Jansen de Vries syndrome: Report of four new patients and review of the literature.

Jansen de Vries syndrome (JDVS, OMIM: 617450) is a rare neurodevelopmental disorder associated with hypotonia, behavioral features, high threshold to pain, short stature, ophthalmological abnormalities, dysmorphism and occasionally a structural cardiac condition. It is caused by truncating variants of the last and penultimate exons of PPM1D. So far, 21 patients with JVDS have been reported in the literature. Here, we describe four novel cases of JVDS and review the current literature. Notably, our patients 1, 3 and 4 do not have intellectual disability albeit they have significant developmental difficulties. Thus, the phenotype may span from a classic intellectual disability syndrome to a milder neurodevelopmental disorder. Interestingly, two of our patients have received successful growth hormone treatment. Considering the phenotype of all the known JDVS patients, a cardiological consultation is recommended, as at least 7/25 patients showed a structural cardiac defect. Episodic fever and vomiting may associate with hypoglycemia and may even mimic a metabolic disorder. We also report the first JDVS patient with a mosaic gene defect and a mild neurodevelopmental phenotype. • Truncating variants of the penultimate and last exons of PPM1D cause Jansen de Vries syndrome. • The phenotype varies from intellectual disability to milder cognitive impairment. • Some patients with Jansen de Vries syndrome may benefit from growth hormone therapy. • A cardiology consultation would be beneficial for children with this condition. • Jansen de Vries syndrome may mimic a metabolic disorder. [ABSTRACT FROM AUTHOR]