comd 472 PPT 8 Cleft Characteristics, Classifications, Etiology, Genetics and Syndromes, Velopharyngeal Dysfunction

Embryologic Development

This is dependent on the formation of the neural crest cells in the embryo. The neural crest cells originate from the area around the neuropore and migrate at different rates.

Facial Prominences - 4th week

This contains 4 processes:

• frontonasal process

• maxillary process

• medial nasal process

• mandibular process

Frontonasal process

This forms forehead, bridge of nose, medial and lateral nasal prominences 

Maxillary processes

This forms cheeks and lateral portions of the upper lip 

Medial nasal processes

This forms the nasal septum, philtrum, premaxilla, and the primary palate 

Mandibular process

This forms the lower lip 

Lip and Alveolus Development

This begins at 6-7 weeks and starts with the incisive foramen, moving anteriorly to form the alveolus through the fusion of the bilateral incisive suture lines. It then proceeds to form the base of the anterior nose and the upper lip, and the median and two lateral lip segments fuse to form the philtrum and philtra lines.

Endogenous factors contributing to cleft

These are factors inside the body that affect how the palate develops

Chromosomal disorders

These are abnormalities in chromosomes that can interfere with normal palatal development.

Genetic disorders

These are inherited genetic changes that may affect the formation of the palate.

Multifactorial reasons

Palatal development problems can result from a combination of genetic and environmental factors. A person may have a genetic predisposition (increased likelihood) and environmental factors can trigger or contribute to the condition.

Exogenous factors

These are outside influences that can interfere with normal palate development during pregnancy.

Teratogens

These are any substance, infection, physical agent, or maternal health condition that can disrupt normal fetal development and lead to birth defects, growth restriction, miscarriage, or stillbirth

Viruses during pregnancy

Certain maternal infections may interfere with normal development.

Nutritional deficiencies during pregnancy

The lack of important nutrients, especially maternal vitamin B6 and folic acid, may increase the risk of developmental abnormalities.

Maternal age

The age of the mother may influence pregnancy and developmental risks. Male embryo develop earlier and faster than female embryo. Female embryo are more susceptible to damage due to their longer gestational time.

Mechanical interference with development

These are physical factors that may prevent the palate from fusing properly, such as:

• A cyst rupturing at the site where the palate should fuse.

• Overcrowding in the developing oral cavity.

• Abnormal tongue positioning that interferes with the joining of the palatal shelves.

Veau Classification (1931)

• Veau Class I: isolated soft palate cleft

• Veau Class II: isolated hard and soft palate cleft 

•  Veau Class III: unilateral CLAP

• Veau Class IV: bilateral CLAP

This does not have a classification for the isolated cleft lip.

Kernahan and Stark (1958) primary palate

This is the prepalatal or intermaxillary segment that is anterior to the incisive foramen and includes the lips and alveolus.

Clefts here include:

• complete

• incomplete

• unilateral

• bilateral

Kernahan and Stark (1958) primary palate complete cleft

This is through the lip, nostril sill, and alveolus to the incisive foramen

Kernahan and Stark (1958) primary palate incomplete cleft

This is as minor as a small, subcutaneous notch in the vermilion, or the entire lip, but not the alveolus.

Kernahan and Stark (1958) primary palate unilateral cleft

This occurs on the right or left side, but most often on the left side.

Kernahan and Stark (1958) primarily palate bilateral cleft

This is a cleft on both sides of the upper lip.

Kernahan and Stark (1958) primarily palate prolabium

This is the tissue that normally forms the middle part of the upper lip (philtrum) that is completely separated and forms an isolated pieces

Kernahan and Stark (1958) primarily palate complete bilateral cleft

This separation extends through the prolabium and sometimes causes the premaxilla to protrude significantly.

Kernahan and Stark (1958) secondary palate

This occurs behind the incisive foramen and can involve the hard palate, soft palate, or both. A complete cleft extends through the hard palate to the incisive foramen, while an incomplete cleft affects only part of the soft palate (velum). Clefts can also be submucous, unilateral, or bilateral.

Kernahan (1971)

This is a more detailed system used to identify the location and severity of cleft lip and palate. The Y-shaped diagram is numbered 1–6 for the primary palate (lips and alveolus) and 7–9 for the secondary palate (hard and soft palate); affected areas are shaded, while submucous clefts are marked with crosshatching.

