Prader-Willi syndrome results from loss of paternal 15q11-q13. When the same region is deleted from the maternal chromosome, which syndrome results?

• A Angelman syndrome (severe intellectual disability, ataxia, seizures, happy puppet syndrome) ✓
• B Fragile X syndrome (macroorchidism, intellectual disability, autism)
• C Beckwith-Wiedemann syndrome (overgrowth, macroglossia, hypoglycaemia)
• D Russell-Silver syndrome (growth restriction, asymmetry, IQ normal)

Explanation

The 15q11-q13 region contains imprinted genes expressed exclusively from either the paternal or maternal allele. Deletion of paternal 15q11-q13 (or maternal uniparental disomy of chromosome 15) causes Prader-Willi syndrome (hypotonia, hyperphagia, obesity, hypogonadism). Deletion of maternal 15q11-q13 (or paternal UPD15) causes Angelman syndrome, because the critical maternally expressed gene is UBE3A (encoding a ubiquitin ligase essential for neurodevelopment). Angelman features include severe intellectual disability, absent speech, ataxic gait, seizures, and inappropriate happy affect. Fragile X results from FMR1 CGG expansion; Beckwith-Wiedemann involves IGF2/H19 imprinting on chromosome 11p.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.