Manchester 1999
WEDNESDAY
A.M.
EUROPEAN UNION BIOMED PROGRAMME ON CLEFT LIP AND PALATE 1996-99
E. Albery, V. Brattström, G. Garattini, G. Gonzalez Landa, K. Gundlach,
K. Mølsted, J. Rautio, G. Semb, W.C. Shaw, J. Vrtiskova
The application to the EU Biomed Programme in 1995 arose from earlier experience
of intercentre collaboration within the Eurocleft Project. The work programme
promised three main outcomes:
1. Establishment of a register of cleft teams in Europe including details of
personnel, case load, clinical protocols and research capability.
2. Agreement, as far as possible, on policy statements and practice guidelines
designed to promote minimum levels of care for all affected European children,
and recommendations on record taking as part of a European quality improvement
programme.
3. The promotion of intercentre comparisons and multicentre clinical trials.
Progress to date:
A total of 180 cleft teams responded to an initial questionnaire and revealed
considerable diversity of organisation and practices. The majority of teams
(53%) reported that they treat between 2 and 30 patients per year, 4 teams treat
more than 100 patients. The 180 teams reported the use of 175 different protocols
including varied sequencing of operation for unilateral cleft lip and palate:
5% close the whole cleft in one operation, 65% use two operations, 29% use three
and 1 % used four.
In April 1998 a workshop including representatives from all EU countries as
well as the Czech Republic and Poland agreed a set of policy statements that
emphasise the responsibilities of cleft teams towards patients and the elements
of care and competence of professionals consistent with optimal practice. In
February 1999 a supplementary grant from the EU provided funds to invite representatives
from Eastern and Central Europe to attend a further workshop where the initial
policy statements were endorsed. It is anticipated that recommendations on record
taking will be confirmed in June 1999.
A number of intercentre comparisons have now been completed and plans for others
are in hand. Future collaborations are being encouraged through a series of
research methodology courses.
It is likely that the European network will contribute to wider international
collaborations, possibly via WHO, and an application to the EU Framework V Programme
is planned.
DUTCH THREE-CENTRE RANDOMISED PROSPECTIVE CLINICAL TRIAL OF PRESURGICAL INFANT
ORTHOPAEDICS
A.M. Kuijpers-Jagtman' B. Prahl-Andersen2 C. Prahl', EM. Konst', J.L. Severens',
H.F.M. Peters', A.C.M. Rietveld1 V.M.F. Borstlap-Engels', M.L.M. Mobers3, P.H.M.
Spauwen1, J.W. Mulder2, J.J. Hage2, J.M. Vaandrager3, A.M. Mugge1 , M. Meyer,2,E.
Vermeij-Zievernik3, R.H.J. Admiraal1, A.J. Greven2 E.J. Gerritsma3
'Cleft Palate Centre University of Nijmegen
2Cleft Palate Centre Free University of Amsterdam
3Cleft Palate Centre University of Rotterdam
Address: Prof.dr. A.M. Kuijpers-Jagtman, Cleft Palate Craniofacial Centre University
Hospital Nijmegen, PO Box 9101, 6500 1113 Nijmegen, The Netherlands. Tel + 31
24 3614065; Fax + 31 24 3540631; E-mail a.kuiipers-iagtman@dent.kun.nl
INTRODUCTION The benefits of presurgical infant orthopaedics (PSOT) in children
with a complete unilateral cleft lip and palate remain controversial, although
the therapy has been part of the comprehensive care of children born with clefts
already for many years. Opponents claim that PSOT is a complex and expensive
therapy not based on scientific data. In 1993 evaluation of PSOT through meta-analysis
of the available data from the literature, proved not to be possible due to
small sample size, lack of controls, deficient sample description and inaccurate
outcome variables of the existing studies. To investigate the effect of PSOT
in children with a complete unilateral cleft lip and palate a two-group randomised
prospective clinical trial design seemed to be the appropriate study set-up.
SUBJECTS AND METHODS In 1993 the Dutch Intercentre Study started as a collaborative
activity of the Cleft Palate Centres of Nijmegen, Amsterdam and Rotterdam. The
study design was ethically approved by the Medical Ethical Committees of the
three participating hospitals. Two treatment modalities were tested i.e. PSOT
or no PSOT. Intake took place within two weeks after birth according to strict
inclusion and exclusion criteria. Oral and written explanation of the trial
was given to the parents of an eligible child and after signing the informed
consent their child was assigned to one of the two groups: PSOT or no PSOT.
