Ciliopathies: A reference for clinicians

301 Pages·2013·2.949 MB·English

by  Thomas D. Kenny, Philip L. Beales

Ciliopathies
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Ciliopathies

A reference for clinicians
Edited by
Thomas D. Kenny
National Institute for Health Research Evaluations, Trials
and Studies Coordinating Centre, University of Southampton, UK
Philip L. Beales

Professor of Medical and Molecular Genetics,
UCL Institute of Child Health, London, UK
1
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1
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Preface
Thomas D. Kenny
Until recently the diseases described in this book would have been considered nothing
more than a rag-bag of mostly rare, oft en serious, invariably complex clinical conditions.
Each was long recognised as a discrete clinical entity in its own right, but together they
have overlapping pathological elements. It is apparent that, far from the beliefs of the past,
cilia are much more than vestigial cellular organelles, but we are some way short of com-
prehending the full extent of the implications of this.
It was my privilege to be the medical adviser responsible for three NHS services that
managed these conditions (Alström syndrome, primary ciliary dyskinesia and Bardet–
Biedl syndrome). Th ese conditions had a profound aff ect on me. Th ey are rare, complex
and serious. Th ey have no cure, and no specifi c treatment, but far from being hopeless.
Well-organised multidisciplinary clinical services can produce benefi ts for the patients
they see (Kenny et al. 2008 ) and advanced the understanding of the conditions.
As I gained understanding from the peculiarities of one of these conditions (P aisey
et al. 2011 ) and applied that understanding to the organisation of the services for other
conditions I began to have a respect for the underlying biological processes that cause
the overlapping phenotypical elements of these diseases and the wider group of other
ciliopathies.
Due to their rarity, outside of specifi c services, many patients with ciliopathies get a ‘raw
deal’. Many clinicians will spend their whole careers without caring for a patient with one
of these diseases, I never saw one while I was in general practice and thinking back I do
not know if I would have recognised one if I had. Th e patients and the support groups
that represent them have repeatedly expressed a desire for a reference text that they could
point their primary and secondary care clinicians to. Th ey complain that their diagnoses
seemed to take ‘forever’ and that other than the hand-full of clinicians for each condition
no one seems to have heard of them or do the simple things they need to help them stay as
healthy as they can.
Th is book aims to be just such a text. Firstly, I hope it will help anyone, prompted to open
and read it, to understand and care for a patient with a specifi c ciliopathy. Secondly, if it
could also spark an interest in the underlying biological processes, and maybe guide the
identifi cation of a patient with a ciliopathy who would otherwise be missed, that would be
excellent.
And thirdly, given ubiquitous nature of cilia in our cells, there is a likelihood that there
are ciliopathies out there that have not yet been recognised as such. And maybe, just
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vi PREFACE
maybe, this will fall into the hands of a bright inquisitive clinician and it will be the catalyst
to the recognition of a disease as a new ciliopathy.
References
Kenny , T. D. , Jessop , E. G. & Gutteridge , W. H. 2008 . Monitoring clinical quality in rare disease
services—experience in England . Orphanet J Rare Dis 3 , 23 .
Paisey , R. , Barrett , T. , Carey , C. , Hiwot , T. , Cramb , R. , Bower , L. , e t al. 2011 . Rare disorders presenting
in the diabetic clinic: an example using audit of the NSCT adult Alström clinics . P ractical Diabetes
28 , 340 – 343 .
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Contents
List of abbreviations ix
Gene list xi
List of contributors xvii
1 Towards the diagnosis of a ciliopathy 1
Philip L. Beales and Th omas D. Kenny
2 Alström syndrome 8
Richard Paisey
3 Jeune syndrome and the ciliary chondrodysplasias 30
Miriam Schmidts
4 Joubert syndrome and Joubert syndrome-related disorders 64
Victoria Harrison and Andrea H. Németh
5 Bardet–Biedl syndrome 92
Philip L. Beales and Elizabeth Forsythe
6 Leber congenital amaurosis and other non-syndromic retinal ciliopathies 108
Th omas D. Kenny , Philip L. Beales and Ronald Roepman
7 Meckel–Gruber syndrome 132
Gabrielle Wheway and Colin A. Johnson
8 Nephronophthisis 150
Shalabh Srivastava and John A. Sayer
9 Oral–facial–digital type I syndrome 162
Brunella Franco
10 Autosomal dominant polycystic kidney disease 174
Richard Sandford
11 Autosomal recessive polycystic kidney disease 194
Carsten Bergmann
12 Primary ciliary dyskinesia 218
Claire Hogg
13 Usher syndrome 238
Maria Bitner-Glindzicz and Zubin Saihan
14 Syndromes not yet proven to be ciliopathies 262
Kate Baker
Index 275
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List of abbreviations
AAV adeno-associated virus DPM ductal plate malformation
ACE angiotensin converting enzyme DRC dynein regulatory complex
ACLS acrocallosal syndrome ECG electrocardiogram
ACS acrocallosal syndrome EGF epidermal growth factor
ADPKD autosomal dominant polycystic eGFR estimated GFR
kidney disease EM electron microscopy
AFP α-fetoprotein ERG electro-retinogram
ALT alanine aminotransferase ESRF end-stage renal failure
ARPKD autosomal recessive polycystic kidney EVC Ellis–van Creveld (syndrome)
disease
GCKD glomerulocystic kidney disease
AST aspartate transaminase
GCPS Grieg cephalopolysyndactyly
ATD asphyxating thoracic dystrophy syndrome
BOR branchio-oto-renal (syndrome) GFR glomerular fi ltration rate
BUN blood urea nitrogen GGT gamma glutamyl transpeptidase
CBF ciliary beat frequency (or γ-glutamyl transpeptidase)
CBS cystathionine beta synthase GI gastrointestinal
CD cone dystrophy HALT Halt Progression of Polycystic Kidney
CED cranial–ectodermal dysplasia Disease (a study group)
CEP centrosomal protein HDL high-density lipoprotein
CF cystic fi brosis Hh hedgehog
CFTR cystic fi brosis transmembrane HLS hydrolethalus syndrome
conductance regulator ICA intracerebral aneurysm, or
CGH comparative genomic hybridisation intracranial aneurysm
CHF congenital hepatic fi brosis IFT intrafl agellar transport
CKD chronic kidney disease IPT immunoglobulin-like, plexin,
transcription factor
CLKT combined liver and kidney
transplantation JATD Jeune asphyxating thoracic dystrophy
CNS central nervous system JBTS Joubert–Bolthauser syndrome
COACH c erebellar vermis hypo- / aplasia, JS Joubert syndrome
o ligophrenia, congenital a taxia, JSRD Joubert syndrome-related disorders
ocular c oloboma, and h epatic fi brosis LCA Leber congenital amaurosis
(syndrome)
MET mechanotransduction
CORS c erebellar– o cular– r enal (syndrome)
MKS Meckel–Gruber syndrome
CPAP continuous positive airway pressure
MOPD I microcephalic osteodysplastic
CRD cone–rod dystrophy primordial dwarfi sm type I
CRISP Consortium for Radiologic Imaging MORM m ental retardation, o besity,
Study of PKD congenital r etinal dystrophy and
CSF cerebrospinal fl uid m icropenis in males (syndrome)
CT computed tomography MRI magnetic resonance imaging
DKA Dekaban–Arima (syndrome) MSS Mainzer–Saldino syndrome
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