Oxford Congenital Myasthenia Service referrals

The Oxford Congenital Myasthenia Service is a national referral centre for children and adults in whom a Congenital Myasthenic Syndrome (CMS) is suspected.

These clinically diverse inherited disorders can arise from mutations in a number of different genes (see below).

The service is funded by the National Commissioning Group (NCG, formerly the National Specialist Commissioning Advisory Group), as part of the Diagnostic and Advisory Service for Rare Neuromuscular Disorders.

Oxford University Hospitals' Neuromuscular Services have been recognised as a European Rare Neuromuscular Centre.

Diagnosis and management advice

These depend on a combined approach incorporating:

clinical assessment
specialised electromyography
analysis of DNA/genetic testing
analysis of serum antibodies (including live CBA)
outpatient or inpatient evaluation of specific therapies.

Gene screening

Currently we are able to screen for mutations in the following ways.

1. National Genomic Test Directory (NGTD) R80 Gene Panel: List of 27 genes included in the targeted R80v5.0 Congenital Myasthenic Syndrome panel. Read depth coverage (% at 20X) is held by the laboratory and can be obtained if required.

AGRN	COL13A1	PLEC
ALG2	COLQ	RAPSN
ALG14	DOK7	SCN4A
CHAT	DPAGT1	SLC18A3
CHRNA1	GFPT1	SLC25A1
CHRNB1	GMPPB	SLC5A7
CHRND	LRP4	STT2
CHRNE	MUSK	TOR1AIP1
CHRNG	MYO9A	VAMP1

CHRNA, CHRNB, CHRND and CHRNE - the genes encoding the muscle acetylcholine receptor (AChR)
RAPSN - responsible for clustering AChR at the neuromuscular junction (NMJ)
COLQ - which anchors acetlycholinesterase at the NMJ
CHAT - choline acetlytransferase involved in the synthesis of acetylcholine
DOK7 - involved in clustering AChR and maintaining NMJ structure
CHRNG - the fetal AChR gamma subunit in which mutations can cause Escobar's syndrome (screening is on a research basis at present - but will shortly be transferred to the CPA accredited laboratory)
MUSK - the gene for muscle specific tyrosine kinase can also be screened on a research basis.

2. Whole exome sequencing/gene screen: in research unit where appropriate.
3. Where novel mutations are identified we are developing an increasing repertoire of functional analyses to confirm their pathogenicity.

Owing to the heterogeneity of these disorders, and because clinical evaluation can inform the genetic screening, we recommend that all patients attend for clinical assessment whenever possible.

DNA or blood samples for screening

1-4 mls blood in 10 mM EDTA tube(s) should be sent to:

Anjali Lloyd-Jani BSc MSc DipRCPath
Principal Clinical Scientist

Oxford Regional Genetics Laboratories
Churchill Hospital
Oxford OX3 7LE

Congenital Myasthenic Syndrome (CMS) Annual Reports

The CMS service produces annual reports for NHS England.

If you would like a copy of these reports, please email: cmsgenetics@ouh.nhs.uk

Key staff

Clinical team

Professor Jacqueline Palace (Consultant Neurologist)
Dr Sithara Ramdas (Consultant Paediatric Neurologist)
Dr Leighann Henehan (CMS Clinical Fellow)
Hayley Ramjattan (CMS Specialist Physiotherapist)
Sandhya Rai (CMS Clinical Nurse Specialist)

Clinical genetics

Ms Anjali Lloyd-Jani (Principal Clinical Scientist)
Dr Louise Williams (Clinical Scientist)
Claire Hodgkiss (Clinical Scientist)
Drew-Deece Cone (Genetic Technologist)

Genetic analysis for these disorders is carried out by the UKAS-accredited Clinical genetics laboratory at the Churchill Hospital, Oxford (Director, Dr. Carolyn Campbell).

Genetics Laboratory Liaison

Dr Tracy Lester (Consultant Clinical Scientist)

Functional diagnostics analysis

Dr Yin Dong oversees the functional analysis of genetic variants of unknown significance at the Weatherall Institute of Molecular Medicine (WIMM), within the Nuffield Department of Clinical Neurosciences, University of Oxford.

Professor David Beeson (Emeritus) continues to advise the service.