Jansen-de Vries syndrome: Expansion of the PPM1D clinical and phenotypic spectrum in 34 families.

Document Type

Article

Publication Date

7-2023

Identifier

DOI: 10.1002/ajmg.a.63226

Abstract

Jansen-de Vries syndrome (JdVS) is a neurodevelopmental condition attributed to pathogenic variants in Exons 5 and 6 of PPM1D. As the full phenotypic spectrum and natural history remain to be defined, we describe a large cohort of children and adults with JdVS. This is a retrospective cohort study of 37 individuals from 34 families with disease-causing variants in PPM1D leading to JdVS. Clinical data were provided by treating physicians and/or families. Of the 37 individuals, 27 were male and 10 female, with median age 8.75 years (range 8 months to 62 years). Four families document autosomal dominant transmission, and 32/34 probands were diagnosed via exome sequencing. The facial gestalt, including a broad forehead and broad mouth with a thin and tented upper lip, was most recognizable between 18 and 48 months of age. Common manifestations included global developmental delay (35/36, 97%), hypotonia (25/34, 74%), short stature (14/33, 42%), constipation (22/31, 71%), and cyclic vomiting (6/35, 17%). Distinctive personality traits include a hypersocial affect (21/31, 68%) and moderate-to-severe anxiety (18/28, 64%). In conclusion, JdVS is a clinically recognizable neurodevelopmental syndrome with a characteristic personality and distinctive facial features. The association of pathogenic variants in PPM1D with cyclic vomiting bears not only medical attention but also further pathogenic and mechanistic evaluation.

Journal Title

American journal of medical genetics. Part A

Volume

191

Issue

7

First Page

1900

Last Page

1910

MeSH Keywords

Adult; Child; Female; Humans; Infant; Male; Developmental Disabilities; Intellectual Disability; Neurodevelopmental Disorders; Phenotype; Protein Phosphatase 2C; Retrospective Studies; Vomiting; Child, Preschool; Adolescent; Young Adult; Middle Aged

Keywords

Jansen-de Vries syndrome; PPM1D; cyclic vomiting; developmental delay; hypersocial personality

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