Neurocutaneous Disorders Phakomatoses and Hamartoneoplastic Syndromes

1051 Pages·2008·24.348 MB·English

by  Laura Flores-Sarnat MD (auth.), Martino Ruggieri, Ignacio Pascual-Castroviejo, Concezio Di Rocco (eds.)

SpringerWienNewYork
Martino Ruggieri
Ignacio Pascual-Castroviejo
Concezio Di Rocco
(Eds.)
Neurocutaneous Disorders
Phakomatoses and Hamartoneoplastic Syndromes
SpringerWienNewYork
Martino Ruggieri
Institute ofNeurological Science,National Research Council,Catania,Italy
Ignacio Pascual-Castroviejo
University Hospital La Paz,Madrid,Spain
Concezio Di Rocco
Institute ofNeurosurgery,Catholic University ofthe Sacred Heart,Rome,Italy
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Martino Ruggieriis First Researcher in Paediatrics at the Institute of Neurological
Science of the Italian National Research Council and at the Department of Paediatrics
of the University of Catania,Italy and Associate Professor of Paediatrics (board
certified,2006).He graduated at the University of Catania and completed his
postgraduate training at the Departments of Medical Genetics and Paediatrics,
Churchill and John Radcliffe Hospitals,University of Oxford,UK and of Neurology
and Neurogenetics,Massachusetts General Hospital,Harvard Medical School,Boston,
USA.He trained on neurocutaneous disorders along with professors Lorenzo Pavone in
Catania,Italy and Susan M.Huson in Oxford,UK.His postgraduate thesis was on the
neurological manifestations of hypomelanosis of Ito and his PhD thesis on the different
forms of neurofibromatosis.He is the International Deputy Editor of the Journal of
Brachial Plexus and Peripheral Nerve Injuryand the International Associate Editor
(Paediatric Neurology) of Child’s Nervous System.He is editor of a textbook of general
paediatric neurology (in Italian).He currently runs in Catania,Italy a clinical and
research programme devoted to neurocutaneous diseases.Research interests include the
clinical manifestations of the different forms of neurofibromatosis in childhood,mosaic
neurocutaneous phenotypes and paediatric multiple sclerosis.
Ignacio Pascual-Castroviejohas been associate Professor of Paediatrics (Paediatric
Neurology) at the University of Madrid and Chairman of Paediatric Neurology at the
University Hospital “La Paz”,Madrid,Spain from 1965 to 2004.He graduated at the
Complutensis University of Madrid in 1962.He completed his postgraduate training in
Madrid,in Würzbourg (Germany) and in Strasbourg (France).He obtained the board in
Neurology in 1965 and the board in Paediatrics in 1971.He got his PhD in 1968 with a
thesis on “Cerebral malformations and the Classification of corpus callosum and septum
pellucidum malformations by pneumoencephalography”.He has been one of the founding
members of the International Child Neurology Association (ICNA) (1973) and the
European Society of Neuroradiology (ESNR) (1969) and the President of the Spanish
Society of Neurology and Spanish National Commission of Neurology.He is honorary
member of several International Scientific Societies of Neurology,Neuroradiology,Paediatric
Neurology and Paediatrics.He is member of the board of several international journals of
Paediatric Neurology.He is editor of many textbooks (in Spanish and English) on general
paediatric neurology,spinal tumours in infancy,attention-deficit hyperactivity disorder
(ADHD),neurocutaneous disorders and contributed with chapters in the most acclaimed
books on Neurocutaneous Disorders.Research interests include general paediatric neurology,
neurocutaneous disorders,ADHD,vascular pathology,and neuroradiology.