The intake of 54 children took two years. For only one eligible child the parents
refused to participate. The following outcome variables are studied:
A. General effects: influence on feeding, body length and weight gain, parents
satisfaction
B. Surgical and orthodontic effects: duration of lip surgery, aesthetic outcome,
maxillary arch form and dimensions, maxillofacial growth
C. Speech and language development: prelingual sound production, early speech
and language development, intelligibility
D. Cost-effectiveness: medical and non-medical costs
The PSOT treatment was a modified Zurich approach. Lip closure according to
Millard was performed at 15 weeks of age. The plate was re-inserted directly
after lip surgery. The soft palate was closed at 52 weeks of age. Then the use
of the plate was discontinued. The treatment in the non-PSOT group was the same
except for the use of a plate. A standard schedule of record taking was used
in all centres.
RESULTS The only variables for which significant differences between the two
groups were found, were speech and costs. No significant effects on general
and surgical/orthodontic variables were found. At the age of 2 1/2 years the
PSOT group obtained higher overall assessments for speech quality and speech
intelligibility than the non-PSOT group, but speech in both groups was still
worse as compared to their noncleft peers. A highly significant difference in
costs was observed, the PSOT treatment being much more expensive than the alternative.
CONCLUSION A randomised intercentre prospective clinical trial is a strong design
to investigate these two clinical alternatives in early CLP-treatment. At the
age of 2 1/2 year the effect of PSOT seems to be limited. However, especially
the effect on speech should be investigated further. At the age of 6 years all
children will be evaluated again for all variables.
KUIJPERS-IAGTMAN A.M.
AN INTERNATIONAL RANDOMISED CLINICAL TRIAL OF PHARYNGOPLASTY AND PHARYNGEAL
FLAP FOR VPI
Frank Åbyholm, Lillian Kjøll
Department of Plastic Surgery, Rikshospitalet, 0027 Oslo, Norway
Tel: 00-472-2867455
Fax: 00-472-2867466
The most commonly performed surgical procedures for management of velopharyngeal
insufficiency (VPI) are pharyngoplasty and pharyngeal flap. These two operations
have never been compared in a prospective study.
The study was initiated by three North American centres and the Oslo cleft centre
in 1993, however recruitment of cases in the USA has proven more difficult than
anticipated. To date 50 patients have been enrolled to the trial in Norway and
a further 27 in an extension of the trial to the North West of England.
We will describe the protocols for standardised data collection before and after
operation and surgical standardisation, and discuss the challenges involved
in mounting a surgical trial alongside routine clinical work.
Though it is too early to analyse the data, participants in the study have become
aware that former assumptions about clinical features that should determine
choice of operation (e.g. lateral wall movement) are not in fact predictive.
ÅBYHOLM, F
KJØLL, L
INTERNATIONAL RANDOMISED CONTROL TRIAL OF PRIMARY SURGERY
G. Semb*, G. Henningsson** (on behalf of the ScandCleft Research Group)
*University Dental Hospital of Manchester, Higher Cambridge Street, Manchester
M15 6FH, UK. Tel: +161275 6791, Fax: +161275 6974, E-mail: Gunvor.SembQman.ac.uk
(and University of Oslo, Department of Plastic Surgery, Rikshospitalet, 0026
Oslo, or Bredtvet kompetansesenter, Bredtvetvn 4, 0950 Oslo, Norway).
**Institutionen för Logopedi och Foniatri, Huddinge Universitetssjukhuset,
S-141 86 Huddinge, Sweden. Tel: +468 5858 1569, Fax: +468 5858 1505,
E-mail: gunilla.henningsson@klinvet.ki.se
While it has been appreciated that randomised control trials of primary surgery
are essential to provide unbiased comparisons of methods of primary surgery,
two practical obstacles must first be overcome. Firstly consensus must be reached
upon the techniques to be compared, and secondly, agreement to collaborate must
be reached by centres with sufficient caseload to generate samples within a
reasonable period of time.
This has recently been achieved at 10 North European centres by adoption of
a common method against which the traditional local method can be compared (see
table). Three parallel trials have thus been initiated with the explicit intention
of conducting eventual meta-analysis including direct and indirect subgroup
comparison. A total of 150 patients with unilateral cleft lip and palate per
trial are being enrolled over a five-year period.
Ethical approval has been obtained at every centre and by April 1999 eighty-two
patients have been enrolled.
Trial Trialists Common Method Local Method
1 Aarhus, Lip/soft palate 3m Lip/soft palate 3m
Copenhagen, Hard palate 12m Hard palate 36m
Gothenburg
2 Helsinki, Lip 3m
Link6ping, As above Hard/soft palate 12m
Stockholm
3 Oslo, Lip/hard palate 3m
Bergen, As above Soft palate 12m
Manchester,
Belfast
To make it possible to deliver reliable results in terms of speech and resonance
quality to this multi-centre study, a new methodology of evaluating cleft palate
speech is being developed based on an earlier proposal by an international task
force (Henningsson G, Hutters B,1997, Abstract, 8"' International Congress
on Cleft Palate and Related Craniofacial Anomalies, Singapore). Five different
languages are represented in these trials: Danish, English, Finnish, Norwegian
and Swedish.
