“Fusion? Pfft. We’d rather make history!” declared the medial nasal processes.

And so, clefting was born—a gap not only in the developing palate but in the hearts of speech therapists everywhere.

Fusion Fumbles and Speech Stumbles
Now, when these tiny rebels refuse to join forces, chaos ensues. The velopharynx—a fancy name for the barrier between the nose and mouth—ends up with a few, shall we say, drafty construction errors. Air escapes, speech gets funky, and suddenly, “baby babble” sounds like a wind tunnel experiment gone wrong.

Enter the surgeons, the unsung heroes of tiny palates everywhere. Their mission? To bring order to the mayhem and ensure that future toddlers don’t accidentally sound like they’re narrating their own ghost stories.

A Historical “Patchwork” Approach
In 1865, Passavant was the first brave soul to attempt fixing the velopharynx by—wait for it—sticking the soft palate to the back of the throat. It’s the medical equivalent of solving a door draft problem with duct tape.

Then came Sloan in 1875 with the pharyngeal flap, followed by Padgett in 1930, who made it official in the U.S. The problem? If you don’t size it right, congratulations! You’ve now upgraded from speech issues to obstructive sleep apnea. Talk about overachieving.

Surgical Glow-Ups and the Quest for the Perfect Fix
Wilfred Hynes in 1950 got creative with myomucosal flaps, because nothing says “innovation” like rearranging muscles with names longer than your prescription list.

The technique kept evolving, because, let’s be real—every surgeon wants to leave their mark. Jackson, Silverton, and Riski all came in with their own spin, probably in a fierce game of “Whose Flap Is It Anyway?”

And then there was posterior pharyngeal wall augmentation—the surgical version of “filling in the blanks.” Early attempts included Vaseline (yes, really) and a parade of materials like porous polyethylene, collagen, and even calcium hydroxyapatite. Because when in doubt, throw some fancy-sounding stuff at it and hope for the best.

Velopharyngeal Anatomy: The Hidden Orchestra of Speech 🎤🎼

🎻 Levator Veli Palatini: The Conductor
Imagine a maestro standing center stage, arms raised, ready to lead the symphony. That’s the levator veli palatini—responsible for lifting the velum like a curtain, sealing off the nasal and oral cavities. Originating from the petrous part of the temporal bone, its fibers cross in the middle, forming a muscular sling. One contraction, and voilà! The velum retracts at a dramatic 45-degree angle to close the velopharyngeal port.

Translation: Without this guy, your words would sound like they were broadcast from inside a wind tunnel.

🎤 Musculus Uvulae: The Backup Singer
Tucked inside the levator’s muscular sling is the musculus uvulae, a tiny but mighty performer. Unlike other muscles, it has no external attachments—it’s a self-sufficient diva that adds bulk to the velum, fine-tuning closure and ensuring speech clarity.

Think of it as the vocal reverb effect for your natural sound system.

🎺 Tensor Veli Palatini: The Stage Crew
What’s a good performance without proper sound balance? Enter the tensor veli palatini, responsible for opening the Eustachian tube during yawning and swallowing. Its tendon takes a dramatic turn around the hamulus of the medial pterygoid plate, ensuring proper ear drainage and pressure equalization.

Fun fact: In cleft palate cases, this muscle’s dysfunction is why kids get chronic ear infections—basically, a feedback loop of middle ear fluid that even the best sound engineers (otolaryngologists) struggle to fix.

🥁 Superior Pharyngeal Constrictor: The Percussionist
Finally, we have the superior pharyngeal constrictor, a multitasking powerhouse made up of four muscle segments (pterygopharyngeal, buccopharyngeal, mylopharyngeal, and glossopharyngeal). It provides the lateral and posterior walls of the pharynx, tightens during speech, and even forms Passavant’s ridge, a temporary bulge that helps close the velopharyngeal port.

In simple terms, it’s the drummer keeping the beat, ensuring speech stays rhythmic and not riddled with air leaks.

🏋️ Palatopharyngeus: The Weightlifter
Muscle Motto: “No food left behind!”

The palatopharyngeus is your posterior tonsillar pillar’s personal trainer. This vertically-oriented muscle starts at the soft palate, extends to the pharyngeal walls and thyroid cartilage, and has one big job—preventing food from making an unscheduled detour into your nasopharynx.

💪 Workout Routine:
✅ Pulls lateral pharyngeal walls inward (creating the Passavant ridge).
✅ Assists the levator veli palatini in velopharyngeal closure.
✅ Helps push food down like a conveyor belt at an airport security check.

Without it, your food might just take a U-turn and end up where it doesn’t belong (hello, awkward nose sneezes).

