International meeting on Wolf‐Hirschhorn syndrome: Update on the nosology and new insights on the pathogenic mechanisms for seizures and growth delay

“An International Meeting on Wolf‐Hirschhorn Syndrome (WHS)” was held at The University Hospital La Paz in Madrid, Spain (October 13–14, 2017). One hundred and twenty‐five people, including physicians, scientists and affected families, attended the meeting. Parent and patient advocates from the Spanish Association of WHS opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes. These proceedings will review the major points of discussion.

[1]  Guanghai Wang,et al.  De novo truncating variant in NSD2gene leading to atypical Wolf-Hirschhorn syndrome phenotype , 2019, BMC Medical Genetics.

[2]  A. Avendaño,et al.  [Wolf-Hirschhorn syndrome. Description of five cases characterized by means of single nucleotide polymorphism microarrays]. , 2019, Archivos argentinos de pediatria.

[3]  E. Zmuda,et al.  De novo loss-of-function variants in NSD2 (WHSC1) associate with a subset of Wolf–Hirschhorn syndrome , 2019, Cold Spring Harbor molecular case studies.

[4]  E. Thorland,et al.  Developmental delay and failure to thrive associated with a loss‐of‐function variant in WHSC1 (NSD2) , 2018, American journal of medical genetics. Part A.

[5]  A. Battaglia,et al.  Risk of hepatic neoplasms in Wolf–Hirschhorn syndrome (4p‐): Four new cases and review of the literature , 2018, American journal of medical genetics. Part A.

[6]  H. Houlden,et al.  LETM1 couples mitochondrial DNA metabolism and nutrient preference , 2018, EMBO molecular medicine.

[7]  F. Alkuraya,et al.  De novo truncating variants in WHSC1 recapitulate the Wolf–Hirschhorn (4p16.3 microdeletion) syndrome phenotype , 2018, Genetics in Medicine.

[8]  M. Zollino,et al.  Dissecting the Wolf–Hirschhorn syndrome phenotype: WHSC1 is a neurodevelopmental gene contributing to growth delay, intellectual disability, and to the facial dysmorphism , 2018, Journal of Human Genetics.

[9]  I. Kanivets,et al.  De novo nonsense mutation in WHSC1 (NSD2) in patient with intellectual disability and dysmorphic features , 2018, Journal of Human Genetics.

[10]  A. Battaglia,et al.  A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf–Hirschhorn syndrome , 2018, Epilepsy & Behavior.

[11]  M. F. Galera,et al.  Cytogenomic Integrative Network Analysis of the Critical Region Associated with Wolf-Hirschhorn Syndrome , 2018, BioMed research international.

[12]  Pedro P. Rocha,et al.  Wolf-Hirschhorn Syndrome Candidate 1 Is Necessary for Correct Hematopoietic and B Cell Development. , 2017, Cell reports.

[13]  P. Lapunzina,et al.  [Wolf-Hirschhorn syndrome. Description of a Spanish cohort of 51 cases and a literature review]. , 2017, Revista de neurología (Ed. impresa).

[14]  E. Wassman,et al.  A case for cannabidiol in Wolf–Hirschhorn syndrome seizure management , 2016, American journal of medical genetics. Part A.

[15]  P. Lapunzina,et al.  Síndrome de Wolf-Hirschhorn. Descripción de una cohorte española de 51 casos y revisión de la bibliografía , 2017 .

[16]  A. Shilatifard,et al.  Epigenetics of hematopoiesis and hematological malignancies , 2016, Genes & development.

[17]  Colin A. Johnson,et al.  Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia. , 2016, American journal of human genetics.

[18]  A. Battaglia,et al.  Chromosomal microarray testing identifies a 4p terminal region associated with seizures in Wolf–Hirschhorn syndrome , 2016, Journal of Medical Genetics.

[19]  Sarah T South,et al.  Wolf–Hirschhorn syndrome: A review and update , 2015, American journal of medical genetics. Part C, Seminars in medical genetics.

[20]  L. Ostacoli,et al.  Emotional Burden and Coping Strategies of Parents of Children with Rare Diseases , 2015 .

[21]  M. Resende,et al.  Is functional dependence of Duchenne muscular dystrophy patients determinant of the quality of life and burden of their caregivers? , 2015, Arquivos de neuro-psiquiatria.