SEMG G, HENNINGSSON G
INTERNATIONAL COMPARISONS OF SURGICAL OUTCOME
M. Mars
Consultant Orthodontist and Head of Department, Maxillofacial & Dental Department,
Great Ormond Street Hospital for Children NHS Trust, London, WC IN 3JH
Tel: 0171-405-9200
Fax: 0171-405-9200 Ext. 5540
The Goslon® Yardstick has been used internationally since its introduction
as a measure of outcome in unilateral cleft lip and palate patients. The use
of the yardstick will be described, its reliability discussed as well as its
limitations.
TITLE: DEVELOPMENT OF METHODS TO INVESTIGATE THE INTERACTION BETWEEN NUTRITIONAL,
ENVIRONMENTAL AND GENETIC FACTORS IN EARLY HUMAN DEVELOPMENT: DEMONSTRATION
PROJECT ON OROFACIAL CLEFTS
Mossey, P A
Orthodontic Department, Dundee Dental School, Park Place, Dundee, DD 1 4HR,
SCOTLAND
Tel: 00 44 1382 425761, Fax: 00 44 1382 206321, e-mail: p.a.mossey@dundee.ac.uk
Abstract:
Orofacial clefting (OFC) is one of the most common congenital anomalies in Europe
and accounts for approximately 65% of congenital craniofacial abnormalities.
The etiology of the two main types of OFC, namely cleft lip and palate (CL(P))
and isolated cleft palate (CP), is complex and heterogeneous. The nonsyndromic
forms of these disorders are thought to have multifactorial etiologies which
may partially overlap. The two principal components contributing to multifactorial
disorders, genes and environmental factors have been examined independently,
but it is only in recent years that studies have set out to address the interaction
between the two i.e. the role of the genotype in conferring susceptibility to
environmental factors - gene / environment interaction.
Several environmental factors have been implicated in the etiology of orofacial
clefts. Among them, maternal periconceptional supplementation by folic acid
has now been proven to be effective in the prevention of occurrence and recurrence
of neural tube defects, but its efficacy for oral clefts prevention remains
uncertain. It is possible that deficiency or abnormal metabolism of folate may
be responsible for several groups of malformations by interference with normal
embryonic development, and its role may vary according to maternal or embryonic
genotype. Additional studies are required to explore how genotype may modify
the role of environmental factors such as folic acid.
The European community with cultural diversity between countries, yet relative
national homogeneity provides an excellent opportunity for the investigation
of gene-environment interaction and combined data analysis can be used. Consistency
of association between studies carried out on populations with varying genetic
backgrounds, lifestyles and environmental exposures is an important criterion
in judging whether an association is causal.
Research into gene / environment interactions can be carried out using carefully
planned case-control studies, and three themes in such studies have been identified:
A. The interaction of maternal nutritional status and certain maternal and foetal
metabolic genes (e.g. MTHFR, RARA) and folate binding protein genes (e.g. FOLRg).
B. The interaction between certain genes whose products are involved in the
metabolism of xenobiotics (e.g. cytochrome P-450 genes) and environmental teratogens
such as tobacco and alcohol, solvents and other chemicals or drugs.
C. The interaction between certain "candidate genes" such as developmental
growth factor genes (eg. TGFa, TGFb2 and TGFb3) or homeobox genes (e.g. MSXl,
MSX2) and environmental factors.
The European Science Foundation (ESF) is supporting a three year network on
the development of methods for investigation of gene environment interaction
in early human development, with orofacial clefting as the main focus of the
groups research interest, but the results of which may have implications for
other congenital abnormalities. Four of the collaborating nations in this recently
established network have already embarked on a project to investigate the role
of folic acid and folic metabolic factors in the aetiology of cleft palate (CP)
and cleft lip and palate (CLP), in a project entitled "Interaction of Maternal
Nutrition and Folate Metabolic Factors in the Aetiology of Orofacial Clefts".
Such studies would inform the current debate about the efficacy of folic acid
and other nutritional factors and clarify the role of other environmental factors.
Subsequent public health measures may reduce the
prevalence of orofacial clefting.
MOSSEY, P.A.
WEDNESDAY P.M.
Cranial Suture Biology in the Rat and Mouse Models
Michael T. Longaker, M.D.