Concezio Di Roccois Professor and Chairman of Paediatric Neurosurgery at the
Catholic University of the Sacred Heart in Rome and Director of the Training
Programme in Neurosurgery at the “Gemelli”University Hospital,Rome,Italy.He
graduated at the Catholic University in Rome and completed his postgraduate trainings
in Neurosurgery,Paediatric Neurosurgery and Paediatrics at the University of Genoa
and at the North-western University Medical School,Children’s Memorial Hospital of
Chicago,USA. He has been President of the International Society for Paediatric
Neurosurgery,European Society for Paediatric Neurosurgery and Vice- President of the
European Association of Neurosurgical Societies.Currently,he is Chairman of the
Paediatric Committee of the World Federation of Neurosurgical Societies and member
of the teaching faculty at INI-China in Beijing.Professor Di Rocco is the Editor-in
Chief of Child’s Nervous Systemand member of board of several international journals
of Neurosurgery and Neurosciences.Research interests include brain malformations,
hydrocephalus,tumours,craniosynostoses,and neurocutaneous disorders.
To our wonderful Wives
Agata, Alicia and Paola
Foreword
NEUROCUTANEOUS DISORDERS
M. Ruggieri, I. Pascual-Castroviejo, and C. Di Rocco
Phakomatoses and hamartoneoplastic diseases
The striking association of some neurological diseases with cutaneous abnormalities has long attracted the attention of
physicians.Many such associations have been recognized; many are relatively rare conditions but,collectively,they ac-
count for a significant proportion of the neurological disorders especially in children.Their clinical manifestations are
polymorphous,they may involve many others organs or systems in addition to skin and nervous system and they may be
difficult to diagnose.Their clinical interest,their causes and mechanisms are closely related to several major basic bio-
logical problems and their study has contributed to shed light on such basic biological issues as the growth regulation
and differentiation of tissues, opening new perspectives and leading to the introduction of new ideas and revision of
others.Thus,the concepts that skin and CNS are entirely derived from the ectoderm had to be modified as mesoderm
and endoderm are also involved.Likewise,the view that each of the three-germ layers is committed to generate specific
derivatives had to be qualified as no developmental function appears to be restricted to a single layer and developmental
genes appear to exert their specifying and signalling functions also on other layers.The essential role of the neural crest
whose cells are of single origin as the major source of many neurocutaneous disorders is being now generally accepted.
In the past few decades,molecular genetic studies have permitted considerable progresses in understanding the causes,
mechanisms and classification, and new discoveries continue to challenge time-honoured concepts and generate new
ones for example that of somatic mosaicism.
The neurocutaneous diseases have also proved to be of broad biological and clinical importance as their study
may help unravel some of the causes and mechanisms of tumour formation and understand many aspects of oncogen-
esis,clearly a major theme of current and future investigation with major implications for public health and medical
practice.
The amount of recent acquisitions,both on the clinical and basic aspects of the neurocutaneous diseases,has grown
tremendously especially as a result of the recent development in neuroimaging and molecular genetics and it is now diffi-
cult to find an overall synthetic view of the complexities of this group of conditions.This difficulty makes the present
work that brings together up to date data both timely and of considerable value for the many different categories of
physicians and scientists that may become involved with these disorders.
Indeed,the general panorama of the neurocutaneous diseases is rapidly changing.New conditions have been recog-
nized and the respective frequencies of the various types have changed with recent studies:for example the relatively re-
cently described PHACE syndrome is now considered the commonest of all the neurocutaneous disorders.
There is no universal agreement on a definition of the neurocutaneous diseases.Early work mainly concerned the
pakomatoses, especially tuberous sclerosis and the neurofibromatosis.The domain has considerably grown to include
many other conditions in which variable amounts of cutaneous and neurological abnormalities tend to occur in persons
with one same condition but not necessarily in the same person and most often with relatively independent involvement
of various systems or organs.As a result,the clinical presentation of these conditions is extremely variable.Even major
features may be missing in many accepted cases. In addition, extra-neurological and extra-cutaneous anomalies have
been increasingly recognized and in some cases can represent the dominant clinical abnormalities. The causes and
mechanisms are clearly multiple. Such heterogeneity further complicates the issues of classification and diagnosis. In-
deed,if criteria for several specific entities have been established,no definite criteria have been adopted for the group as
a whole,so the limits of the group of neurocutaneous syndromes can vary to some extent with the authors.