Kriens “LAHSHAL” (1987)

This describes the location, size, extent, and type of a cleft using letters that represent the lip, alveolus, hard palate, and soft palate from right to left. Capital letters indicate a complete cleft, lowercase letters indicate an incomplete cleft, and a period or dash indicates a normal, unaffected area.

ACPA system

This is similar to the Kernahan and Stark classification systems

Pittsburgh Fistula Classification System (2007)

This identifies the location of openings (fistulas) in the palate. It uses Types I–VII to classify fistulas based on their location, ranging from the uvula and soft palate to the hard palate and alveolar regions.

Genetic components to cleft deoxyribonucleic acid (DNA)

This is a substance that carries hereditary information. It is organized into chromosomes that act as chemical building blocks linked together as a “double helix” (coiled ladder). These strands are held together by hydrogen bonds.

Genetic components to cleft replication

This is the ability for one DNA molecule to make two identical molecules. the double strand contains one original and one complementary new strand and are carefully controlled, proofread, and repaired by the body to preserve the sequence

Genetic components to cleft chromosome

This is a single linear double strand of DNA that organizes and regulates gene activity. Each human has 22 sets of chromosomes, or autosomes, plus 1 set of sex chromosomes, “X and Y”, that determine sex

• Two X = female 46, XX

• X from mother and Y from father = male 46, XY

Genetic components to cleft genes

These are functional units of the longer DNA strands that contains a discrete segment of DNA residing in a chromosome

Genetic components to cleft ribonucleic acid (RNA)

This carries genetic instructions from DNA to the cell's protein-making machinery so proteins can be produced.

Mitosis

This is the process of cell division that occurs in somatic (regular body) cells. During this process, duplicated chromosomes separate so that each new cell receives an identical set of DNA. The process takes approximately one hour, and each daughter cell ends up with the same number of chromosomes as the parent cell (46 in humans).

Meiosis

This is a type of cell division that produces gametes (reproductive cells), including sperm and eggs. Spermatocytes are developing male reproductive cells, while oocytes are developing female reproductive cells. During this process, the chromosome number is reduced by half, leaving each sperm and egg with 23 chromosomes.

Chromosomal Abnormalities

These occur when a person has an extra or missing copy of a chromosome due to an error during meiosis. This often happens through nondisjunction, which is when chromosomes fail to separate properly during cell division, resulting in cells with an incorrect number of chromosomes.

Monosomy

occurs when a person is missing one copy of a chromosome instead of having the normal pair.

Turner syndrome (Monosomy X)

This is the only complete monosomy commonly compatible with live birth and can cause short stature, a webbed neck, and delayed or absent sexual maturation.

Trisomy

This occurs when a person has an extra copy of a chromosome, resulting in three copies instead of the normal two. Examples include Trisomy 21 (Down syndrome), Trisomy 13 (Patau syndrome), and Trisomy 18 (Edwards syndrome), which can cause severe birth defects and shortened life expectancy; Trisomy 13 is associated with cleft lip and palate (CLAP), while Trisomy 18 can be associated with Pierre Robin sequence and cleft palate (CP).

Mendelian Inheritance - Mendel (1866)

This is the basic pattern of how traits are passed from parents to children through genes, with one copy of each gene inherited from each parent. Genes can have different versions called alleles, which can be dominant (masking the effect of another allele) or recessive (usually expressed only when two recessive copies are inherited).

Autosomal Recessive Inheritance

This occurs when a person inherits two copies of a mutated gene, one from each parent, resulting in the condition. A person who inherits only one mutated copy is called a carrier and typically does not show symptoms because they also have one functioning copy of the gene.

X-linked inheritance

This occurs when a genetic condition is caused by a mutated gene located on the X chromosome. Females are generally less likely to be affected because they have two X chromosomes, meaning a healthy copy may compensate for the mutated one.

Non-Mendelian inheritance

This refers to patterns of genetic inheritance that do not follow the simple dominant and recessive rules of Mendelian genetics.

Multifactorial inheritance

This occurs when traits or conditions are influenced by multiple genes working together along with environmental factors.

Purpose of a genetic evaluation

This is used to identify and diagnose genetic conditions, understand the medical and family history of the condition, and determine the chances of it occurring again in future pregnancies. It also provides genetic counseling and support to help individuals and families understand their condition and make informed decisions.