🏃 Palatoglossus: The Yoga Instructor
Muscle Motto: “Balance is everything.”

The palatoglossus loves flexibility—literally. Found in the anterior tonsillar pillar, it connects the velum to the tongue and works as a direct antagonist to the levator veli palatini.

🧘 Workout Routine:
✅ Lowers the velum (undoing the lift from levator veli palatini).
✅ Helps open the velopharyngeal port for breathing and speech.
✅ Elevates the back of the tongue—because someone has to push food toward the esophagus.

This muscle is basically the chill mediator in the gym, making sure the soft palate and tongue don’t get into a tug-of-war.

🚴 Salpingopharyngeus: The Gym Regular (But No One Knows Why)
Muscle Motto: “I’m just here for the vibes.”

The salpingopharyngeus shows up to the gym but doesn’t seem to have any major responsibilities. It originates near the Eustachian tube and hangs out with the palatopharyngeus, but its function is… well, kind of optional.

🤷 Workout Routine:
✅ Moves the pharynx a little.
✅ Sort of helps with swallowing.
✅ Exists.

Basically, it’s like that guy in the gym who always stretches but never actually lifts anything.

⚡ Nerve Trainers: Keeping the Gym in Check
🧠 Vagus Nerve (Pharyngeal Plexus) – The Boss
✅ Controls levator veli palatini, palatopharyngeus, salpingopharyngeus, and all pharyngeal constrictors.
✅ Makes sure velopharyngeal closure happens (otherwise, you’d sound permanently nasal).

🧠 Mandibular Division of Trigeminal Nerve – The Specialist
✅ Only works on tensor veli palatini (because even the velum needs a specialist for ear pressure equalization).

With these muscles working together, you get clear speech, safe swallowing, and minimal nasal food disasters. But if even one muscle skips leg day (or, in this case, velopharyngeal closure day), things can get messy fast.

So, next time you speak, eat, or yawn, thank your Velopharyngeal Team—they’re always working out, even when you’re not!

The Architectural Flaws and Functional Fixes
Think of the velopharyngeal port as a soundproof door between the nasopharynx and oropharynx. In a normal setup, the levator veli palatini acts like a hinge, lifting the velum to close the door for clear speech. But in cleft palate, that hinge is broken—or rather, misaligned—leading to some major structural and functional issues.

🏗️ What Goes Wrong in Cleft Palate?

Levator Veli Palatini’s Great Misplacement

Normally, this muscle runs horizontally to pull the velum up and back, sealing off the nasopharynx.
In cleft palate, the muscle is discontinuous and positioned longitudinally, inserting onto the hard palate instead.
🚨 Consequence? The velum can’t reach the posterior pharyngeal wall, causing velopharyngeal insufficiency (VPI).
💬 Result? Hypernasal speech and air leakage through the nose while speaking.

The Tensor Veli Palatini’s Failed Pulley System

Normally, the tensor veli palatini works with the levator veli palatini to open the Eustachian tube, preventing middle ear infections.
In cleft palate, the levator’s faulty position disrupts this mechanism, leading to:
✅ Chronic ear infections (otitis media)
✅ Hearing loss (affecting 10–30% of cleft patients)

🎤 How Velopharyngeal Closure Happens (or Doesn’t)
Velopharyngeal closure is like sealing off a room for perfect acoustics—except that people use different methods to achieve it:

🔵 Circular Closure → The Team Effort

The velum and pharyngeal walls both contribute equally.
Ideal for balanced speech production.

⚫ Coronal Closure → Velum-Dominant Approach

The velum does most of the work, moving backward to close the port.
Most common pattern in normal speakers.

🟡 Sagittal Closure → Pharyngeal Walls Take Over

The lateral pharyngeal walls move toward the midline, with less velar involvement.
Less common but seen in some individuals.

👂 Why Does This Matter?

In cleft palate patients, the closure mechanism is often compromised.
Depending on the severity of clefting, surgical correction aims to restore muscle positioning and improve velopharyngeal function.

Velopharyngeal Insufficiency (VPI) vs. Velopharyngeal Incompetence (VPC)

Velopharyngeal dysfunction (VPD) is an umbrella term for abnormal nasal airflow during speech, leading to hypernasality and articulation issues. It can be categorized into:

Velopharyngeal Insufficiency (VPI) – A structural problem where the velopharyngeal port cannot close properly due to an anatomical defect.
Velopharyngeal Incompetence (VPC) – A neuromuscular issue where the structures are intact, but they fail to function properly due to neurological conditions.