The editors of this book have opted for a broad definition of the neurocutaneous disorders,encompassing diseases
in which the clinical association of the cutaneous and the neurological manifestations is not fortuitous,regardless of the
VIII Foreword
mode of transmission,genetic or otherwise,of the mechanisms of disease,of the relative involvement of tissues or sys-
tems and of the possible involvement of tissues other than skin or the nervous system,provided that the cutaneous and
neurological features are present.
This definition is not stringent and,in some cases,the decision as to whether minor dermatological of neurological
features are sufficient to satisfy the requirement for dual tissue or organ involvement association may be somewhat arbi-
trary. However, it is eminently practical from the point of view of diagnosis as no clear borderline exists between the
various causes and categories of neurocutaneous disorders and indeed the conditions included in the group have varied
widely with authors.It does not attempt to give any cue about aetiology and classification and is admittedly imperfect
and temporary.
However,such a simple approach permits to give a comprehensive description of all major neurocutaneous diseases
on one simple clinical basis without having to justify their inclusion on the basis of dubious and not universally accepted
criteria even though some conditions included may be regarded by some as disputable.
The comprehensive text is written by distinguished clinicians and investigators who have contributed significantly
to their study,several of them having indeed given the first or early descriptions of the disease described,covers in great
detail the clinical presentations and brings about complementary up to date biological data which will be of help in se-
lecting the best investigations for confirmation of the diagnosis. Over seventy erudite chapters together with profuse
and excellent illustrations and explanatory schemes and diagrams will guide the reader in the interpretation of the
highly polymorphous clinical features and the significance of the necessary diagnostic investigations for these conditions
many of which are rare or uncommon.The rarity and complexity of the neurocutaneous diseases point to the difficulties
to master the topic in full,none the less,and this is a dilemma familiar to physicians,whether common or rare,these
diseases exist,therefore the persons affected deserve to receive correct diagnosis and management.
Contrary to an unfortunately too common opinion,making a correct diagnosis is by no means an ‘insect collection’
exercise but is indeed of vital importance.For example,recognizing the minimal signs of neurofibromatosis I will radi-
cally alter the therapeutic approach to a brainstem tumour that may not necessitate irradiation when part of this disor-
der as opposed to isolated tumours,thus avoiding the tragic irradiation brain damage that was all too often observed in
the past.Likewise,the diagnosis of many genetic conditions often rests critically on cutaneous,morphological or others
non-obvious clinical or imaging details,essential to avoid incorrect genetic counselling which currently may have practi-
cal consequences including legal ones.
Given the complexity and the rarity of some of the neurocutaneous disorders,the necessity of imaging and connec-
tions with specialized laboratory facilities and the multiple skills necessary for their management, no single physician
can cover both the diagnosis and management requirements of all patients.As a result,many centres are now offering a
team approach to difficult cases,with multidisciplinary units or specialized clinics for the neurocutaneous diseases which
can help doctors in their task to alleviate the burden that these conditions represent for the patients and society at large.
This work will go a long way to help clinicians face the complex challenges posed by the neurocutaneous disorders.
It responds to the need for an up to date text about a group of conditions still largely unexplained and imperfectly diag-
nosed.I firmly believe it will become the standard text in the field for many years.It will obviously be a ‘must’for neu-
rologists and dermatologists especially those working with children, given the early age of clinical manifestations in
most cases.Moreover,because the manifestations of the diseases studied can affect so many different tissues or organs,
few clinicians will not need to use it for some cases and will like to find it at least in the hospital library as an essential
reference work.
This book will also be helpful for the more biologically oriented physicians and biologists who want to keep abreast
of many general biological problems such as carcinogenesis and molecular genetics and hopefully improve the condition
of persons affected by the neurocutaneous diseases.
Jean Aicardi MD,FRCP,Hon FRCPCH
Preface
PREFACE
This book sees the light of day after more than 5-year “gestation”.The idea behind it originated in the early 2000’and
was originally inspired by the superb manual (published in 1987) by the late professor Manuel Rodriguez Gomez (Neu-
rocutaneous Disorders.A Practical Approach.Boston:Butterworths).The manual was a practical and comprehensive guide
to compile the diagnosis and management of nearly all the common and rare neurocutaneous disorders recognised at
that time. It was an exhaustive and authoritative source of clinical information coupled with the pathological and
pathogenetic knowledge of the time,enriched by historical pearls on the “men behind the syndromes”.
