Rare (Jan 2024)
An expansion of the phenotype in individuals with SYNCRIP-Related Neurodevelopmental Disorder
- Tooba Shafiq,
- Joanna L. Feng,
- Lindsay Phillips,
- Kara Murias,
- Marcia Ferguson,
- Kristin Baranano,
- Alaina Acchione,
- Patricia Kipkemoi,
- Collins Kipkoech,
- Eunice Chepkemoi,
- Amina Abubakar,
- Charles Newton,
- Celia van der Merwe,
- Emily O’Heir,
- Alice Galvin,
- Aixa Gonzalez Garcia,
- Alisha D’Souza,
- Jennifer Stefanich,
- Amelle Shillington,
- Annabelle Tuttle,
- Erin Torti,
- Elen Zhu,
- Margaretha AJ Morsink,
- Ekaterina Lebayle,
- Barbara Corneo,
- Christopher L. Ricupero,
- Ping Yee Billie Au,
- Antonie D. Kline,
- Meena Balasubramanian,
- Jennifer Bain,
- Madelyn A. Gillentine
Affiliations
- Tooba Shafiq
- SUNY Downstate Health Sciences University, Brooklyn, NY, USA
- Joanna L. Feng
- Columbia University Irving Medical Center, Department of Neurology, Division of Child Neurology, New York, NY, USA
- Lindsay Phillips
- Alberta Children's Hospital Research Institute, University of Calgary, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Kara Murias
- Alberta Children's Hospital Research Institute, University of Calgary, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Marcia Ferguson
- Harvey Institute for Human Genetics, Greater Baltimore Medical Center, Baltimore, MD, USA
- Kristin Baranano
- Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA
- Alaina Acchione
- Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA
- Patricia Kipkemoi
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Collins Kipkoech
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Eunice Chepkemoi
- KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya
- Amina Abubakar
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Charles Newton
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Celia van der Merwe
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Emily O’Heir
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Alice Galvin
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Aixa Gonzalez Garcia
- Department of Pediatrics, University of Arkansas for Medical Sciences, Fayetteville, AR, USA
- Alisha D’Souza
- Department of Pediatrics, University of Arkansas for Medical Sciences, Fayetteville, AR, USA
- Jennifer Stefanich
- Akron Children’s Genetic Center, Akron, OH, USA
- Amelle Shillington
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Annabelle Tuttle
- GeneDx, Gaithersburg, MD, USA
- Erin Torti
- GeneDx, Gaithersburg, MD, USA
- Elen Zhu
- Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, New York, NY, USA
- Margaretha AJ Morsink
- Department of Biomedical Engineering, Columbia University, New York, NY, USA
- Ekaterina Lebayle
- Columbia Stem Cell Initiative Stem Cell Core, Columbia University Irving Medical Center, New York, NY, USA
- Barbara Corneo
- Columbia Stem Cell Initiative Stem Cell Core, Columbia University Irving Medical Center, New York, NY, USA
- Christopher L. Ricupero
- Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, New York, NY, USA
- Ping Yee Billie Au
- Alberta Children's Hospital Research Institute, University of Calgary, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Antonie D. Kline
- Harvey Institute for Human Genetics, Greater Baltimore Medical Center, Baltimore, MD, USA
- Meena Balasubramanian
- Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK; Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK
- Jennifer Bain
- Columbia University Irving Medical Center, Department of Neurology, Division of Child Neurology, New York, NY, USA; New York Presbyterian, Morgan Stanley Children’s Hospital, New York, USA
- Madelyn A. Gillentine
- HNRNP Family Foundation, Seattle, WA, USA; Correspondence to: 1570 W. Armory Way, #194, Seattle, WA, USA.
- Journal volume & issue
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Vol. 2
p. 100052
Abstract
Disruption of genes within the HNRNP gene family has been observed in neurodevelopmental and neurodegenerative diseases. The HNRNP-Related Neurodevelopmental Disorders (HNRNP-RNDDs), while each unique, have been recently described with similar clinical and molecular features across variation in several genes. However, the phenotypic information on these patients is still lacking. In this case series we aim to describe the phenotypes that are associated with SYNCRIP-Related Neurodevelopmental Disorder (SYNCRIP-RNDD). We describe in depth ten novel individuals and one previously published individual with mostly de novo and predicted damaging variants in SYNCRIP, consistent with a diagnosis of SYNCRIP-RNDD. We also describe previously published patients, many of which are from large cohort studies, as well as individuals from patient databases. Here, we expand the phenotype of SYNCRIP-RNDD beyond a generic neurodevelopmental disorder to a variable syndrome consisting of mild to borderline developmental delay/intellectual disability, speech and language delay, behavioral differences such as autism spectrum disorder, structural brain anomalies, hypotonia, and seizures. Inconsistent dysmorphic features were also observed, with the few recurrent findings including long eyelashes, mildly deep-set eyes, prominent ears, and thin or thick lips. This study increases our understanding of SYNCRIP-RNDD, as well as HNRNP-RNDDs broadly.
