Discussion

Koolen-de Vries syndrome (MIM#610443) is a rare microdeletion syndrome involving the 17q21.31 region, which was first described by Koolen and de Vries in 2006.  Its incidence has been estimated at 1:16,000 in the general population [1]. This syndrome is characterised by developmental delay, intellectual disability, hypotonia, epilepsy, characteristic facial features, and congenital malformations in multiple organ systems [2].

Fetuses with Koolen-de Vries syndrome may present with the following:

• Intrauterine growth retardation (26%)
• Central nervous system defects (53%) including corpus callosum hypoplasia/aplasia, enlarged ventricles, hydrocephalus, and heterotopias
• Facial dysmorphism (80%)
• Cardiac abnormalities (39%) including atrial septal defect, ventricular septal defect, hypoplastic aortic valve, bicuspid aortic valve, common left pulmonary vein, dysplastic pulmonary valve, dilated left ventricle, or anomalous right subclavian artery
• Urogenital anomalies (45%)  [3]

Developmental delay, behavioral problems and intellectual disability cause postnatal disability.  It was reported that all individuals with Koolen-de Vries syndrome have developmental delay and intellectual disability. The level of intellectual disability was mild in 42%, moderate in 37% and severe in 22% [3].

References

[1] Koolen DA, Kramer JM, Kornelia Neveling K,et al. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nat Genet. 2012 Apr 29;44(6):639-41.
[2] Shaw-Smith C, Pittman AM, Willatt L et al. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Nat Genet 2006; 38: 1032–1037.
[3] Koolen DA, Pfundt R, Linda K, et al. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant. Eur J Hum Genet. 2016 May;24(5):652-9.