Since the publication of that edition,there have been significant advances in many aspects of this field,especially in
molecular genetics and cellular biology.As a consequence of that the general panorama of the neurocutaneous disorders
has changed.New entities have been delineated expanding the nosology of the whole group.The old concepts on the
natural history and treatment of the various syndromes have been largely modified by the most recent large,population-
based,clinical and genotype studies.In addition,it has become clearer that the most appropriate approach for the man-
agement of these disorders is multidisciplinary.At the same time,further important works on this and related topic(s)
have been published delineating and establishing the present accepted definition(s) of the whole group of these
disorders.
As all of the present editors have been running special clinics devoted to the diagnosis and management of children
and adults with neurocutaneous disorders and have research interests in this field,we set out to create a new text,which
could reflect all these recent acquisitions coupling the practical clinical and bedside diagnostic approaches with the cur-
rent management issues and the modern basic science.To this purpose, we congregated an internationally renowned
group of contributors, many of them the very same experts who first explored a particular disorder or established its
present accepted definition.
Different from what was done in prior publications,in the present text we have included disorders,which had been
only seldom reported or reported under such a variety of names that it was not clear they were distinct entities.By doing
that we have opted in the end for a broad definition of the neurocutaneous disorders.This definition is not stringent
and, in some cases, the decision as to whether minor skin or nervous system features were sufficient to satisfy the re-
quirement for dual tissue or organ involvement association was on the basis of our personal clinical and research experi-
ence.In some cases,the inclusion of a certain condition among the spectrum of neurocutaneous disorders was dictated,
besides its clinical phenotype,by a common pathogenic mechanism or a shared metabolic/cellular pathway.In a rapidly
changing panorama of proteins, effectors, metabolites and receptors acting in common “cascades” (see for example
Fig.16,Chapter 5;Fig.9,Chapter 19;or Fig.8,Chapter 66) we opted for unifying rather than splitting groups of dis-
orders.For these and other reasons (e.g.,historical) we have also maintained in this book the handling of some condi-
tions even when an overt skin (e.g.,von Hippel-Lindau disease) or a frequent nervous system involvement (e.g.,ILVEN
syndrome) was lacking. In other cases the frequent similarities and/or overlaps between some disorders (e.g., Sturge-
Weber vs Klippel-Trenaunay vs Parkes Weber syndromes;or CHILD syndrome vs CDP Conradi-Hunermann-Happle
type/CDPX2 syndrome) prompted us to treat the whole spectrum of disorders.To this purpose we also chose to subtitle
the book “Phakomatoses and Hamartoneoplastic syndromes”[borrowing the latter term from the classical (4th edition;pub-
lished in 2001) of the text by Robert J. Gorlin, Michael M. Cohen Jr and Raoul C.M. Hennekam (Syndromes of the
Head and Neck.Oxford:Oxford University Press)] – i.e.,to emphasise that one of the aims of the present book was to
encompass the whole spectrum of the classic neurocutaneous disorders and the less known conditions with “phakomas”
and “hamartomas”.
The book is deliberately in the format of a textbook rather than a manual and is conceived to address neurocuta-
neous disorders in a different way from other existing publications in the field.Its main philosophy consists in the dis-
cussion and wide illustration of neurocutaneous disorders,as it is much easier to recognise a disorder by seeing images
rather than by only reading about clinical phenotypes.In line with such philosophy we also included many sections not
only to detail historical and biographical aspects for the readers with a “historical turn of mind”but also to credit all the
“women and men behind the eponyms”who attained their place in history not by accident,but by virtue of great gifts
and consistent hard work of the highest quality in many fields besides medical field.