John Marquis Converse Professor
New York University School of Medicine
Craniosynostosis is a term commonly used to describe the premature fusion of
the cranial sutures. Our knowledge of the mechanisms responsible for both normal
and premature or pathologic cranial suture fusion has advanced significantly
in conjunction with improvements in
molecular and genetic analytical techniques. Recent studies have demonstrated
an association between Fibroblast Growth Factor Receptor (FGF-R) mutations and
syndromic craniosynostosis. Other investigators have found that a mutation in
Msx-2, a homeobox gene, and the TWIST gene. a transcriptional activator are
responsible for other types of craniosynostoses. There are likely numerous other
genetic abnormalities yet to be discovered which may also contribute to craniosynostosis.
In order to elucidate the multifactorial genetic causes of craniosynostosis
our laboratory developed in viva and in vitro models of both mouse and rat cranial
suture fusion. Utilizing these models we have characterized in detail the histology,
immunohistochemistry and gene
expression of bone growth factors during mouse and rat cranial suture fusion.
The advantage of our in vitro mode is that it allows for a well-controlled experimental
environment. These models enable the analysis of cranial suture biology before,
during, and after the process of cranial suture fusion. Seminal observations
can then be explored in a less controlled, but potentially more clinically relevant
to vivo environment.
Thus far, our laboratory has demonstrated the critical role of the underlying
dura mater in determining the fate of the overlying sutures. We have shown in
several studies that by manipulating the normal anatomic relations between data
and overlying Cranial suture we can alter the expected potency or fusion of
the sutures, Furthermore, our studies have shown that the intracellular signaling
cascades generated by Transforming Growth Factor beta (TGF-81), and possibly
basic Fibroblast Growth Factor (FGF-2), mediate these patterns of fusion and/or
non-fusion. Recent evidence from our laboratory has, for the first tune, demonstrated
significant temporal (adult versus young } and spatial (sutural versus non-sutural)
differences in the proliferation and gene expression of regional data mater
cells
Our ultimate objective is to develop novel strategies far earlier diagnosis,
aid in conjunction with our new knowledge of the molecular pathways involved
in pathologic premature same closure, implement less invasive treatments to
reverse or even prevent premature fusion of cranial
sutures, Towards this end, an overview of our data relating to cranial suture
fusion in the mouse and rat models will be presented.
CRANIOSYNOSTOSIS: from the clinic to the gene
Andrew O.M. Wilkie, David Johnson, Sachiko Iseki, Gillian M. Morriss-Kay, Steven
A. Wall.
1. Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford,
OX3 9DS
2. Oxford Craniofacial Unit, Radcliffe Infirmary, Oxford.
3. Department of Human Anatomy and Genetics, University of Oxford.
Craniosynostosis frequently poses complex problems for management that are best
undertaken by a multispecialty team. Four Craniofacial Units are funded by central
government to fulfill this role in England and Wales. In Oxford, a clinical
geneticist has attended the outpatients clinics since 1992 to provide diagnostic
advice and, when appropriate, more in-depth counselling. A research laboratory
established the following year has enabled our group to take full advantage
of rapid developments in molecular genetics during the decade. Mutations in
five genes (MSX2, FGFR1, FGFR2. FGFR3 and TWIST) have been identified in craniosynostosis
and collectively account for -20% of cases, including a majority of syndromic
ones. This information is essential for accurate diagnosis and counselling and
may even help in surgical management. This will be illustrated with clinical
examples (a typical phenotypes with FGFR2 mutation; the very common Pro250Arg
FGFR3 mutation; and complete deletions of the TWIST gene).
Genetics provides a powerful approach to dissecting the biology of normal and
abnormal signalling in cranial suture development. Work in Oxford focuses on
the mouse embryonic coronal suture and some recent work on expression of the
twist, fgfr1 and fgfr2 genes will be presented.
DISTRACTION OSTEOGENESIS
Distraction osteogenesis or DO is a technique that Plastic Surgeons use to lengthen
or distract segments of bone in patients with genetic diseases that lead to
a small lower jaw or mandible. Experiments with large animal models of DO have
described many aspects associated with this process and have led to clinical
efforts of pediatric jaw lengthening by DO at NY. However, the molecular biology
governing these changes remains essentially unknown, Over the past year, we
have Continued to develop a rat model of mandibular DO. In over 300 operations
to date, we have demonstrated that mechanical distraction of the rat mandible,
in a controlled fashion can increase mandibular length by up to 12%. This is
comparable to what is gained in jaw length in children. Microscopic tissue analysis
of lengthened rat jaw specimens, or histology, demonstrated characteristic.
changes similar to those described in large animal models, In preliminary studies
using this rat experimental model, we have initiated a rigorous analysis of
the genes expressed during DO.
