Rare Disease Conditions Eligibility Criteria 100,000 Genomes Project Document Key: PAR-GUI-058 Version: 1.9.0 Function Participants Version 1.9.0 Document Key PAR-GUI-058 Document Owner Richard Scott Clinical Lead for Review Date 20/10/19 Rare Disease Document Authors and Job Andrew Head of Data Status Draft ☐ Titles Devereau Models Live ☒ Archive Richard Scott Clinical Lead for ☐ Rare Disease Ellen Thomas Clinical Lead for NHS Genomic Medicine Document Reviewer and Richard Scott Clinical Lead for Effective Date 20/04/18 Job Title Rare Disease Document Approvers and Richard Scott Clinical Lead for Rare Disease Job Titles Tom Fowler Deputy Chief Scientist Electronic Signature Date Approved Transaction Number Rare Disease Conditions Eligibility Criteria: Document Key PAR-GUI-058 Version Number 1.9.0 This document is uncontrolled if printed Page 1 of 326 Contents 1. Document Version History ................................................................................................................................................. 3 2. Purpose of this document .................................................................................................................................................. 3 3. Summary of Changes .......................................................................................................................................................... 4 4. Structure and background to eligibility statements .......................................................................................................... 6 5. Rare Disease Conditions Eligibility Criteria ........................................................................................................................ 7 Cardiovascular disorders (10950) ........................................................................................................................................ 7 Ciliopathies (10963) ........................................................................................................................................................... 43 Dermatological disorders (10956) ..................................................................................................................................... 50 Dysmorphic and congenital abnormality syndromes (10959) ........................................................................................... 66 Endocrine disorders (10967) ........................................................................................................................................... 100 Gastroenterological disorders (38581) ............................................................................................................................ 120 Growth disorders (10974) ............................................................................................................................................... 128 Haematological and immunological disorders (10977) ................................................................................................... 137 Hearing and ear disorders (10980) .................................................................................................................................. 146 Infectious diseases (42209) ............................................................................................................................................. 155 Metabolic disorders (10983) ........................................................................................................................................... 157 Neurology and neurodevelopmental disorders (10988) ................................................................................................. 168 Ophthalmological disorders (10996) ............................................................................................................................... 217 Psychiatric disorders (71735) .......................................................................................................................................... 233 Renal and urinary tract disorders (11000) ....................................................................................................................... 237 Respiratory disorders (33353) ......................................................................................................................................... 254 Rheumatological disorders (11009) ................................................................................................................................. 260 Skeletal disorders (11005) ............................................................................................................................................... 266 Tumour syndromes (11012) ............................................................................................................................................ 277 Ultra-rare disorders (30783) ............................................................................................................................................ 298 Genomic medicine service indications (82157) ............................................................................................................... 304 Rare Disease Conditions Eligibility Criteria: Document Key PAR-GUI-058 Version Number 1.9.0 This document is uncontrolled if printed Page 2 of 326 1. Document Version History Version Author Date Summary of main changes and reasons approved 1.9.0 Andrew April 2018 Final Version Devereau 2. Purpose of this document The aim of this document is to provide an up-to-date list of eligibility criteria for conditions approved for recruitment within the Genomics England Rare Diseases Programme. Rare Disease Conditions Eligibility Criteria: Document Key PAR-GUI-058 Version Number 1.9.0 This document is uncontrolled if printed Page 3 of 326 3. Summary of Changes The follow table summarises the changes in Rare Disease version 1.9. Only additions have been made to the catalogue: two new diseases have been added to the existing Categories, and a new Category – ‘Genomic Medicine Service Indications’ – has been added containing a new subcategory ‘Whole Genome Sequencing Indications’ and 22 new diseases. These new items are highlighted in yellow. The Genomic Medicine Service Indications will be available as first line tests in the new NHS Genomic Medicine Service. Prior to that, local clinical teams can use them as a first line test or in parallel to, or following, current diagnostic testing according to the clinical setting, noting that the 100,000 Genomes Project pipeline does not yet report on all variant types that will be available in the NHS pipeline and is not accredited. Other tests that should be considered are listed in the ‘Where in pathway’ section of the Inclusion criteria. Category Subcategory Disease Motor and Sensory Motor and sensory Pain channelopathies (82148) Disorders of the PNS disorders of the (10991) PNS (10991) Renal and urinary Syndromes with Familial IgA nephropathy and IgA vasculitis (82147) tract disorders prominent renal (11000) abnormalities (11001) Genomic medicine Whole genome GMS R14 Acutely unwell infants with a likely service indications sequencing monogenic disorder (82160) (82157) indications (82159) GMS R27 Congenital malformation and dysmorphism syndromes - likely monogenic (82161) GMS R69 Floppy infant with a likely central cause (82162) GMS R29 Moderate, severe or profound intellectual disability (82163) GMS R89 Ultra-rare and atypical monogenic disorders (82164) GMS R100 Rare syndromic craniosynostosis or isolated multisuture synostosis (82165) Rare Disease Conditions Eligibility Criteria: Document Key PAR-GUI-058 Version Number 1.9.0 This document is uncontrolled if printed Page 4 of 326 GMS R104 Skeletal dysplasia (82166) GMS R143 Neonatal diabetes (82167) GMS R98 Likely inborn error of metabolism - targeted testing not possible (82168) GMS R83 Arthrogryposis (82185) GMS R84 Cerebellar anomalies (82169) GMS R87 Cerebral malformation (82170) GMS R61 Childhood onset hereditary spastic paraplegia (82171) GMS R109 Childhood onset leukodystrophy (82172) GMS R59 Early onset or syndromic epilepsy (82173) GMS R54 Hereditary ataxia with onset in adulthood (82174) GMS R55 Hereditary ataxia with onset in childhood (82175) GMS R85 Holoprosencephaly - NOT chromosomal (82176) GMS R86 Hydrocephalus (82177) GMS R381 Other rare neuromuscular disorders (82178) GMS R88 Severe microcephaly (82179) GMS R193 Cystic renal disease (82180) Rare Disease Conditions Eligibility Criteria: Document Key PAR-GUI-058 Version Number 1.9.0 This document is uncontrolled if printed Page 5 of 326 4. Structure and background to eligibility statements For each disease listed we provide an “eligibility statement” composed of the following key information: 1. Inclusion criteria – the clinical features, characteristics or investigations that probands with a given disease must have in order to be eligible for recruitment. 2. Exclusion criteria - the clinical features, characteristics or investigation findings that participants with a given disease must not have in order to be eligible for recruitment. 3. Prior genetic testing – this sets out both in general terms, and where appropriate more specifically, the genetic testing which participants with a given disease must have performed prior to recruitment. Each eligibility statement has been informed by at least one clinician specialising in the field and incorporates comments provided during the consultation period