All congenital structural defects in the body are the result of an error in morphogenesis. Morphogenesis takes place around 25 to 29 days of intrauterine life. Chromosomal syndromes involve a phenotypically significant structural and/or numerical chromosomal abnormality.An insufficient function of the velopharyngeal sphincter induces excessive nasal resonance during speech. This abnormal resonance is called hypernasality. A deficient seal of the velopharyngeal sphincter creates an airflow leaking into the rhinopharynx, resulting in abnormal air turbulence through the nasal cavities which can be easily perceived and is called nasal emission. Hypernasality and nasal emission are the clinical signs of velopharyngeal insufficiency (VPI). In other words, VPI is the velopharyngeal inability to create an efficient seal during speech.Most chromosomal syndromes cause VPI as a consequence of a cleft palate. However, when patients with a chromosomal abnormality and VPI are being clinically assessed, it is essential to keep in mind that an apparently and morphologically intact uvula and velum do not rule out the possibility of a sub mucous cleft palate.Several chromosomal syndromes can be associated with VPI, including: 22q11.2 deletion syndrome (22q11.2DS) or velocardiofacial syndrome among other names, Opitz G/BBB syndrome (OS), Kabuki syndrome (KS) and Jacobsen syndrome (JS). Pierre -Robin sequence (PRS) can be associated with some chromosomal syndromes. In these cases, PRS is referred as syndromic PRS.In this paper, the diagnosis and management of VPI in the most common chromosomal syndromes is discussed.