Elements of a genetic evaluation

These include reviewing the prenatal history, the newborn’s medical and feeding history, the child’s development, and the family’s medical history. A physical exam and laboratory studies help identify possible genetic conditions, while genetic and psychosocial counseling provide families with information, guidance, and emotional support.

Syndrome

This is a group of symptoms or abnormalities that occur together and appear to be related to one another.

Syndrome sequence

This is a series of abnormalities caused by one initial problem or mechanical factor, such as the Pierre Robin sequence.

Syndrome association

This is a group of abnormalities that commonly occur together but have no known cause or explanation.

Apert syndrome (Acrocephalosyndactyly Type 1)

This is an autosomal genetic condition characterized by premature fusion of the skull bones (craniosynostosis), webbed or fused fingers and toes (syndactyly), and bulging eyes (exophthalmos). It can also cause cleft palate, conductive hearing loss, brain abnormalities, and cognitive impairment, with hearing problems potentially related to abnormal fixation of the middle ear bones.

Crouzon syndrome

This is a genetic condition characterized by premature fusion of the skull bones (craniosynostosis), underdevelopment of the midface, and shallow eye sockets that cause the eyes to bulge; some individuals may also have an absent or underdeveloped ear canal (auditory meatus). Communication difficulties vary depending on the amount of palate involvement, how misaligned the oral structures are, and the type and severity of hearing loss.

Fetal alcohol syndrome (FAS)

This occurs when a baby is exposed to alcohol before birth, potentially causing facial abnormalities, poor growth, and brain or central nervous system problems. It can lead to communication difficulties such as delayed speech and language, poor articulation, slurred speech, voice and fluency problems, hearing disorders, and difficulties with attention, memory, and learning.

Treacher Collins syndrome

This is an inherited autosomal dominant condition that causes underdevelopment of the facial bones, especially the midface, as well as small or abnormally formed ears (microtia) and sometimes a cleft palate. It can lead to conductive hearing loss and speech and language difficulties because of the facial and ear abnormalities.

Van der Woude syndrome

This is an autosomal dominant genetic condition and the most common syndromic cause of cleft lip and cleft palate (CL/CP), accounting for up to 3% of cleft lip cases. Individuals typically have normal overall development, but may experience speech and communication difficulties related to their cleft palate.

Stickler syndrome

This is a genetic condition and one of the most common identifiable causes of cleft palate, often associated with Pierre Robin sequence, a small lower jaw (micrognathia), nearsightedness (myopia), early-onset arthritis, and sensorineural hearing loss. Overall development is typically normal, but communication difficulties may occur due to cleft palate-related speech problems and hearing loss.

Velocardiofacial syndrome (VCFS)

This is an autosomal dominant genetic condition that can cause abnormalities of the palate, heart, blood vessels, and facial structure, including a long face, small jaw, and possible Pierre Robin sequence. Communication difficulties may include hypernasality, velopharyngeal insufficiency (VPI), speech motor planning problems (verbal apraxia), hearing loss, and developmental delays.

Velopharyngeal function

This depends on several paired muscles working together to close the opening between the nasal cavity and the throat during speech and swallowing.

• Levator veli palatini*

• Superior Pharyngeal Constrictor* 

• Musculus Uvulae

• Palatopharyngeus

• Palatoglossus*

• Tensor Veli Palatini

• Stylopharyngeous

Velopharyngeal function levator veli palatini* muscle involvement

This is the main muscle responsible for lifting the soft palate upward and backward toward the pharyngeal wall. It plays the most important role in achieving velopharyngeal closure.

Velopharyngeal function superior pharyngeal constrictor muscle involvement

This muscle helps move the pharyngeal (throat) walls inward to assist in closing the opening between the nose and throat.

Velopharyngeal function musculus uvulae muscle involvement

This muscle shortens and thickens the soft palate and uvula, helping create a better seal against the back of the throat.

Velopharyngeal function palatopharyngeus muscle involvement

This muscle helps lower the soft palate and elevate the pharynx during swallowing. It also helps coordinate movement of the palate and throat.

Velopharyngeal function palatoglossus muscle involvement

This muscle connects the soft palate to the tongue and helps lower the soft palate while elevating the back of the tongue. It acts opposite to the levator veli palatini.

Velopharyngeal function Tensor Veli Palatini muscle involvement

This muscle tightens and stretches the soft palate, helping prepare it for proper movement and opening the Eustachian tube to equalize middle ear pressure.

