The Short List: Ruling Out the Big Cleft Syndromes
Which specific syndromes must we rule out for Mateo, and what is the one red flag that flags each?
💡 Ruling out a syndrome means checking specific red flags one by one, not forming a general impression.
Prerequisite check
- An is the only apparent anomaly; a is one feature of a broader pattern of findings.
- About 70% of CL/P cases are nonsyndromic and about 30% are syndromic; for only the syndromic share is higher, roughly 50%.
What you will learn
Goal: Students will match each of four high-stakes syndromes (Van der Woude, 22q11.2 deletion, Stickler, ) to its defining red flag and apply the checklist to Mateo to show none of the red flags are present.
- is the most common (about 2% of all patients); its red flag is lower-, often inherited (autosomal dominant, about 50% recurrence).
- presents with or plus a heart defect, low calcium, and immune/thymus problems; it is life-threatening if missed.
- 's red flag is severe eye and ear findings: high myopia with retinal-detachment risk plus hearing loss.
- is plus plus with a wide ; it is a sequence, not a primary syndrome, and can signal Stickler or 22q11.2.
Model: The cleft geneticist's short list, and Mateo run against it
Four syndromes are high-yield because they are common, dangerous, or both, each with a signature red flag (built from the syndrome comparison table). (the most common , about 2% of patients): red flag = pits or small holes in the lower lip (present in about 88% of cases), often with an affected relative; it flips to about 50% (autosomal dominant). (DiGeorge / velocardiofacial): red flag = a heart defect plus low calcium and immune problems (conotruncal cardiac defect, hypocalcemia, thymic/immune deficiency), plus prominent nasal speech; a leading cause of syndromic . : red flag = high myopia with retinal-detachment risk plus hearing loss. : red flag = a very small lower jaw () with the tongue falling back () and airway trouble.
Mateo run against the checklist: no lower- and an unrevealing family history; heart, calcium, and immune screen all normal; no eye or ear findings flagged on the ; normal-sized jaw with no tongue-based and comfortable breathing. His is a complete left CLP with no other anomalies. He trips none of the four red flags on inspection, but that is still an eyeball check, and a tiny deletion makes no visible mark.
Explore (work the model before reading on)
- What is the single red flag for ?
- Which syndrome's red flag is mainly about the heart, calcium, and the immune system?
- and Stickler can overlap. Why might finding and make a geneticist go looking for Stickler's eye and ear findings too?
- Go down the checklist row by row. For each of the four syndromes, is Mateo's red flag present or absent?
- Mateo trips none of the four red flags on inspection. Does a clean checklist run, done by eye, completely rule out every one of these syndromes? Name at least one way a syndrome could still be present that a quick look might miss.
- In one sentence, how does a geneticist turn 'could it be a syndrome?' into something checkable?
Guided notes
The four red flags
- Van der Woude, the most common , red flag = ______ in the lower lip, often inherited.
- 22q11.2 deletion, red flag = a heart defect with low ______ and immune/thymus problems, plus nasal speech.
The other two
- , red flag = high myopia (eyes) and ______ loss (ears).
- , red flag = ______ (small jaw) plus (tongue falls back) and .
Mateo against the list
- Mateo trips none of the red flags: no , no heart/calcium/immune findings, no eye/ear findings, normal jaw and airway.
- That is reassuring, but it is still an eyeball check, and a microdeletion leaves no visible mark, so a lab test may still be needed.
Reading the Research
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Vetted readings for this lesson
- Askarian S, et al. 2022. Genetic factors in cleft lip-cleft palate and clinical utility. Oral Maxillofac Surg. [PMID:35426585]
- Dean KM, Leeper LK. 2020. Management of submucous cleft palate. Curr Opin Otolaryngol Head Neck Surg. [PMID:33105231]
- Hsieh ST, Woo AS. 2019. Pierre Robin Sequence. Clin Plast Surg. [PMID:30851756]
Track your progress today
Check these off as you work through the lesson, then submit. This tells Mr. Mendoza how you're doing so he can help the class. It does not replace turning in your producible.
Use the code Mr. Mendoza gave you, not your name. Saved on this device.
- Read the Model and answered the Explore questions.
- Filled in the guided notes in my own words.
- Defined the new vocabulary with an example.
- Built the producible: Write Mateo's differential note: for each of the four syndromes, state the red flag and write 'present' or 'absent' with the supporting finding, then give a one-line bottom line plus a sentence on what still needs confirming.
- Wrote my Claim, Evidence, and Reasoning exit ticket.
Exit ticket (Claim, Evidence, Reasoning)
- Claim: On the four-syndrome checklist, Mateo's red flags are all ____.
- Evidence: He has no ____ (Van der Woude), no ____ findings (22q11.2), no ____ findings (Stickler), and a normal ____ and airway (Pierre Robin).
- Reasoning: Even so, the question is not fully closed because ____.
| Criterion | Proficient | Developing | Beginning |
|---|---|---|---|
| Complete | Every required part of the artifact is present and filled in. | Most parts are present, but one is missing or left blank. | Several parts are missing. |
| Accurate | The science and data are correct and match the evidence. | Mostly correct, with a small factual slip. | Key science or data is wrong. |
| Scientific reasoning (CER) | States a claim, backs it with specific evidence, and explains the reasoning. | Has a claim and evidence, but the reasoning is thin or missing. | Gives an answer with no evidence or reasoning. |
| Professional communication | Clear, organized, and labeled the way a clinician or scientist would write it. | Readable but disorganized or missing labels. | Hard to follow. |
| Submitted | Turned in the right way (Schoology for routine work) and confirmed. | Turned in, but in the wrong place or unconfirmed. | Not turned in. |
- CompleteProficient: Nothing is left blank: the model fills every part of "Write Mateo's differential note: for each of the four syndromes, state the red flag and write 'present' or 'absent' with the supporting finding, then give a one-line bottom line plus a sentence on what still needs confirming.".
- AccurateProficient: Every number and claim matches the case evidence.
- Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
- Professional communicationProficient: It is organized and labeled like a real chart note.
- SubmittedProficient: It would be turned in on Schoology and confirmed.
Where this leads: careers
What's next: We now have a checklist of red flags, and Mateo trips none of them on inspection. But a checklist you eyeball by hand can miss the quiet ones: a tiny deletion of DNA causes no obvious sign, and subtle features hide. How does the team make the syndromic-versus-isolated call rigorous, with an exam protocol and a test, instead of just a confident glance?