity: two types
WHAT ARE THEY?!

Hint 30

Allelic heterogeneity:
-->different mutations/alleles cause similar phenotype

Locus heterogeneity:
-->different loci (different genes) cause similar phenotype

Front 31

What is clinical heterogeneity?

Give an example!

Back 31

Different mutations in the same gene lead to different phenotype: RET gene

Specific mutations in the gene in specific areas can also present with Hirschsprung Disease and NOT MEN2B


(see back of card for details on these symptoms!)

Hint 31

Pheochromocytoma is a rare tumor of adrenal gland tissue. It results in the release of too much epinephrine and norepinephrine, hormones that control heart rate, metabolism, and blood pressure .

A mucosal neuroma is a tumor of the facial nerves that appears on the mucous membranes—that is, soft areas of the skin such as those inside the mouth, on and around the lips, and under the eyelids. Although mucosal neuromas themselves are not cancerous, their appearance is often associated with certain kinds of cancer.


Marfanoid (or Marfanoid habitus) is a constellation of symptoms resembling those of Marfan syndrome, including long limbs, arachnodactyly, and hyperlaxity.

Hirschsprung disease (HD) is a motor disorder of the gut, which is caused by the failure of neural crest cells (precursors of enteric ganglion cells) to migrate completely during intestinal development. The resulting aganglionic segment of the colon fails to relax, causing a functional obstruction. In the majority of patients, the disorder affects a short segment of the distal colon, with a transition zone in the rectosigmoid colon. In other patients, the aganglionosis involves longer segments of the colon. In approximately 5 percent the entire colon is affected, and in rare cases the small bowel may also be involved

Front 32

Are environmental causes of birth defects common?

Back 32

Environment causes (teratogenic) of birth defects are infrequent (> 5%)

Front 33

In the US, what represents the most frequent cause of mortality during the first year of life?

Back 33

In the United States, congenital malformations represent the most frequent cause of mortality during the first year of life

Front 34

Genomics

Back 34

The study of functions and interaction of all the genes in the genome. Genomics has a broader and more ambitious reach than genetics

Front 35

Clinical Genetics

Back 35

Deals with the direct clinical care of persons with genetic disorders

Front 36

Medical Genetics

Back 36

The study of the genetics of human diseases

Front 37

Dysmorphology

Back 37

The study of abnormal physical development

Front 38

What is allelic heterogeneity? AND give an example.

Back 38

-different mutations or alleles of the same gene can produce similar phenotypes

-ex: there are many mutations in the CF gene and all of them result in CF

Front 39

What is locus heterogeneity? AND give an example.

Back 39

-mutations in different genes cause same phenotype

-ex: retinitis pigmentosa
-339 different genetic syndromes have RP as a feature, most of these are caused by different genes with different associated findings
-inheritance is also different for these genes, AD, AR, and X-linked RP have been reported

Front 40

What is phenocopy? AND given an example.

Back 40

-an environmentally induced phenotype that mimics the phenotype produced by a specific genotype

ex: 22q11 deletion/DiGeorge syndrome and retinoic acid embryopathy

What are their symptoms?

Hint 40

DiGeorge syndrome
1. Conoctruncal or aortic arch defects
2. Small cupped ears
3. Low normal IQ
4. Velopharyngeal insufficiency/clefting
5. Thymic hypo/aplasia
6. Parathyroid hypo/aplasia

Retinoic acid embryopathy
1. conoctruncal or aortic arch defects
2. small ears
3. low IQ
4. cleft palate

Front 41

What are teratogens?

Back 41

-an agent that crosses the placental barrier and induces structural malformations, growth deficiency, and/or functional alterations during prenatal development

-cause a small percentage of all congenital malformations, however, they are an important category to identify and prevent

What are some categories of teratogens?

Hint 41

1. prescription drugs
2. illicit substances
3. chemical and physical agents
4. maternal metabolic/ genetic factors (maternal diabetes)
5. infectious agents

Front 42

What does the effect of a teratogen depend on? Give 3 examples of teratogens.

Back 42

when it was introduced in the fetal growth cycle

What are some symptoms of FAS, fetal hydantoin syndrome and thalidomide?

Hint 42

FAS
1. smooth filtrum
2. microcephaly
3. mental deficiency

Fetal hydantoin syndrome
1. microcephaly
2. nail abnormalities

Thalidomide
1. problems with limbs

Front 43

What is pleiotropy? AND give an example.

