A good genetics Q-bank question isn’t just testing whether you recognize a syndrome—it’s testing whether you can exclude the nearby look-alikes under time pressure. Cri du chat is a classic example: the stem often screams the diagnosis, but the answer choices are designed to lure you into other microdeletions, trisomies, imprinting disorders, and single-gene conditions. Let’s break it down the way you’d want your brain to work on test day.
Tag: Genetics > Chromosomal Disorders & Syndromes
The Vignette (Classic Q-Bank Style)
A newborn has a high-pitched, cat-like cry, microcephaly, hypotonia, and distinct facial features (e.g., round face, hypertelorism, epicanthal folds, micrognathia). The infant has poor feeding and developmental delay. Prenatal history is unremarkable.
Question: Which chromosomal abnormality is most likely?
Correct Answer: Cri du chat syndrome (5p deletion)
What it is
- Deletion of the short arm of chromosome 5:
- A chromosomal deletion syndrome (structural abnormality)
Why the vignette fits
The big clue is the cry.
- High-pitched “cat-like” cry is extremely high-yield and classically tested.
- Caused by laryngeal and neurologic developmental abnormalities.
Other high-yield features (Step 1/2 relevant)
- Microcephaly
- Hypotonia
- Severe developmental delay / intellectual disability
- Distinct facial features: round face, hypertelorism, epicanthal folds, micrognathia
- Congenital heart disease can occur (not as signature as in 22q11, but possible)
Diagnostic testing (how boards may ask it)
| Test | What you’d expect in Cri du chat |
|---|---|
| Karyotype | May show large deletion if sizable |
| FISH / chromosomal microarray | Detects microdeletions (high yield for 5p-, 22q11, etc.) |
Step pearl: If the question mentions “microdeletion” explicitly, think FISH or microarray, not “PCR” or “Southern blot.”
Why Every Answer Choice Matters: Systematic Distractor Takedown
Below are the distractors that frequently show up next to Cri du chat—and the one key feature that should push you away from each.
Distractor 1: Down syndrome (Trisomy 21)
Why they tempt you: developmental delay + hypotonia are common in many syndromes.
How to rule it out quickly
- Down syndrome has upslanting palpebral fissures, single palmar crease, sandal gap, duodenal atresia, endocardial cushion defects, and Brushfield spots.
- The hallmark cat-like cry is not a Down feature.
Genetics high-yield
- Most commonly meiotic nondisjunction (increased maternal age).
- Can also be Robertsonian translocation (e.g., 14;21) → recurrence risk question.
Distractor 2: Edwards syndrome (Trisomy 18)
Why they tempt you: severe developmental issues in a newborn.
How to rule it out
- Think: clenched fists with overlapping fingers, rocker-bottom feet, micrognathia, low-set ears, prominent occiput.
- Often described as IUGR and cardiac/renal defects with high infant mortality.
Key separation from Cri du chat
- Edwards does not have the distinctive cat-like cry.
Distractor 3: Patau syndrome (Trisomy 13)
Why they tempt you: severe congenital anomalies + neurodevelopmental impairment.
How to rule it out
- Classic triad-style clues:
- Holoprosencephaly
- Cleft lip/palate
- Polydactyly
- Also: cutis aplasia, severe cardiac defects.
Key separation
- Patau is more about midline defects and polydactyly, not a laryngeal “cat cry.”
Distractor 4: DiGeorge syndrome (22q11.2 deletion)
Why they tempt you: it’s another microdeletion with facial features and congenital anomalies.
How to rule it out
- Look for CATCH-22:
- Cardiac defects (especially conotruncal: truncus arteriosus, TOF)
- Abnormal facies
- Thymic aplasia → T-cell deficiency
- Cleft palate
- Hypocalcemia (↓PTH) → seizures/tetany
Key separation
- Immunodeficiency + hypocalcemia + conotruncal defects point hard to 22q11, not 5p-.