X Preface
The 72 chapters were authored and co-authored by leading,world-renowned authorities in the various fields many
times co-authored by one or more of us.We also undertook an enormous editorial revision of all contributions to give
the book a homogeneous structure.This entailed editing the text and sometimes adding our own case material where we
considered it useful to enrich or complete the various presentations.We would like to thank all contributors for their pa-
tience in accepting these frequent “intrusions”in their work.We also drew most of the line drawings ourselves,and in-
cluded pathologic illustrations and anatomic preparations.Because the work on this book spanned several years,we also
undertook a review,sometimes painful but hopefully thorough,of the more recent literature throughout the text.
Last but not least,we wish to thank all the people at Springer in Vienna,Austria,and especially our first contact
person Mr Raimund Petri-Wieder and the current medical editor Mrs.Mag.Franziska Brugger;the production editors
Mag.Judith Martiska and Ing.Mag.(FH) Karim Ernst Karman;the selling editor Mrs.Petra Kern;and the typesetter
Thomson Digital,A Division of Thomson Press (India) Ltd.,for the enduring kindness,patience,and trust that they
bestowed in us, graciously accepting our too often controversial requests, believing that we would eventually succeed,
and especially in pursuing a common goal.Their efforts coupled with the Springer’s superb quality of printing and lay-
ing out made our initial aims concrete facts.
Catania,Madrid and Rome,July 2008 Martino Ruggieri,MD,PhD
Ignacio Pascual-Castroviejo,MD,PhD
Concezio Di Rocco,MD
Contents
1. Embryology of neurocutaneous syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
(Laura Flores-Sarnat and Harvey B.Sarnat)
2. Vascular birthmarks of infancy:PHACE(S)association (Pascual-Castroviejo type II
syndrome) and Cobb syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
(Ignacio Pascual-Castroviejo)
3. Neurofibromatosis type 1 & related disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
(Martino Ruggieri,Meena Upadhyaya,Concezio Di Rocco,Annalia Gabriele,
and Ignacio Pascual-Castroviejo)
4. Neurofibromatosis type 2 and related disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
(Scott Randall Plotkin)
5. The tuberous sclerosis complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
(Sergiusz Józ´wiak,Nicola Migone,and Martino Ruggieri)
6. von Hippel-Lindau disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
(S.Taylor Jarrell,Edward H.Oldfield,and Russell R.Lonser)
7. Klippel–Tranaunay,Parkes Weber and Sturge–Weber syndromes (including
Kasabach–Merrit phenomena) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
(Martino Ruggieri,Orhan Konez,and Ignacio Pascual-Castroviejo)
8. Klippel–Trenaunay syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
(Martino Ruggieri,Concezio Di Rocco,and Orhan Konez)
9. Parkes Weber syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
(Orhan Konez,Martino Ruggieri,and Concezio Di Rocco)
10. Sturge-Weber syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
(Ignacio Pascual-Castroviejo,Orhan Konez,Concezio Di Rocco,and Martino Ruggieri)
11. Osler-Weber-Rendu syndrome (Hereditary hemorrhagic telangiectasia) . . . . . . . . . . . . . . . . 311
(Haneen Sadick,Maliha Sadick,and Karl Hörmann)
12. Macrocephaly-cutis marmorata telangiectatica congenita
(macrocephaly-capillary malformation) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
(Pablo Lapunzina and Jill Clayton-Smith)
13. Blue Rubber Bleb nevus syndrome (BRBNS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
(María del Carmen Boente and María Rosa Cordisco)
14. Wyburn-Mason syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
(Martino Ruggieri,Orhan Konez,and Concezio Di Rocco)
15. Maffucci syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
(Leida B.Rozeman,Yvonne M.Schrage,Judith V.M.G.Bovée,and Pancras C.W.Hogendoorn)
16. Hypomelanosis of Ito and related disorders (Pigmentary mosaicism) . . . . . . . . . . . . . . . . . . . 363
(Ignacio Pascual-Castroviejo and Martino Ruggieri)
17. Phylloid hypomelanosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
(Carmelo Schepis)
18. Incontinentia pigmenti . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
(Ignacio Pascual-Castroviejo and Martino Ruggieri)