Published Studies and Papers
This ultra-rare disorder, caused by variations on the HNRNPH2 gene, was first identified by Drs. Jennifer Bain and Wendy Chung, who published the first paper on the disorder in the American Journal of Human Genetics in September 2016.
View the full study here: “Variants in HNRNPH2 on the X chromosome are associated with a neurodevelopmental disorder in females”
Subsequent papers have been published as a result of evaluations conducted during the annual family meetings, as part of the critical Natural History Study.
Below is a summary of the most recent publication by Dr. Jennifer Bain and her team conducting the Natural History Study:
Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder
Jennifer M. Bain, MD, PhD, Olivia Thornburg, BA, Cheryl Pan, Donnielle Rome-Martin, MS, OTR/L, ATR, Lia Boyle, BA, Xiao Fan, PhD, Orrin Devinsky, MD, Richard Frye, MD, PhD, Silke Hamp, MD, Cynthia G. Keator, MD, Nicole M. LaMarca, DNP, Alexis B.R. Maddocks, MD, Marcos Madruga-Garrido, MD, Karen Y. Niederhoffer, MD, Francesca Novara, PhD, Angela Peron, MD, Elizabeth Poole-Di Salvo, MD, MPH, Rachel Salazar, DPT, Steven A. Skinner, MD, Gabriela Soares, MD, Sylvie Goldman, PhD, and Wendy K. Chung, MD, PhD
To expand the clinical phenotype of the X-linked HNRNPH2-related neurodevelopmental disorder in 33 individuals.
Participants were diagnosed with pathogenic or likely pathogenic variants in HNRNPH2 using American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria, largely identified via clinical exome sequencing. Genetic reports were reviewed. Clinical data were collected by retrospective chart review and caregiver report including standardized parent report measures.
We expand our clinical characterization of HNRNPH2-related disorders to include 33 individuals, aged 2–38 years, both females and males, with 11 different de novo missense variants, most within the nuclear localization signal. The major features of the phenotype include developmental delay/intellectual disability, severe language impairment, motor problems, growth, and musculoskeletal disturbances. Minor features include dysmorphic features, epilepsy, neuropsychiatric diagnoses such as autism spectrum disorder, and cortical visual impairment. Although rare, we report early stroke and premature death with this condition.
The spectrum of X-linked HNRNPH2-related disorders continues to expand as the allelic spectrum and identification of affected males increases.
Other researchers have published studies to expand on Dr. Bain's original publication in 2016 identifying HNRNPH2 genetic variations as pathogenic. Click on the title below to read the full study.
Bain type of X-linked syndromic mental retardation in a male with a pathogenic variant in HNRNPH2. This study reports on two siblings, one male and one female, born to a consanguineous couple in India.