TY - JOUR
T1 - Jansen-de Vries syndrome : expansion of the PPM1D clinical and phenotypic spectrum in 34 families
AU - Wojcik, M.H.
AU - Srivastava, S.
AU - Agrawal, P.B.
AU - Balci, T.B.
AU - Callewaert, B.
AU - Calvo, P.L.
AU - Carli, D.
AU - Caudle, M.
AU - Colaiacovo, S.
AU - Cross, L.
AU - Demetriou, K.
AU - Drazba, K.
AU - Dutra-Clarke, M.
AU - Edwards, Matthew
AU - Genetti, C.A.
AU - Grange, D.K.
AU - Hickey, S.E.
AU - Isidor, B.
AU - Küry, S.
AU - Lachman, H.M.
AU - Lavillaureix, A.
AU - Lyons, M.J.
AU - Marcelis, C.
AU - Marco, E.J.
AU - Martinez-Agosto, J.A.
AU - Nowak, C.
AU - Pizzol, A.
AU - Planes, M.
AU - Prijoles, E.J.
AU - Riberi, E.
AU - Rush, E.T.
AU - Russell, B.E.
AU - Sachdev, R.
AU - Schmalz, B.
AU - Shears, D.
AU - Stevenson, D.A.
AU - Wilson, K.
AU - Jansen, S.
AU - de, Vries
AU - Curry, C.J.
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
KW - cyclic vomiting
KW - hypersocial personality
KW - developmental delay
KW - Jansen-de Vries syndrome
KW - PPM1D
UR - https://hdl.handle.net/1959.7/uws:73851
UR - http://www.scopus.com/inward/record.url?scp=85159181090&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.63226
DO - 10.1002/ajmg.a.63226
M3 - Article
SN - 1552-4825
VL - 191
SP - 1900
EP - 1910
JO - American Journal of Medical Genetics. Part A
JF - American Journal of Medical Genetics. Part A
IS - 7
ER -