In preliminary RNA studies of distracted rat mandibles, we have demonstrated
a 2,5 fold upregulation of TGF-b1, a growth factor important in bone development,
three days after the operation as compared to normal bone, Also, TGF-b1 expression
increased to 3 times normal levels during early phases of distraction, then
successively decreased to approximately twice normal by the end of distraction,
finally returning to baseline by the end of a four week post-distractions period
when the new bone has been formed.
lmmunohistochemistry is a technique that allows the use of specific antibodies
to trace the location of the bone promoting substance (TGF-b1 protein) in microscopic
tissues. This analysis demonstrated increased TGF-b1 protein in the main bone
calls known as osteoblasts and connective tissues next to the bone edge during
the pre-distortion period. During the distraction phase, when boric is being
lengthened, staining was most prominent within osteoblasts at the bony surface
and in soft-tissue cells within the distraction gap, Toward the end of the distraction
phase, when the newly formal bone begins to ossify, any strongly stained blood
vessels were noted within the gap. TGF~ b1 protein decreased during the post-distraction
phase where its expression was limited primarily to osteoblasts within the remodeling
bone.
In summary, we are just beginning to understand the genetic regulation of DO
using the rat model. The goal of these experiments is to understand DO at the
gene and protein level so that the rates of bone healing can be accelerated.
Also, improved bone formation is important far patient care .since it may allow
DO to be used in situations of poor bone healing such as patients previously
exposed to radiation or to augment bone healing in elderly patients.
Michael T. Longaker, M.D.
References of Interest
1. Bradley, J., Levine, J., Blewett, C., Krummal, T., McCarthy, J.G. & Longaker,
M.T, Studies in cranial suture biology: In vitro cranial suture fusion. Cleft
Palace-Craniofacial Journal. 33: 150, 1996,
2 Bradley, J., Levine, J., Roth, D., McCarthy, J.G. & Longaker, M.T. Studies
in cranial suture biology: IV. Temporal sequence of posterior frontal cranial
suture fusion in the mouse, Plast Reconstr Surg 98: 1039, 1996.
3 Bradley. J., Levine, J., McCarthy, J.G. & Longaker, M,T. Studies in cranial
suture biology: regional dura mater determines in vitro cranial suture fusion.
Plast Reconstr Surg. 100: 1091, 1997
4 Levine, J., Bradley, J., Roth, D., McCarthy, I.G. & Longaker, M.T. Studies
in cranial suture biology: regional dura rnater determines overlying suture
biology. Plant Reconstr Surg. 101: 1441, 1998.
5 Mehrara, B, et al. Adenovirus-mediated transmission of a dominant negative
truncated transforming growth factor beta receptor inhibits in vitro mouse cranial
suture fusion. Surg Forum 49. 492, 1998.
6. Mehrara, B., Mackool, R.J., McCarthy, J.G., Gittes, G.K & Longaker, M.T.
Immunolocalisation of basic fibroblast growth factor and fibroblast growth factor
and fibroblast growth factor receptor-1 and receptor -2 in rat cranial sutures.
Plast Reconstr Surg.102:1805, 1998.
7 Most, D., Levine, J., Chang, J., Sung, J., McCarthy, J.G., Schendel, S. &
Longaker, M.T. Studies in cranial suture biology: up-regulation of transforming
growth factor-beta 1 and basic fibroblast growth factor mRNA correlates with
posterior frontal cranial suture fusion in the rat. Plast Reconstr Surg. 101:1431,
1998.
8 Roth. D.A., Bradley, J.P., Levine, J.P., McMullen, H.F., McCarthy, 3,0. &
Longaker, M.T. Studies in cranial suture biology; Part II. Role of the dura
in cranial suture fusion. Plast Reconstr Surg. 97: 693, 1996.
9 Roth, D.A-, Longaker, KT., McCarthy, J.G., Rosen, D.M., McMullen, H.F., Levine,
J.P. & Gold, L.I. Studies in cranial suture biology: Part 1 Increased immunoreactivity
for transforming growth factor-beta (b1,b2,b3) during rat cranial suture fusion.
J Bone Miner Res. 12: 311, 1997.
10 Roth, D.A., Gold, L.I,, Han. V,K.M., McCarthy, J.G., Sung, J.J., Wisoff,
J.H. & Longaker, M.T. Immunolocalisation of Transforming growth factor B1,
B2, and B3 and insulin-like growth factor I in premature cranial suture fusion.
Plast Reconstr Surg. 99:300, 1997.