📌 Velopharyngeal Insufficiency (VPI): Structural Roadblock

Common Causes:
✅ Cleft Palate (Overt/Submucosal) – The levator veli palatini is abnormally positioned, preventing proper closure.
✅ Short Velum Post-Surgery – Even after palatoplasty, the velum may remain too short for complete closure.
✅ Oronasal Fistula – An opening between the mouth and nose, disrupting normal airflow.
✅ Adenoidectomy – Removal of enlarged adenoids can create an enlarged pharyngeal space, causing temporary or permanent VPI.

📌 Velopharyngeal Incompetence (VPC): A Functional Deficit

Common Causes:
✅ Congenital Hypotonia (e.g., Down syndrome, DiGeorge syndrome) – Weak muscle tone in the velopharynx.
✅ Neurological Disorders (e.g., traumatic brain injury, stroke) – Impaired neuromuscular control.
✅ Cerebrovascular Accidents (Stroke) – Disrupted nerve signaling affecting velopharyngeal movement.

📍 Key Difference?

VPI is a structural defect, while VPC is a neurological issue affecting muscle coordination.

🧬 Genetic Associations of Velopharyngeal
Incompetence

Picture this: a tiny segment of Chromosome 22 decides to disappear during DNA replication. Poof! Gone. As a result, a whole range of issues can pop up, including congenital heart defects, immune deficiencies, and—our star of the show—velopharyngeal incompetence (VPI).

VPI is when the velopharyngeal mechanism (aka the soft palate and surrounding muscles) doesn’t close properly, leading to speech that sounds like someone left the nasal door wide open. It’s like your voice is on a permanent speakerphone setting with no mute button.

Speech & The Great Escape: What’s Happening in VPI?
So, why does VPI happen in 22q11.2 deletions? Well, the list is long and full of bizarre anatomical quirks:

Muscle Hypotonia: The velopharyngeal muscles are basically slacking off, leading to poor closure. Lazy much?

Adenoid Hypoplasia: The adenoids are underdeveloped, so they don’t help with closure either.

Platybasia: A fancy term for a flattened skull base, which increases the velopharyngeal gap—kind of like trying to close a door in a frame that’s too wide.

Upper Airway Asymmetry: The palate lifts unevenly, like a seesaw with one side stuck.

Brain Involvement: Studies suggest even the brain structure is different in these individuals—because why should only the throat have all the fun?

The 22q11.2 Speech Struggle
A whopping 69% of individuals with 22q11.2 deletion have a palatal abnormality, ranging from cleft palates to bifid uvulas (which sounds like a cool sci-fi term but is just a split uvula). And 27% develop VPI, making speech therapy a must.

In a nutshell, VPI in 22q11.2 deletion syndrome isn’t just about anatomy—it’s a whole-body mystery that involves muscles, bones, and even the brain. If genes could talk, they’d probably just say, “Oops, my bad.”

So, next time you hear someone with a nasal voice, just know—it might be their genetics doing a disappearing act. Chromosome 22, you mischievous little trickster!

🧬 Candidate Genes for VPI: TBX1 and Beyond

Meet the Usual Suspect: TBX1

If VPI had a prime suspect, it would be TBX1. This little troublemaker is the most commonly deleted gene in 85% of individuals with 22q11.2 deletion syndrome. The other 15%? They like to keep things interesting with “nested deletions” (which is geneticist-speak for plot twists).

But here’s where it gets wild—some patients who don’t have the typical 22q11.2 deletion are rocking extra copies of the region that’s normally missing. That’s right—genetics sometimes decides to duplicate instead of delete, just to keep researchers on their toes.

TBX1: The Gene with a Plan (Sort of…)
Most of what we know about TBX1 comes from mouse studies. And let me tell you, these mice have been through a lot in the name of science. Researchers have been doing gene targeting experiments, and the results are basically a craniofacial nightmare:

Persistent truncus arteriosus (a heart defect that sounds like a spell from Harry Potter)
Microtia (tiny or missing ears)
Pharyngeal abnormalities (aka, VPI’s favorite excuse)
TBX1 is a transcription factor, meaning it bosses around other genes during development. It’s supposed to help form facial muscles, pharyngeal structures, and the palate, but when it goes missing, everything gets thrown into chaos—kind of like when a group project loses its most responsible member.