[22]  R. Pfundt,et al.  Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf‐Hirschhorn syndrome–associated seizures disorder , 2014, Epilepsia.

[23]  J. Vermeesch,et al.  LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition , 2014, Disease Models & Mechanisms.

[24]  A. Battaglia,et al.  Confirmation of chromosomal microarray as a first-tier clinical diagnostic test for individuals with developmental delay, intellectual disability, autism spectrum disorders and dysmorphic features. , 2013, European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society.

[25]  S. Newman,et al.  Systematic review of the effects of telecare provided for a person with social care needs on outcomes for their informal carers. , 2013, Health & social care in the community.

[26]  J. García-Peñas,et al.  [Wolf-Hirschhorn syndrome. A series of 27 patients: their epidemiological and clinical characteristics. The current situation of the patients and the opinions of their caregivers regarding the diagnostic process]. , 2013, Revista de neurología (Ed. impresa).

[27]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[28]  D. Cameron,et al.  Reported Sensory Processing of Children with Down Syndrome , 2010, Physical & occupational therapy in pediatrics.

[29]  Hiromi Hirata,et al.  Biogenesis of GPI-anchored proteins is essential for surface expression of sodium channels in zebrafish Rohon-Beard neurons to respond to mechanosensory stimulation , 2010, Development.

[30]  Leslie G Biesecker,et al.  Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. , 2010, American journal of human genetics.

[31]  Daniel J Goble,et al.  Deficits in the ability to use proprioceptive feedback in children with hemiplegic cerebral palsy , 2009, International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation.

[32]  A. Battaglia,et al.  Spectrum of epilepsy and electroencephalogram patterns in Wolf–Hirschhorn syndrome: experience with 87 patients , 2009, Developmental medicine and child neurology.

[33]  K. Hirschhorn.  A short history of the initial discovery of the Wolf–Hirschhorn syndrome , 2008, American journal of medical genetics. Part C, Seminars in medical genetics.

[34]  G. Neri,et al.  On the nosology and pathogenesis of Wolf–Hirschhorn syndrome: Genotype–phenotype correlation analysis of 80 patients and literature review , 2008, American journal of medical genetics. Part C, Seminars in medical genetics.

[35]  H. Tager-Flusberg,et al.  Sensory clusters of toddlers with autism spectrum disorders: differences in affective symptoms. , 2008, Journal of child psychology and psychiatry, and allied disciplines.

[36]  A. Battaglia,et al.  Comprehensive analysis of Wolf–Hirschhorn syndrome using array CGH indicates a high prevalence of translocations , 2008, European Journal of Human Genetics.

[37]  A. M. van der Bliek,et al.  Inverse correlation between expression of the Wolfs Hirschhorn candidate gene Letm1 and mitochondrial volume in C. elegans and in mammalian cells. , 2007, Human molecular genetics.

[38]  H. Fiegler,et al.  Guidelines for molecular karyotyping in constitutional genetic diagnosis , 2007, European Journal of Human Genetics.

[39]  S. van Vooren,et al.  The t(4;8) is mediated by homologous recombination between olfactory receptor gene clusters, but other 4p16 translocations occur at random. , 2007, Genetic counseling.

[40]  G. Neri,et al.  Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2. , 2003, American journal of human genetics.

[41]  H. Dörr,et al.  First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation. , 2001, American journal of medical genetics.

[42]  M. Altherr,et al.  Comparative analysis of a novel gene from the Wolf-Hirschhorn/Pitt-Rogers-Danks syndrome critical region. , 1999, Genomics.

[43]  A. Moorman,et al.  WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma. , 1998, Human molecular genetics.

[44]  E. Zackai,et al.  A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region. , 1997, Human molecular genetics.

[45]  M. Elliott,et al.  Health and social care in the community. , 1989, Elderly care.

[46]  A. Ayres.  Interrelation of Perception, Function, and Treatment , 1966 .

[47]  Ayres Aj.  TACTILE FUNCTIONS. THEIR RELATION TO HYPERACTIVE AND PERCEPTUAL MOTOR BEHAVIOR , 1964 .

[48]  A. Ayres.  TACTILE FUNCTIONS. THEIR RELATION TO HYPERACTIVE AND PERCEPTUAL MOTOR BEHAVIOR. , 1964, The American journal of occupational therapy : official publication of the American Occupational Therapy Association.