Back 43

-multiple phenotypic effects of a single gene

-ex: stickler syndrome
-everyone will have the collagen 2A1 mutation BUT the phenotypic effects can vary

What are some of its features?

Hint 43

1. myopia/retinal detachment
2. deafness
3. cleft palate
4. midface hypoplasia
5. skeletel dysplasia

Front 44

What is the difference between penetrance and expressivity?

Back 44

1. Penetrance: fraction of individuals with a genotype known to cause disease who have ANY signs/ symptoms of the disease (think of an on/off light switch)

2. Expressivity: the extent to which a genetic defect is expressed. The trait may vary from mild to severe, but NEVER unexpressed in those with the genotype. (think of a dimmer switch)

Front 45

What is an example of penetrance?

Back 45

-family pedigree of BRCA mutation
-8 individuals have the mutation
-5 have disease associated with the mutation
-penetrance: 5/8 = 63%

Front 46

What is an example of expressivity?

Back 46

-family pedigree of achondroplasia
-7 individuals have the mutation
-7 have disease associated with the mutation
-penetrance: 7/7=100%

-each individual with the mutation has a variable presentation = variable expressivity

Front 47

What are the symptoms of bardet biedl?

Back 47

*this is a disease with variable expressivity

-problems with retinitis pigmentosum: night blindness in childhood

-polydactyly

-syndactyly

-truncal obesity

-renal problems

Front 48

What are 4 things associated with somatic development?

Back 48

1. malformation
2. dysplasia
3. deformation
4. disruption

Front 49

What is a malformation?

Back 49

-localized abnormalities in organogenesis

-intrinsic to the embryo or fetus

-MAJOR: interferes with function, requires medical attention, 3% of full term births (ex: cleft lip/ cleft palate)

-MINOR: no serious health problems, 17% of full term births (ex: ear pick? or supernumerary nipple)

Front 50

What is a dysplasia?

Back 50

-an INTRINSIC defect that causes abnormal organization of cells; abnormal tissue development. All the components are present but unorganized appropriately

-ex: ectodermal dysplasia- poor teeth and nail formation in addition to thinning hair

Front 51

What is a deformation?

Back 51

-an EXTRINSIC mechanical force that impairs ongoing normal fetal development. The force can change the shape form and position of the body

-ex: low amniotic fluid will lead to fetal akinesia, joint constrictures, pterygium

Front 52

What is a disruption?

Back 52

-EXTRINSIC force destroys tissue or organ that had already developed normally

-ex: amniotic and sequence - amnion ruptures and gets entangled in the fetus

-as the fetus grows, it can cause limb constriction, missing parts of the fingers or extremities or cleft palates, etc.

Front 53

What are multiple abnormalities of somatic development? AND give an example for each.

Back 53

1. syndrome: a recognizable pattern of anomalies that are due to a single etiology (ex: DS)

2. association: a grouping of congenital anomalies found together more often than expected by chance with no known common etiology (ex: VACTERL association)

3. sequence: a series of congential anomalies derived from a single defect with secondary structural changes (ex: robin sequence)

What are the symptoms for each of those examples?

Hint 53

DS:
1. Hypotonia
2. Flat face
3. Slanted palpebral fissures
4. Abnormal auricles
5. Simian crease
6. Clinodactyly
7. Congenital heart defect
8. LD/DD
9. GI anomalies
10. Eye anomalies
11. Epicanthal folds

VACTERL associatino:
1. Vertebral defects
2. Anal atresia
3. Cardiovascular anomalies
4. Tracheo-esophageal fistula
5. Esophageal atresia
6. Renal or radial anomalies
7. Limb defects
(*we don't know the underlying genetic reason as to why this happens but patients will typically present with a combination of these)

Robin sequence
1. mandibular hypoplasia
THEN
2. Posterior tongue displacement
THEN
3. Cleft palate

Front 54

What is Waardenburg syndrome?

Back 54

-Individuals have a white patch in their hair

-All have profound congenital hearing loss

-defect that leads to pigment abnormalities (white patch of hair, white spots on skin)

-Also have right blue eyes

Front 55

What are the 4 different inheritance patterns?

Back 55

1. AD

2. AR

3. X-linked

4. Mitochondrial

Front 56

Describe AD inheritance.