TBX1 and Its Entourage

But TBX1 doesn’t work alone—it’s got a whole squad of genes working (or not working) alongside it. Let’s meet the supporting cast:

ISL1 & Tcf21: These guys team up with TBX1 in the pharyngeal mesoderm (a fancy way of saying “throat muscle HQ”).
Six1 & Eya1: These two interact with TBX1 to make sure the fibroblast growth factor 8 (Fgf8) does its job. If Fgf8 isn’t happy, craniofacial development takes a serious hit.
Fgf8: The real MVP of face-building. Without enough Fgf8, the velopharyngeal region doesn’t form properly—resulting in speech and swallowing issues.
Basically, if TBX1 is missing, its whole gene friend group gets thrown into disarray. And when the genes aren’t cooperating, the palate and throat muscles end up looking like a half-finished jigsaw puzzle.

If you ever feel like your velum just isn’t pulling its weight, don’t be too hard on it—it’s probably dealing with a genetic crisis. Between TBX1 and its dysfunctional genetic friend group, the whole system is one big, messy group chat of developmental confusion.

On the bright side, research into these genes is ongoing, and the more we understand their roles, the better we can develop treatments for VPI and related conditions.

Until then, let’s just appreciate the genetic drama happening inside every developing face—because, let’s be honest, biology is just reality TV at a microscopic level.

BMP Signaling & Chordin: The Classic Good Cop, Bad Cop Duo
Bone morphogenetic protein (BMP) is that enthusiastic construction worker making sure your craniofacial structures develop. But if BMP isn’t kept in check, things can go overboard, and suddenly, we’re looking at craniofacial anomalies instead of a well-formed palate.

Enter Chordin, the BMP antagonist (aka The Enforcer). Chordin’s job is to keep BMP under control, but when Chordin takes an unexpected vacation (aka a genetic mutation), BMP gets out of hand. The result? Cleft palates, jaw abnormalities, and a whole lot of orthodontic intervention.

And guess what? TBX1, our favorite gene from the 22q11.2 deletion syndrome, is also involved. It turns out that if you mess up both TBX1 and Chordin, the craniofacial drama doubles. Think of it as trying to bake a cake but forgetting both the eggs and the flour. Not a great outcome.

IRF6: The Gene That Decided Your Lips Needed Extra Pits
Meet Interferon Regulatory Factor 6 (IRF6)—a gene that, when working correctly, helps your palate form properly. But when IRF6 goes rogue, it gives us Van Der Woude Syndrome (VWS), an autosomal dominant disorder responsible for cleft lip and palate… and surprise! Lip pits.

Yes, you heard that right. This gene doesn’t just cause cleft palates; it also throws in congenital pits or sinuses on the lower lip—because apparently, it thought your face needed extra pockets. Fun fact: This syndrome makes up about 2% of all cleft lip and palate cases. So if your lower lip has mysterious little dimples, you might just be rocking a genetic signature!

MSX1: The Overachiever Who Forgot to Finish the Job
Msh homeobox 1 (MSX1) is like that one student in class who almost gets full marks but forgets to answer the last question. MSX1 is critical for palatal formation and tooth development, but if it’s mutated, it causes cleft palate and oligodontia (fancy word for missing teeth).

Scientists studied MSX1-deficient mice (because mice always get roped into these things), and their palatal shelves formed, elevated… and then just didn’t fuse. It’s like the gene started the job and then took an extended coffee break. The exact reason? Still a mystery, but it seems related to down-regulated BMP signaling (back to BMP being the root of all trouble).

PVRL1: The Margarita Island Mystery Mutation
Ah, PVRL1, the gene with a backstory straight out of a medical mystery novel. Found on chromosome 11q23.3, this gene is responsible for keeping epithelial and endothelial cells nice and tight—kind of like the glue in your tissues. But when a mutation occurs? Say hello to ectodermal dysplasia Margarita Island type.

This autosomal recessive disorder is named after Margarita Island (off the coast of Venezuela), where there’s a surprisingly high number of people carrying this gene mutation. Affected individuals have cleft lip/palate, ectodermal dysplasia, and partial syndactyly (a.k.a. webbed fingers and toes).

Why is this mutation so common there? Scientists think it might have provided resistance to herpes simplex virus 1 & 2. So, while these folks may have had some serious craniofacial anomalies, at least they were better protected from cold sores. Genetics is wild.

If craniofacial development were a group project, TBX1, IRF6, MSX1, PVRL1, BMP, and Chordin would all be on the team. But, as we all know, in every group project:

One person (BMP) does way too much and messes everything up.
Another (Chordin) tries to control the chaos but can’t keep up.
One (MSX1) almost finishes but forgets the final step.
Another (PVRL1) makes a random decision no one saw coming.
And TBX1? Well, TBX1 just disappears half the time.
So, if your palate is perfectly formed—congrats! Your genetic group project actually turned out well. But if not… just blame your ancestors.