Lecture 3 Genetics & Syndromes

Craniofacial anomalies tend to reoccur in families. The risk for recurrence is variable depending on interactions of multiple
environments & genetic factors
Prenatal Diagnosis & Prevention
 Prenatal diagnosis for CL w/or without CP depends on the ability of ultrasound to see the baby’s face in the
womb
 An ultra sound is designed to check the baby’s anatomy & is therefore the best method for prenatal diagnosis of
cleft lip w/or without cleft palate
o Ultrasound: is designed to check the baby's anatomy & is therefore the best method for prenatal diagnosis
of cleft lip w/or without cleft palate.
 With current technology & a fetus that happens to be in the perfect position for scanning, the chances for prenatal
diagnosis of cleft lip are reasonably good but the baby’s positioning does not support adequate scanning of the
baby’s face to assess for cleft lip. Attempts will be made to reposition the mother to stimulate movement of the
baby for better imaging or a repeat ultrasound will be scheduled if warranted
 The cleft palate that is seen in the ultrasound is actually the alveolar ridge. Current technology does not routinely
visualize most of the hard palate or the soft palate of the developing baby & therefore the extent of clefting of the
palate can be difficult to determine prenatally.
 There is some evidence that taking folic acid before becoming pregnant may reduce the risk for isolated clefts
 Although folic acid supplementation is not believed to reduce the risk of clefts associated w/syndromes, it is
recommended as a general preventive measure for all women contemplating pregnancy. Recommendation is a
daily vitamin supplement of 400 mg of folic acid for all pregnant women. This dose is provided by most over the
counter multivitamins.
Common Questions:
1. Why this happened to the child?
2. What the chances are that other children w/clefts will be born into the family?
As their children reach adolescence, parents may wonder what to tell the child who has a cleft, as well as other children
in the family, about their own risks of having a baby w/a cleft. These questions are most accurately answered by a
clinical geneticist.
Genetics
 The exact cause of clefting is unknown in most cases. For most cleft conditions, no single factor can be identified
as the cause however it is important to distinguish between isolated clefts in which the patient has no other related
health problems & clefts associated w/other birth disorders or syndromes
 A syndrome is a set of physical, developmental, & sometimes behavioral traits that occur together.
 Clefts have been identified as 1 feature in over 450 craniofacial disorders
 50% of children w/cleft palate only, submucous, or non-cleft VPI have a syndrome w/other associated anomalies
 Association: Patients w/craniofacial disorders may undergo genetic testing & determine that there is not an
identified syndrome. These children may have a pattern of multiple malformations seen in many individuals,
however, w/no known genetic cause.
 Sequence: Some children may have multiple anomalies that occurred as a result of a sequence & not as a result of
a syndrome. This is a series of multiple anomalies that results frm a single initiating malformation event or
mechanical factor.
o Ex: Pierre Robin sequence: the lack of normal forward growth of the mandible in the embryo keeps the
tongue up between the palatal shelves which causes a cleft because the palatal shelves do not close the
tongue is pushed downward into the mandible but remains elevated & retracted in a jaw that is too small
 The majority of isolated clefts appear to be caused by an interaction between an indiv. genes (genetic
predisposition) & certain environmental factors
 Genes contain DNA, which provides each person w/his or her own unique human characteristics. They account
for factors such as height, eye color, & physical appearance. They also determine things such as the number of
fingers on the hand & the shape of your face.
 Genetic disorders may be considered genetic even if there are no other family members w/clefts
 Genetic disorders occur when:
o something happens to change a gene (mutation);
o an individual inherits a disordered gene frm one or both parents who may or may not know they have the
gene;
 o or an individual inherits multiple genes
• When used by geneticists, the term “environmental” refers to all those factors that are not in the genes &
chromosomes. It is a very broad definition that includes things such as exposure to drugs, chemicals, & infectious
agents.
• A woman may not even know that she is pregnant at this point. To cause a cleft lip or cleft palate, an
environmental exposure must have occurred before the formation of these structures. Anything that happened
after this time has no bearing on the cause of the cleft.
• The risk for recurrence of a cleft condition is determined by a number of factors that are often unique in a
particular family. These include:
o The number of family members w/clefts
o How closely related these people are
o The race & sex of the affected individuals
o The type of cleft each person has.
