Craniofacial exam 1 Flashcards
proteins can be turned on and off
aka?
on- phosphorylated
off- dephosphorylated
proteins
complex, 3D molecules
essential for normal human structure and function.
composed of chains of amino acid.
partially or completely folded to determine shape.
(20 amino acids and each protein had unique amino acid chain and unique shape)
humans produce ~30k proteins
the blueprint for making a human?
DNA
DNA - coiled ladder shape
- rungs..
composed of nucleotides
two nucleotides pair to form each rung.
Types of nucleotides
- adenine
- guanine
- thymine
- cytosine
which nucleotides pair together?
cytosine-guanine
adenine-thymine
where is most of our DNA found?
in the nuclei of all our cells
- but also found in mitochondria
components of a gene
- promoter (starting point for gene’s activity)
- coding region - exon (codes for specific amino acid. sequence of 3 nucleotides)
- Introns (non-coding DNA between exons
98% of DNA is what?
- Non-coding DNA
How many human genes?
20k to 25k
Non-coding DNA
- intons (sections within genes)
- also sequences between genes
- function isn’t completely understood
- some play role in gene expression
What are variations of a gene?
alleles
RNA
- copies the protein recipe from the gene.
- RNA -> single strand of nucleotide
- Uracil replaces thymine
RNA protein copying process
- DNA unwound
- 2 pairs separate
- one side as template
- enzyme matches new nucleotides to appropriate partner on DNA (This is called transcription)
- splices out interon.
- binds nucleotides into a strand (mRNA)
- mRNA exits nucleus and travels to ribosome
- ribosome makes the protein.
What is transcription?
- This is started in the nucleus
- making of mRNA
What is translation?
This is the baking.
- the making of the protein
- in the ribosome
Making of the protein
- made by the ribosome
- tRNA supplies amino acid to the ribosome
- ribosome assembles them according to recipe
- this is called translation ***
what are chromosomes?
strands of DNA and associated proteins.
- compact way to protect, organize and package DNA into the cell.
- 46 total chromosomes in each cell.
- 23 pairs (22 autosomes and 1 sex chromosome)
- x-shaped
Chromosome shape
x shaped central narrowing -> centromere p - short arms q - long arms Bands along the arms. These bands are numbered
Gene location specified by…
chromosome number, arm, and band number or range
ex. FOXP2 gene - 7q31
Mitochondrial DNA
located in each cell’s mitochondria
contains 37 genes
genes code for enzymes essential for mitochondrial function
Gene mutations
- affect a single gene
- changes nucleotide sequence
- occur in two ways
- results in incorrect or non-functional protein.
two ways gene mutations occur
hereditary - present throughout lifetime and in every cell.
acquired - caused by environmental factors or error in DNA copying during cell division
Types of mutations
- substitutions - one nucleotide replaced by another.
- insertion of nucleotide
- deletion of nucleotide
Patterns of inheritance of mutations
- autosomal dominant - only one gene mutation on an autosome.
- autosomal recessive - requires 2 mutations (one on each autosome).
- x-linked - mutation on X chromosome. Typically affects males more than females.
categorization of anomalies
- syndromes
- sequences
- associations
mutations are…
when something goes wrong with genes or chromosomes
Syndromes
- multiple anomalies having a single cause.
2. may be chromosomal or gene-based.
Chromosomal syndromes may result from…
- deletion of whole chromosome.
- addition of whole chromosome.
- addition of part of chromosome.
- restructured chromosome.
- rearrangement of chromosomes.
syndromes caused by chromosomes
- problems present
typically present with severe problems that may include:
- intellectual disability.
- short stature
- heart anomalies
- brain anomalies
- limb anomalies
as well as most have craniofacial malformations and communication problems.
whole chromosome deletion
Rare
example: Turner Syndrome
Turner Syndrome
- affects females only
- all or part of one X chromosome missing
- problems may include:
- short stature
- webbed short neck with low posterior hair line.
- infertility
- variable cognitive and cardiac anomalies
- variable physical anomalies.
Whole Chromosome Addition
- additional chromosome results in a trisomy
- rare with exception of Down Sydrome
- problems may include: 1. cognitive impairment, 2. midface deficiencies, 3. cardiac anomalies, 4. upslanting eyes
Chromosome deletions
- most common chromosomal abnormality.
- example: cri du chat
Cri Du Chat
caused by deletion of short arm of chromosome 5
- problems may include: 1. cognitive impairments, 2. cardiac problems, 3. facial asymmetry, 4. hypertelorism
most congenital anomalies are ..?
genetic-based disorders caused by single gene disorder
Gene disorders can often be predicted by ..?
mode of inheritence:
- autosomal dominant
- autosomal recessive
- X-linked recessive
- X-linked dominant
Sequences
- multiple anomalies triggered by a single structural anomaly or error in development.
some common sequences
- Robin sequence
2. DiGeorge sequence
Robin sequence
- developing child presents with micrognathia
- > micrognathia leads to abnormal placement of tongue.