11 Sagrioglu, J.. Mehrara, B., Rowe, N., McCarthy, J., Gittes, CJ. & Longaker,
M.T. Studies in cranial suture biology; Impact of dura mater in cranial suture
fusion. Surg Forum 49: 494, 1998.
12 Sagrioglu, J_, Mehrara, B., Chau, D., Saadeh, P., Gittes, G. & Longaker,
M.T. Analysis of TGF-b production by fusing and patent mouse cranial sutures
in vitro, Annals of Plastic Surgery 42: 496-501, 1999.
13 Mehrara, B., Steinbrech, D" Saadeh, P., Gittes, G, & Longaker, M.X.
The expression of high affinity receptors for TGF-0 during rat cranial suture
fusion. Annals of Plastic Surgery 42:502-508, 1999.
PRIMARY AND SECONDARY CORRECTION OF THE CLEFT LIP NOSE
Brian C Sommerlad, FRCS
Great Ormond Street Hospital for Children, London WC1 3JH & St Andrew's
Centre for Plastic Surgery, Broomfield Hospital, Chelmsford, Essex CM1 7ET
Tel: 01245 422477 Fax: 01245 421901 Email: brian@sommerlad.co.uk
Primary nasal correction
Author's techniques:
Unilateral: Alar base positioning
Anderl periosteoplasty
Trans-septal suture
Mobilise skin from alars - from lateral and medial
"Late" McComb bolster
Bilateral: Alar base positioning
Anderl periosteoplasty
Trans-septal suture
Mobilise skin from alars - from lateral only.
Store "C" flaps - horizontally in nostril floor if possible
"Late" McComb bolster
Some typical results in both unilateral and bilateral noses will be presented
and criticised.
Alternatives:
Splints - Koken
Internal incisions
Skoog
Pigott
External incisions
Comparative studies will be reviewed
Secondary nasal correction
Author's techniques
Aim: * To re-do what was not achieved satisfactorily at the primary operation
* * Avoid "fiddles"
* Reduce and combine operations
* Leave until definitive rhinoplasty if acceptable
Unilateral. 1 Advance alar base - Y to V plus trans-septal suture
2 Closed nose tip correction- mobilisation of skin from alars and McComb bolster
3 Open tip rhinoplasty
4 Closed full rhinoplasty + septal surgery
5 Open full rhinoplasty + septal surgery
6 Onlay grafts:
Septal cartilage
Costal cartilage
Conchal cartilage
Bilateral: As above, ± columella lengthening by Cronin or conservative
forked flap advancement.
The author's experience of secondary nasal surgery over a 5-year period will
be critically reviewed and recommendations given.
Alternatives
Rim procedures - Dibbell and Tajima
External incisions
Bone grafts
SOMMERLAD, B.C.
The Role and Competence of the Child and Adolescent in Decision-making about
Treatment
Eileen Bradbury
Children with clefts and other craniofacial conditions are often faced with
surgery and other form's of treatment as they grow up. Whilst some treatment
is essential for their physical function and growth, much is carried out in
order to enhance their psychosocial well-being. Thus their opinion needs to
be taken into account. From the age of about 5 years old, children are capable
of participating in the decision-making process in a meaningful way, as long
as they receive information in language they can understand. Their role in the
decision-making process should gradually increase until they become the primary
decision-makers by mid-adolescence. Effective involvement in the decision-making
process is known to enhance compliance with treatment and encourages the young
person to gain a sense of mastery and control.
This presentation addresses the issue of the child's competence to make decisions,
and how that can be facilitated by the organisation of clinics and the dissemination
of clear information. There is also the question of the timing of surgery and
other treatments, and this will be discussed within a developmental context.
In addition, the role of parents and other family members in the decision-making
process will be discussed.
OVERCOMING CHALLENGES - BREASTFEEDING BABIES WITH CLEFT LIP AND CLEFT PALATE
Christa Herzog-Isler, RN, LACTATION CONSULTANT IBCLC, ADULT EDUCATOR, K.Honigmann,
PhD, MD, DDS.
C.Herzog-Isler, Bellerivestrasse 40, CH-6006 Luzern, Switzerland Tel./Fax ++4141370
44 71
K. Honigmann, Clinic for Maxillofacial, Plastic and Reconstructiv Surgery, Univ.-Clinic,
Kantonsspital, CH-4031 Basel, Switzerland
Tel. ++4161265 72 33, Fax ++4161265 72 98
In our study from 1992 we pursued the question of what feeding methods were
employed for babies with cleft lip and palates. Out of 38 children 10 (26.3%)
were breastfed. Nonetheless, these babies had a solely cleft lip.