• After a syndrome is excluded, recurrence risk counseling for cleft lip and/or palate can be offered to families.
There is no genetic test currently available to determine a person’s individual chance of having a child w/a cleft
but rather a percentage range can be provided detailing the indiv. risk based on the variables discussed in the
previous slide
Genetics
• Every parent has approximately a 1 in 600 risk of having a child w/a cleft
• Once parents have a child w/ a cleft, the risk that the next child & each succeeding child will be affected is 2-5%
• If there is more than one person in the immediate family w/a cleft, the risk rises to 10-12%
• An individual w/a cleft who is the only one in his/her family w/a cleft has a 2-5% chance that his or her child will
have a cleft
• If the individual w/the cleft also has a close relative w/a cleft the risk increases to 10-12% that a child will have a
cleft.
• Finally, the unaffected siblings of an individual w/a cleft have a roughly 1% risk of having a baby w/a cleft. This
risk may rise to 5-6% if more than 1 close family member has a cleft
• If a syndrome is involved, the risk for recurrence within the family could be as high as 50%
Genetic Evaluation
A genetic evaluation provides specific information for a particular family.
Most evaluations involve several steps including:
a. A detailed family history,
b. A medical history,
c. A physical examination of the individual w/the cleft,
d. Lab testing when there is a suspicion that the cleft may be part of a syndrome
e. Explanation of test results
f. Explanation of familial recurrence of inherited conditions
g. Provide supportive counseling. Sometimes lab testing may need to be repeated if enough time has passed &
there's still suspicion for an underlying syndrome as tests can become more sensitive over time. Some families
will undergo genetic testing & not revisit w/the genetics counselor until the child is of childbearing age
themselves for re-explanation for risk for recurrence.
Inheritance
Autosomal Dominant: Single gene transmitted directly frm parent to 50% of their offspring.
Autosomal Recessive: Single gene disorder not evident in a carrier. If both parents have the same recessive trait 25% of
their offspring will exhibit the trait, 50% will be carriers of the trait.
Genetics
Phenotype: Appearance and/or behavioral characteristics; what we can see clinically. Ex. height, blood type, eye color,
freckles, & hair color. However, phenotypes aren't just physical traits, behaviors are also considered a phenotype which
can include the characteristic cognitive, personality, & our psychiatric pattern that typifies a disorder.
Phenotype Example
Phenotype for Velocardiofacial Syndrome:
a. velopharyngeal insufficiency
b. Cardiac anomalies
c. Learning disabilities
d. Facial features (long face, widely spaced eyes, almond shaped eyes, flat nasal bridges, bulbous nose, no upper lip
definition, low tone)
e. Long tapered fingers
Multi-Anomaly Disorders
 Important for the SLP to be able to recognize the possible presence of a multi-anomaly disorder in a patient.
Many mild cases are likely to be missed
 Patients who appear to have minimal physical involvement ma exhibit significant functional difficulties (ex:
cognition, communication skills)
 If the clinician focuses too much on the visible problems, we may miss the less obvious problems (ex: hearing
loss, cardiac condition)
Syndromic vs. Non-Syndromic
 As we learned, there is a probability that additional anomalies will be present in a child w/a cleft
 Most cases of a cleft lip with/without cleft palate are isolated & nonsyndromic
 More than 50% of cases of cleft palate & 25% of cleft lip & cleft palate are syndromic, meaning that they are
usually associated w/other birth defects. Therefore, there's a high chance of a child having a syndrome if the
palate is involved.
Be Observant & Descriptive of Facial Features
 Eyes: check for hyper/hyperteleorism, if they are spaced widely or narrowly
 Ears: check to see if they are rotated, set too high or low, or if they're protruding.
 Nose: check to see if the bridge is flattened or bulbous.
 Lips: ex. check for lip pits (Van der Woude syndrome).
 shape of the head: note craniosynostosis (is a disorder present at birth in which one or more of the fibrous joints
between the bones of your baby's skull (cranial sutures) close prematurely (fuse), before your baby's brain is fully
formed. Brain growth continues, giving the head a misshapen appearance.)
 symmetry of the face: ex. check for facial asymmetry which can be present w/Goldenhar syndrome.
Velocardiofacial Syndrome
 Velocardiofacial syndrome is the most frequently occurring syndrome involving either overt clefts or non-cleft
problems in velopharyngeal function
 It may be the most frequent occurring syndrome to be found on SLP caseloads.