Velopharyngeal function stylopharyngeous muscle involvement

This muscle elevates and widens the pharynx during swallowing and speech, helping coordinate throat movement.

Velopharyngeal function physiology

This describes how the soft palate (velum) and throat walls work together to close off the nasal cavity during speech and swallowing. When inactive, the velum rests low in the throat against the back of the tongue, but when active, it elevates to meet the posterior and lateral pharyngeal walls to create a seal. The lateral walls move inward to help with closure, while the posterior wall may move forward and form a structure called Passavant’s pad, which can assist in velopharyngeal closure.

Velopharyngeal variable closure

This means that the amount and timing of soft palate and throat movement can vary among normal speakers. The velopharyngeal valve must close just before voice production (phonation) to prevent air from escaping through the nose during oral speech. Speaking too quickly can make it harder to coordinate proper closure, while slower speech allows more time for coordination; fatigue can also affect muscle performance, and cluttering (rapid, irregular speech) may contribute to timing and coordination difficulties.

The severity of cleft on the primary palate

This affects the lip, alveolus (gum), and nostril, with severity ranging from a complete cleft involving all three structures to an incomplete cleft that may appear as a small notch in the lip without affecting the alveolus. A unilateral cleft affects one side (usually the left) and may cause a shortened columella (the tissue between the nostrils), while a bilateral cleft affects both sides and results in an isolated middle portion of the upper lip called the prolabium.

The results of cleft on the primary palate

These can cause deformities of the nasal cavity, reducing the nasal airway and potentially leading to nasal obstruction or stenosis (narrowing of the airway). The nose may continue to grow but remain smaller than a typical nose, and lip repair can sometimes worsen nasal obstruction. These structural changes can also contribute to abnormal resonance, dental problems, bite misalignment (malocclusion), and articulation errors that affect speech production.

The effect of complete cleft on the secondary palate

This extends through the uvula and soft palate (velum), follows the midline of the hard palate, and reaches the incisive foramen.

The effect of incomplete cleft on the secondary palate

This may only involve a bifid uvula (split uvula) or extend farther into the soft palate without involving the entire hard palate.

The effect of unilateral cleft on the secondary palate

the vomer bone (part of the nasal septum) connects to the larger palatal segment

The effect of bilateral cleft on the secondary palate

In this, the vomer does not attach to either palatal segment.

The results of cleft on the secondary palate

With a cleft palate, the muscle origins are usually normal, but the muscle insertions are abnormal. In a typical cleft (Veau cleft), the levator veli palatini (LVP) and palatopharyngeus muscles attach to the back edge of the hard palate instead of forming a functional muscle sling across the soft palate.

The goal of surgery is to reposition the muscles to create normal velopharyngeal function. However, muscle size and attachment points can still vary after surgery, and a complete cleft may involve an absent palatal aponeurosis (connective tissue layer), resulting in a shorter soft palate after repair and difficulty achieving proper VP closure.

The conditions and functional problems of cleft on the secondary palate

A cleft here can cause defective speech, abnormal resonance (especially hypernasality), and nasal regurgitation (food or liquid coming through the nose). Individuals also have a higher risk of otitis media (middle ear infections) because the Eustachian tube may not function properly.

The tensor veli palatini (TVP) muscle normally helps open the Eustachian tube to equalize pressure in the middle ear, but cleft-related muscle abnormalities can interfere with this function.

Submucous cleft palate

This occurs when the muscles underneath the lining of the soft palate are not properly joined, even though the surface tissue appears intact.

Overt submucous cleft

This can be identified during an oral-peripheral mechanism (OPM) exam by signs such as a bifid uvula (split uvula) and a zona pellucida (bluish or gray discoloration of the soft palate).

Occult submucous cleft

This is hidden and cannot be seen by looking inside the mouth, so it may require nasopharyngoscopy to identify.

The results and functional effects of a submucosal cleft

Some people experience normal velopharyngeal function, normal speech, and no nasal regurgitation or middle ear problems. Others may experience velopharyngeal dysfunction, resulting in poor VP closure, hypernasality or other resonance problems, nasal regurgitation, and middle ear disease.

Treatment for submucosal cleft

An adenoidectomy (removal of the adenoids) is generally not recommended because the adenoids may help the soft palate achieve closure; removing them can worsen velopharyngeal insufficiency. Surgical repair (palatoplasty) is only recommended when there is evidence of velopharyngeal dysfunction rather than simply because a submucous cleft is present.