A 2-month-old male infant born to non-consanguineous parents presents with a high-pitched, monochromatic, feline-like cry, severe hypotonia, microcephaly, and widely spaced eyes. Karyotype analysis is performed. The structure marked **A** in the diagram shows a terminal deletion of the short arm of chromosome 5. Which of the following clinical features is MOST PATHOGNOMONIC for the chromosomal abnormality represented by this deletion and typically prompts initial diagnostic suspicion in the neonatal period?

Explanation

## Why "High-pitched, cat-like cry that characteristically fades by age 2 years" is right The pathognomonic clinical feature of cri-du-chat syndrome (5p- deletion) is the distinctive high-pitched, monochromatic, plaintive feline-like cry caused by abnormal laryngeal and epiglottic development. This cry is the hallmark finding that typically prompts initial diagnostic suspicion in the neonatal period and gives the syndrome its name ("cry of the cat"). Critically, this cry characteristically fades by age 2 years, making it a time-limited but highly specific diagnostic clue. The deletion marked **A** (terminal deletion of 5p15.2-15.3) disrupts genes including TERT and SEMA5A, leading to this pathognomonic laryngeal phenotype. This feature is the KEY finding that distinguishes cri-du-chat from other chromosomal deletion syndromes and is the primary reason for early diagnostic suspicion and karyotype ordering. ## Why each distractor is wrong - **Severe intellectual disability with IQ typically <50 in most affected individuals**: While severe intellectual disability is indeed a cardinal feature of cri-du-chat syndrome, it is NOT pathognomonic—it occurs in many chromosomal and genetic syndromes (Down syndrome, Edwards syndrome, Patau syndrome, etc.). It does not prompt initial diagnostic suspicion in the neonatal period and is not the distinguishing feature. - **Microcephaly with hypertelorism and downslanting palpebral fissures**: Although these craniofacial features are characteristic of cri-du-chat, they are not pathognomonic. Microcephaly and hypertelorism occur in multiple syndromes. The downslanting palpebral fissures (contrasting with upslanting in Down syndrome) are helpful but not specific enough to prompt immediate diagnostic suspicion without the cry. - **Cardiac defects present in approximately 30% of cases, including VSD and PDA**: Cardiac defects occur in only ~30% of cri-du-chat cases and are not pathognomonic—they are common in many chromosomal syndromes. They are neither sensitive nor specific for this diagnosis. **High-Yield:** The pathognomonic "cat-like cry" of cri-du-chat is the KEY neonatal finding that fades by age 2—it is the diagnostic clue that triggers karyotype testing and distinguishes this 5p- deletion from other chromosomal syndromes. [cite: Nelson Pediatrics 21e Ch 98; Smith's Recognizable Patterns 7e]