Crouzon syndrome
- Autosomal dominate; high penetrance. Many causes are due to sporadic mutation; increased risk w/ higher paternal age
- Premature craniosynostosis, may be present at birth
- Coronal fused first in most cases===changes in head and facial form
- Midfacial and maxillary hypoplasia
- Orbital propotosis—protrusion of orbital contents
- Brachycephaly-flat head
- Clinically normal hands
- Measurance alteration in proportions of bones of the hand—shorted proximal phalanx of the first and second fingers. Terminal phalanx of the first finger—short thumbs
Cleidocranial dysplasia
- Autosomal dominat-> CBFA 1 gene a transcription factor
- Multiple unerupted teeth, delayed dental eruption, supernumerary teeth, cementum deficient on roots
- Characteristic facial phenotype: frontal bossing, hypertelorism, delayed closure of fontanels
- Hypoplastic/absent clavicles
**Most common autosomal recessive disorder
Cystic fibrosis 1/22 are carries
v. Amelogenesis Imperfecta
- four genes characterize mutations. Can have different inheritance pattern depending on which is altered.
- Most cases cased by mutation in ENAM and inherited n an autosomal dominant patter
- Autosomal recessive pattern: form of the disorder can result from mutation in ENAM or MMP20
- About 5% of amelogeneis caused by x-linked patter…AMELX
- Shows that specific disorder have multiple pattern evidence
Hemophilia A
X linked recessive disease
- Factor VIII deficiency. Bleeding with minimal trauma , fails to clot
- Bleeding into joins – painful and debilitating
- Require factor replacement prior to dental procedure associated with bleeding
X-linked Dominant
i. Males transmits disease to all of daughters but none of his sons…much less common that other patterns of inheritance
ii. Linked to hypoplastic amelogensis imperfect
iii. More severe form in males, females milder
iv. All daughters of affected man will be affected.
v. Affected females offspring each have 50-50 change of being affected
vi. Hypophosphatemia
hypophosphatemia
- Is a X linked dominant disease
- Recurrent spontaneous dental abscess formation affecting multiple non-carious primary teeth…May also affect perm dentition
- High pulp horns large pulp chambers, dentinal clefts, taurodontism
- Skeletal anomalies…bowing of legs
- Elevated serum alkaline phosphatase, low serum phosphate
- Caused by defective resorption of phosphate in proximal renal tubules and inadequate synthesis of Vit D
Hairy pinna
Y- linked disease( only) transmitted father to sons
since Y never effects daughters
Prader-willis Syndrome
paternal mutation effects both sons and daughter
i. Most common form of obesity caused by genetic syndrome
ii. Affects both sexes and any ethnicity.
iii. Infancy: failure to survive, difficultly eating, hypotonia, poor sucking reflux, diminished or absent cry
iv. Developmental delay….after one year hyperphagia
v. Difficult behavior, short stature, hypogonadism, delayed or incomplete puberty
vi. Learning disabilities and may have mental retardation
Angelman Syndrome
A maternal mutation
i. Consistent (100%): *Developmental Delay, *Speech Impairment, none or minimal use of words, movement or balance disorder
ii. Frequent (>80%): delayed, disproportionate growth in head circumference, usually resulting in *MICROCEPHALy, seizeures, onset by <3
iii. Associated (20-80%): hypopigmented skin/eyes, tongue thrusting, sucking disorder, prominent mandible, increased sensitivity to heat, wide mouth, wide spaced teeth, frequent drooling, protruding tongue, excessive chewing /mouthing behaviors, flat back of head
III. Caudal Regression Syndrome
- ALL IMPORTANT
a. Synonyms: Caudal dysplasia, sacral agenesis, sacral regression
b. CRS strongly ass. With maternal diabetes
c. Defects in the primitive streak in the late gastrula
d. Ingression of mesnchymal cells
CAUDAL regression in gastrulation
- Bc Gastrualation begins in caudal area
i. Congenital anomlaies
ii. Pelvic deformity
iii. Complete or partial agenesis of the sacrum
iv. Femoral hypoplasia ( underdevelopment)
v. Lack of motor function below the level of remaining spin AND sensation tends to be present
chordamesoderm
will form notochord. Rod underneath the neural plate that gives support but also signaling center that directs neuralation
What are the inheritance chromosome abnormalities
Numerical: By number of #
Structural: movement or change in dna/protien
iii. Formation of ring chromosomes
Structural , inheratance chromosome abnormality
lead to epilepsy, mental retardation, dwarfism, microcephaly, turner syndrome (if X-chromo),
1. Symptoms seen in pts carrying ring are more likely to be caused by deletion of gene NOT the formation of ring itself
i. Invagination
sheet of cells (epithelial sheet) bends inward
involution
: epithelial sheet rolls inward to form an underlying layer
Ingression
individual cells leave epithelial sheet and become freely migrating mesenchyme cells
List the classifications of Spina Bifida
a. Spina bifidia occulta ( hidden)
i. One of the mildest forms at times asymptomatic
b. Spina bifida cystica:
cyst protudes through vertebral arch
.c. Menignocele
i. Least common form- CNS undamaged- live long lfe
.d. MYELOmeningocele
i. MOST serious and common form
IX. Arnold Chiari Malformation
Cerebellum deformation associated with spina bifida
Cause: genetic pre-disposition ;also brain or head trauma
What is the most common type of Arnold Chiari Malformation
TYPE-1: Abnormal protrusion of tonsils of cerebellum thru foramen magnum down into cerival spinal canal
Type 0 Arnold Chiari Malformation
i. Obstruction caused by small and malformed posterior fossa (small space in skull, found near the brain stem and cerebellum) w/o evidence of cerebral tonsil herniation
g. Symptoms: headaches, neck pain, balance tolerance, muscle weakness, numbness or other abnormal feeling sin arms or legs, ringing or buzzing in ears
i. When hear these complaints may think TMJ…but taking a good medical history is good b/c TMJ problem shouldn’t also have numbness in fingers and legs
what factors affect neural crest cell migration
i. Permissive factors: Fibronectin and Laminin
ii. Inhibitory factors: Ephrins
iii. Negative chemotaxis: Semaphorins
iv. Positive chemotaxis: Neurogulins
j. differentiation is based on what cells they come in contact with at the target
XII. Waardenburg syndrome
recognize it’s a neural crest abnormality
a. Cleft lip(rare)
b. Extremely pale blue eyes or eye colors that don’t match
c. White patch of hair or early graying of hair
d. Deafness