 Shprintzen first reported 1978
 Autosomal dominant disorder
 Velar clefting or dysfunction
 Dysmorphic facies w/reduced facial expression
 Conotruncal heart defects
 Learning disabilities (e.g., ADD, ADHD)
 Linked genetically to 22q 11 deletion. This was first detected by fish testing
 Recent research shows the mean age of diagnosis is 9.2 years of age. We know that VCFS can not only impact
speech & ultimately communication effectiveness, but it can also contribute to learning difficulties in school. If
identified early, the child would have a better prognosis for academic & communication success.
VCFS Facial Dysmorphology
Variable Phenotypes:
 Long Facies (a long & narrow face)
 Vertical maxillary excess (excessive maxillary development in the vertical plane which results in a gummy smile.
An ideal treatment for this is the reduction of the maxillary dimension by Le Fort One osteotomy.)
  Bulbous nasal tip (as a result of misshapen cartilage that form & support the tip of the nose & can be corrected
w/rhinoplasty if desired.)
 Narrow palpebral fissures (are the opening between the eyelids)
 Almond shaped eyes
 Small, downturned oral commissures (corner of mouth. Are important not only in facial appearance but
particularly w/functions such as smiling.).
 Overfolded helix (outer rim of the ear)
 Protuberant cup-shaped ears
 Minor auricular anomalies. (deformations of the ear)
VCFS Medical Conditions (Variable)
 Conotruncal cardiac anomaly (82%)- even if just a heart murmur
 Umbilical hernia (23%)
 Hypospadias (where the opening of the penis is on the underside rather than the tip) (10% of males)
 Hypotonia in infancy
 Constipation
VCFS Anatomical Variations
 Slender, hyperextensive fingers
 Small stature
 Medial displacement of internal carotid arteries (25%) - this is important to know particularly when referring for
pharyngoplasty for VPI management
 Overt cleft of the palate (39%)
 Submucous cleft palate (21%) - results frm a lack of normal fusion of the muscles within the soft palate when the
baby is developing in utero.
 Velopharyngeal Incompetence (97%) - is one of the most common features of this syndrome.
 Deep pharynx due to more obtuse cranial base angle. Makes it difficult for the velum to contact the posterior
pharyngeal wall w/speech production.
 pharyngeal flap
o is the most frequently used approach to treating VPI. Although centrally placed flaps require movement in
the lateral pharyngeal walls to work effectively & w/the presence of a hypodynamic sys. VPI is still a risk.
 velopharyngeal imaging & surgical planning
o should be conducted when a few oral stop consonants can be produced so assessment of true VP inadequacy
is possible. If the child's speech production consists of rampant consonant deletion or glottal stops an
accurate assessment cannot be obtained. Children w/VCFS seem to take longer to adapt their anatomy & VP
physiology following pharyngoplasty procedures likely secondary to slower & less coordinated motor
development. It may require speech therapy to educate & implement compensatory speaking strategies for
adequate velar speed & coordination which can result in improved VP closure.
Behavioral Characteristics of VCFS
 Socialization difficulties (almost all aspects of language learning, speech production, & cognitive development
are affected by VCFS which likely contributes to this.)
 Short attention span (e.g., ADD, ADHD)
 Learning difficulties
 Psychotic symptoms in adolescence (25%) - the most common disorder is schizophrenia.
Speech Disorders of VCFS
Combination of cognitive problems, delayed acquisition of speech & language developmental milestones, possible
hypotonicity of facial muscles, possible conductive hearing loss due to recurrent OME, & the high likelihood of problems
in velopharyngeal function supply a basis for problems in phonetic development. These children have a high likelihood
of being present on your caseload & therefore having a fundamental understanding of the syndrome is important to
ensure the best possible care.
Importance of Early Diagnosis
 Will allow for appropriate intervention for feeding to ensure successful early feeding.
 Can provide possible explanations for learning difficulties & allow for interventions to be put in place to support
academic success.
 Can also allow for early speech intervention to decrease the use of learned compensatory articulation patterns,
which are difficult to break & negatively impacts speech intelligibility.
 Diagnostic imaging can be completed to assess replacement of carotids as replacement poses a risk for
pharyngoplasty.