- > displaced tongue leads to cleft palate.
Associations
- multiple anomalies that occur together more often than would be predicted by chance.
- limited number of associations have been identified.
- examples: VACTERL and CHARGE
Teratogens
- can cause morphological and/or functional anomalies when the fetus is exposed to them.
Teratogenicity
depends on the ability of the teratogen to cross the placenta.
- effects depend on: potency of the teratogen, duration of exposure, and when the fetus is exposed.
examples of teratogens
- therapeutic drugs
- alcohol
- infectious agents
- radiation
Genetic testing
- examination of genes
- examination of chromosomes
- biochemical testing (proteins and enzymes)
Newborn Genetic screenings
- required in all states
- number of screened disorders varies by state
- MI screens for 50+ disorders
Karyotyping
- used to examine chromosomes (number and structure)
- almost any tissue can be used
- takes about a week to get results
- type of genetic testing
Fluorescence in situ hybridization (FISH)
- maps genetic material in a person’s cells
- used to visualize specific genes or portions of genes.
- results available much faster than karyotyping
genetic counseling
- after testing, family is seen for genetic counseling.
- results are presented
- questions are answered
- planning for medical interventions, if necessary
- determine risk of recurrance
SLP role in syndrome ID
- understanding the effects on communication and other developmental issues.
- interaction with other professionals for patient management.
- making referrals for further study.
Normal development of the palate
- primary palate begins at 7 weeks
- secondary palate begins at 9 weeks
- develop independent of one another.
- closure begins at the incisive foramen and proceeds forward to form the alveolar ridge and then lip. Then backward to form the hard palate and velum.
Primary palate
- wedge-shaped
- consists of 1. median portion of the upper lip, 2. alveolus, 3. anterior portion of maxilla to the incisive foramen
- incisive foramen
- Alveolus and anterior part of maxilla also known as the premaxilla
Secondary Palate
- Palatal shelves or palatine processes that fuse to form the hard palate and soft palate.
cleft lip/palate
- lack of fusion of the lip, alveolus, hard palate, and/or soft palate.
- each child is different and presents with different degree of cleft.
- many children with clefts also present with other associated anomalies.
- vary in severity.
when does cleft lip/palate occur
- during the early embryonic period and is present at birth.
classification of clefts
- primary palate (cleft lip)
a. complete, b. incomplete, c. unilateral or bilateral - secondary palate (cleft palate)
a. complete, b. incomplete
submucous cleft
- oral mucosa is intact
- underlying muscle and/or bone is clefted
Cleft lip/palate statistics
- frequency between 1:500 and 1:750 births
- complete clefts of the lip and palate are more frequent than isolated clefts of the lip or palate.
- more males show clefts of the lip and palate than females.
- more females exhibit clefts of the palate only.
- high rate in Asians than Caucasians and higher in caucasians than african americans
- associated anomalies more likely to occur in cleft palate only.
- associated anomalies more likely to occur in bilateral cleft lip and palate than unilateral clefts.
theories of isolated cleft lip/palate
- two major theories:
1. multifactorial threshold model
2. major gene hypothesis model
multifactorial model
- theory for isolated cleft lip/palate
- posits a threshold for expression of a cleft
- combination of genetic and environmental factors must exceed a threshold for a child to be born with a cleft
- used frequently in genetic counseling for isolated clefts.
major gene hypothesis
- theory for isolated cleft lip/palate
- isolated clefting is caused by some single mutant gene
multiple anomalies and clefting statistics
- more than 350 different syndromes include clefting as one of the presenting conditions.
- ~60% of patients present with isolated cleft lip with or w/o cleft palate.
- ~40% of the population have a syndrome.
craniofacial anomalies
- at birth, cranial bones are bonded together by loose connections called sutures.
- sutures allow skull to grow as the child’s brain grows.
- sutures eventually close and become solidified
- if a suture(s) close too early skull growth is restricted (craniosynostosis)
- occurs at rate of ~1:2000-3000 births
4 types of synostosis
- sagittal synostosis- most common- skull becomes long and narrow.
- coronal synostosis- 2nd most common
- metopic synostosis- pointed or triangular forehead from top- sides of forehead appear pinched causing eyes to look like they are too close together.
- Lamboid synostosis- one of most infrequent- flattening of the head on the affected side.
Identify Anomalies
- ~70% of congenital anomalies are present in the head, face, and limbs.
- observations of these areas noninvasive and can be easily carried out by an SLP.
- SLP makes referral to a geneticist for confirmation and/or further testing.