Distractor 5: Angelman syndrome (maternal imprinting / paternal deletion on 15q)
Why they tempt you: developmental delay + seizures can overlap broadly.
How to rule it out
- Angelman is the “happy puppet”:
- Ataxia, inappropriate laughter/smiling
- Seizures
- Severe speech impairment
- Caused by loss of maternal UBE3A expression in brain (often maternal deletion of 15q11-q13 or imprinting defect).
Key separation
- Behavior phenotype + ataxia are signature; no cat-like cry.
Distractor 6: Prader–Willi syndrome (paternal imprinting / maternal disomy on 15q)
Why they tempt you: hypotonia in infancy is a big Prader–Willi feature.
How to rule it out
- Prader–Willi is two-phase:
- Infancy: hypotonia + poor feeding
- Childhood: hyperphagia, obesity, developmental delay, hypogonadism
- Caused by loss of paternal expression on 15q11-q13 (often paternal deletion).
Key separation
- Hyperphagia/obesity + hypogonadism later is the giveaway; the cry clue points elsewhere.
Distractor 7: Turner syndrome (45,X)
Why they tempt you: congenital heart disease and distinctive features can overlap.
How to rule it out
- Turner: phenotypic female with:
- Short stature
- Webbed neck
- Shield chest with widely spaced nipples
- Streak ovaries → primary amenorrhea, infertility
- Coarctation of the aorta / bicuspid aortic valve
- Not associated with cat-like cry.
Testable genetics
- Often due to nondisjunction or mosaicism.
Distractor 8: Fragile X syndrome (CGG repeat expansion, FMR1)
Why they tempt you: it’s a very common cause of intellectual disability.
How to rule it out
- Fragile X features:
- Macroorchidism (post-puberty)
- Long face, large ears, autism, mitral valve prolapse
- It’s a trinucleotide repeat expansion (anticipation), not a chromosomal deletion syndrome.
Key separation
- Cri du chat is congenital with a neonatal cry clue; Fragile X often becomes clearer later and has a different phenotypic constellation.
High-Yield Summary Table (Fast Review)
| Syndrome | Genetic mechanism | Buzzwords / Key clues |
|---|---|---|
| Cri du chat | Deletion 5p () | High-pitched cat-like cry, microcephaly, hypotonia, developmental delay |
| Down (T21) | Trisomy 21 | Endocardial cushion defect, duodenal atresia, single palmar crease |
| Edwards (T18) | Trisomy 18 | Clenched fists, overlapping fingers, rocker-bottom feet |
| Patau (T13) | Trisomy 13 | Holoprosencephaly, cleft lip/palate, polydactyly |
| DiGeorge | 22q11 deletion | Conotruncal defects, thymic aplasia, hypocalcemia, cleft palate |
| Angelman | Loss of maternal UBE3A | Ataxia, seizures, inappropriate laughter |
| Prader–Willi | Loss of paternal 15q expression | Infant hypotonia → childhood hyperphagia/obesity, hypogonadism |
| Turner | 45,X | Webbed neck, coarctation, streak ovaries |
Test-Day Thinking: A Quick Algorithm
When you see a genetics vignette in a newborn, ask:
- Is there a signature “one-liner” clue?
- Cat-like cry → Cri du chat
- Conotruncal + hypocalcemia → DiGeorge
- Polydactyly + holoprosencephaly → Patau
- Is it likely a microdeletion vs trisomy vs single-gene?
- Microdeletion syndromes often need FISH/microarray
- Trisomies often present with multiple congenital anomalies + characteristic limbs/facies
- Does the course change over time?
- Prader–Willi: hypotonia early → hyperphagia later
- Fragile X: features emerge with development
Take-Home Points (What to Remember Under Pressure)
- Cri du chat =
- The cry is the clue: high-pitched, cat-like, neonatal.
- If the answer choices include several syndromes with developmental delay, anchor on the most specific feature (cry, limb posture, immune findings, midline defects).
- Microdeletion? Think FISH or chromosomal microarray.