There was however, a noticeable change in the research period between 1992 and
1999. From the 143 babies that were in the study 1/3, 48 (33%) was breastfed,
all forms of cleft conditions being represented. Of the 143 babies, 1/2, 71
(50%) received expressed breast milk and 24 (17%) were fed with artificial formula.
Certainly the intensive advisory consultations for parents, and ongoing education
for nursing staff on ante- and postnatal wards contributed to better feeding
methods. Further favorable factors that led to better results were:
· Putting the newborn to the breast directly after birth (bonding)
· Prevention of mother/baby separation postpartum
· Additional expression of milk apart from breastfeeding
· Breastfeeding and complementary administration of expressed breast
milk via finger feeding or Haberman teat
· Assessment and fitting of palatal obdurator
· Support through trained lactation specialist IBCLC
A NURSING PERSPECTIVE ON THE EARLY MANAGEMENT OF INFANTS WITH AN ISOLATED CLEFT
PALATE.
Mrs. Trisha Bannister
Greater Manchester Cleft Lip & Palate Unit
Dental Hospital,
Higher Cambridge St.,
Manchester, M15 6FH.
Tel: 0161 275 6795
Fax: 0161 275 6614
The early management of an infant with an isolated cleft palate can differ markedly
from that given to a baby either with an isolated cleft lip or a cleft lip and
palate. This is because for many babies there are functional difficulties in
addition to those caused by the obvious structural problem. Babies with an isolated
cleft palate are more likely to have additional problems, which may affect early
feeding skills and growth potential. Careful management, involving health professionals
and parents, is essential to assist infants to progress towards a normal feeding
pattern. The aim of nursing care is to understand, respect and respond appropriately
too the communications offered by the infant through continuous observation
and assessment whilst at rest and feeding. An understanding of normal feeding
allows the nurse to identify effective feeding skills and the particular difficulties
related to distortions of structure and/or function. Parental teaching, support
and involvement throughout this process is essential for continued progress.
Feeding problems related to abnormal structure are usually overcome with the
provision of the correct feeding equipment and feeding plan. Difficulties relating
to functional problems are more difficult to resolve, especially during the
first three months of life when feeding is largely a reflex driven activity.
Important Factors
o Early management
o Comprehensive feeding assessment
o Planned care and the teaching of parents
o Use of correct feeding equipment equipment
o Domiciliary support and counselling
The progression to normal feeding and growth patterns is possible for most babies
but for a minority this is an unachievable. Limited progress should be related
to irresolvable neurological problems rather than those of a behavioral origin.
BANNISTER, MRS. T.
NURSING THE CLEFT CHILD: A U.S. PERSPECTIVE
Vicki Suster (USA)
THURSDAY A.M.
CRANIOFACIAL SYNDROMES
Di Donnai (UK)
STRATEGIES FOR IDENTIFYING CRANIOFACIAL GENES
Michael J Dixon
School of Biological Sciences and Department of Dental Medicine and Surgery,
University of Manchester, 3.239 Stopford Building, University of Manchester,
Oxford Road, Manchester M13 9PT
Development of the orofacial region involves a complex series of events that
are frequently disturbed resulting in a wide variety of craniofacial anomalies.
The identification of the molecular events underlying such conditions is providing
important insights into the fundamental mechanisms underlying normal and abnormal
facial development. Indeed, recent advances in molecular biology, particularly
when coupled with the techniques of cell and developmental biology, are resulting
in the elucidation not only of individual molecules during development, but
also the role that they play in developmental pathways. There are numerous syndromes
that result in craniofacial malformation, including the craniosynostoses, Treacher
Collins syndrome and cleft lip and/or palate. The inheritance patterns that
underlie these conditions are variable and include Mendelian and non-Mendelian
modes of transmission. The integration of molecular biology with classical genetics
has allowed the molecular pathology underlying a large number of these conditions
to be elucidated. The identification of the gene(s) that are mutated in such
disorders may be achieved by one of three broad strategies. In disorders where
the abnormal protein is known, the gene that encodes it can readily be isolated
on the basis of its expression. For many disorders this is not the case and
the gene then has to be identified on the basis of its position within the genome.
This approach, which is known as positional cloning, involves using genetic
mapping techniques to identify the chromosomal region containing the disease
gene and, subsequently, to refine this region by the identification of polymorphic
markers which flank the disease locus. Physical mapping strategies are then
invoked to isolate continuous stretch of DNA across this region, which is then
used in the development of a transcript (gene) map of the "critical region".