Back 56

-Affected usually have an affected parent

-Either sex affected

-Transmitted by either sex

-Offspring of an affected has a 50% chance of being affected

-Male to male inheritance present

Front 57

Describe AR inheritance.

Back 57

-Affected usually born to unaffected parents

-Parents of affected are asymptomatic carriers

-Either sex affected

-Increased incidence of consanguinity

-Carrier parents have a 25% chance that each child will have the disorder

Front 58

Describe X-linked inheritance.

Back 58

-Affects mainly males

-No male to male transmission

-Affected males usually born to unaffected parents, mother usually asymptomatic carrier who may have affected male relatives

-Females may be affected with milder symptoms depending on skewed X inactivation

Front 59

Describe mitochondrial inheritance.

Back 59

-Maternal inheritance only

-All offspring of affected mother inherit mutation, none inherit from father

-Expression of mitochondrial disease depends on relative proportion of normal and mutant mitochondrial DNA in cells in different tissue, therefore variable expressivity.

Front 60

What are the reasons for a genetic referral/consulation?

Back 60

Prenatal:
-Couples either preconception or pregnant with a child:
-Family history of a specific disorder or an anomaly that runs in the family
-Abnormal maternal screening or ultrasound during the pregnancy

Pediatric:
-A suspicion that the child has physical external or internal anomalies
-Has growth problems, developmental delays, intellectual disability

Adult:
-A suspicion that an adult may have a genetic disorder either due to behavior, mental deterioration, specific medical problems
-A significant personal or family history of cancer in the family

Front 61

What does making a genetic diagnosis depend on?

Back 61

*The process of diagnosing a genetic disorder is a complex sequence of events

It depends upon:
1. Collection of information
2. Physical examination
-knowledge and skills in the recognition of mild malformations, minor anomalies, and phenotypic variations
3. diagnostic decision making
4. laboratory diagnosis
5. Genetic counseling
6. Referral to support groups and other specialists for further evaluation and treatment of compounding anomalies

Must also take into account: Personal and family history, pedigree, causes of death, age of death, prophylctic surgeries, newborn screen

Front 62

What is the significance of an accurate diagnosis?

Back 62

**In clinical genetics, it is the MOST IMP. step in patient care!!

-The significance of accurate diagnosis can’t be overemphasized

-Genetic counseling begins with an accurate diagnosis

-Discussion of natural history, prognosis, management, risk determination, options for prenatal diagnoses, and referral to advocacy group depends on accurate diagnosis

Front 63

Dr. Saadeh presented a case at the end of the lecture: Here are the deets!!

-19 year old female comes for:

-6 month history of slurred speech, aphasia, abnormal gait with loss of balance, toes camping together and left knee locking

-History of psychotic disorder, depression and OCD all beginning in childhood

-Has a right bone spur of the heel that was injected with steroids that the family seems to feel precipitated these recent events

-Brain MRI in June suggests abnormal signals in the bilateral putamen, midbrain and posterior aspect of the pons

-Multiple previous consultations with neurologists and psychiatrists w/o diagnosis

-College student, average performance

THEN a physical exam was performed:

Back 63

-Slurred speech sometimes difficult to understand

-Took many efforts to get words out

-Over exaggerated swallowing efforts

-Ataxia, difficulty getting out of chair, difficulty walking and when eyes closed, loses balance. Otherwise neurological exam intact

-Skin lesions from OCD, disheveled looking at first visit

Then a Diagnostic workup was made:

Hint 63

Diagnostic workup:
-MRI findings consistent with acquired toxic insults such as hypoglycemic encephalopathy, carbon monoxide poisoning, methanol toxicity, ethylene glycol toxicity and cocaine encephalopathy. No such history in this patient.

-Can also be seen in wilson’s disease: a genetic disorder in which copper accumulates in tissues:

-Neurological (movement disorders such as tremors, poor coordination, loss of fine motor control, choreoathetosis or rigid dystonia with rigidity, gait problems, difficulty swallowing and dysarthria

-Psychiatric symptoms (depression, neurotic behavior, personality disorders and occasionally intellectual deterioration

-Liver disease (jaundice, hepatitis, liver disease or liver failure

-Copper accumulation in the eyes results in kayser-fleischer rings

LAB RESULTS:
-Liver panel normal
-Cerruloplasmin low, urine copper very high
-Ophthamology exam: kayser-fleisher rings
-Genetic testing for the ATP7B gene showed two mutations, confirming the diagnosis of this AR disorder