A 3-year-old girl presents to the pediatric clinic with developmental delay, severe speech impairment, and a history of a distinctive high-pitched cry in infancy that has now resolved. On examination, she has microcephaly, round facies, widely spaced eyes, and low-set ears. Her karyotype is shown in the diagram. The structure marked **A** represents the chromosomal abnormality responsible for her clinical presentation. Which of the following is the MOST characteristic clinical feature that would have been noted in the neonatal period due to this deletion?

Explanation

## Why "High-pitched cat-like cry resulting from laryngeal and nervous system abnormalities" is right The deletion of the short arm of chromosome 5 (marked **A**) causes cri-du-chat syndrome (5p− deletion syndrome). The pathognomonic neonatal finding is the high-pitched, cat-like cry—a KEY characteristic feature that results from laryngeal abnormalities combined with nervous system involvement. This distinctive cry typically resolves by age 2 years, making it the most clinically recognizable early sign of this deletion syndrome. The patient's history of this cry in infancy, now resolved at age 3, is classic for cri-du-chat syndrome (Harrison 21e Ch 471). ## Why each distractor is wrong - **Severe hypercalcemia requiring urgent medical intervention**: This is characteristic of Williams syndrome (7q11.23 deletion), not cri-du-chat. Infantile hypercalcemia is a hallmark of Williams syndrome, not 5p− deletion. - **Congenital heart defect with interrupted aortic arch type B**: Interrupted aortic arch type B is a classic cardiac defect of 22q11.2 deletion (DiGeorge/velocardiofacial syndrome), not cri-du-chat. While ~30% of cri-du-chat patients may have cardiac defects, interrupted aortic arch is not typical. - **Hypotonia with severe feeding difficulty and failure to thrive**: While hypotonia and growth retardation do occur in cri-du-chat, severe feeding difficulty and failure to thrive are more characteristic of Prader-Willi syndrome (15q11-13 paternal deletion), which presents with profound neonatal hypotonia and feeding problems. **High-Yield:** The distinctive high-pitched cat-like cry in a neonate with dysmorphic facies (round face, hypertelorism, low-set ears) and developmental delay is pathognomonic for cri-du-chat syndrome (5p− deletion); the cry typically resolves by age 2 years, but the intellectual disability and speech delay persist. [cite: Harrison 21e Ch 471]