Genes that are isolated using this approach are then screened for disease-causing
mutations. Despite recent technological advances, positional cloning remains
extremely demanding. While an increasing number of genes have been cloned using
this approach, these successes have most frequently been aided by the existence
of a previously identified candidate gene. Candidate genes may be highlighted
in a number of ways; for example, their function or expression patterns may
suggest a role in a given disease or alternatively, on the basis of data from
animal models. Previously identified genes are also considered as candidates
if they are known to map to the same vicinity as the disease locus. This has
been termed the positional candidate approach.
MOLECULAR AND CELLULAR REGULATION OF OSTEOGENESIS DURING DISTRACTION
J.A. Helms, M. Lee and D. Hu. University of California at San Francisco, USA.
INTRODUCTION
The human body possesses an enormous regenerative capacity. The clinical procedure
known as distraction osteogenesis takes advantage of this regenerative potential
to induce the regeneration and remodeling of bone, cartilage, nerve, muscle,
blood vessels and skin. The biological events that regulate this tissue response
are largely unknown, and thus our ability to optimize current treatments, or
design new approaches is severely restricted. Therefore, our goal was to develop
an animal model of distraction that was amenable to genetic, molecular, and
mechanical manipulation, and use this model to study the molecular and cellular
mechanisms regulating bone regeneration.
METHODS AND MATERIALS
Skeletally mature mice underwent surgical placement of a double ring fixator
to their tibia followed by a minimally invasive corticotomy via an anterior
longitudinal incision. Control mice followed an optimized distraction protocol,
whereas experimental mice followed protocols that altered the length of the
latency phase and the rate of distraction. Tissues were collected at various
time points and analyzed using molecular and cellular techniques.
RESULTS
During latency, the distraction site resembled a stabilized fracture callus
both on a histochemical and on a molecular level. Alkaline phosphatase staining
and collagen type I expression indicated that, in the absence of a distractive
force, mesenchymal cells rapidly differentiated into osteoblasts. During active
distraction, mesenchymal cells in the central fibrous interzone expressed the
transcription factor cbfal indicating their commitment to a skeletogenic fate.
Chondrogenic markers such as Indian hedgehog, bone morphogenic protein 6 and
collagen type II were not detected in the distraction gap. The interzone was
bordered by primary matrix fronts, with regenerate bone aligned with the distraction
force and parallel columns of vascular sinusoids. Tartrate resistant acid phosphatase
(TRAP) staining revealed that osteoblasts remodeled the bony regenerate as it
formed. During the maturation phase, cells within the fibrous interzone expressed
collagen type 1, osteocalcin, cbfal and other osteoblast-related markers and
exhibited abundant alkaline phosphatase activity, suggesting that they had begun
to terminally differentiate. When the distraction protocol was altered, we were
surprised to find that omitting the latency period, and distracting at supra-optimal
rates did not alone inhibit the formation of bone. Rather, rapid distraction
coupled with the omission of latency led to the disruption of bone formation.
Instead of ossifying, the fibrous interzone appeared as a heterogeneous zone
of fibroblasts and chondrocytes.
CONCLUSIONS
From these data we draw three conclusions. First, the mouse is an excellent
model to study the molecular and cellular regulation of distraction, and has
distinct advantages over other animal models that are not amenable to genetic
manipulation. Second, our data provide a framework in which to begin to study
the complex process of bone regeneration in an adult animal. Third, murine tissues
respond to supra-optimal distraction rates by forming fibrocartilage rather
than bone, similar to other animal models. We propose that the mechanical environment
created by this rapid distraction protocol prevents the establishment of an
intact vascular network. As a consequence, an avascular tissue, cartilage, forms
in the distraction gap. We are currently testing whether local application of
an angiogenic factor(s) can convert the fibrocartilaginous non-union into osseous
tissue.
GENETICS OF CLEFT LIP AND PALATE Murray, J.C.
Department of Pediatrics, The University of Iowa, Iowa City, Iowa 52242 U.S.A.,
TEL: (319) 3356897, FAX: (319) 335-6970, jeff-murray@uiowa.edu
Cleft lip and palate is a complex human craniofacial disruption that can arise
from a variety of genetic, environmental and unknown disturbances. Most cases
of clefting are felt to be non-syndromic without other associated anomalies
and likely secondary to interactions between one or more genes and the environment.
Besides this, many cases of clefting occur secondary to recognized teratogens
(such as alcohol or phenytoin), defined genetic causes such as chromosomal (particularly
trisomy 13 or 4psyndromes) or single gene Mendelian disorders such as the Van
der Woude syndrome. To better understand the genetics of clefting, one can make
use of chromosomal rearrangements for gene localization purposes and these efforts
have been especially successful in examining loci on the short arm of chromosome
6 that seem likely to play a role in clefting. Other approaches make use of
using positional cloning strategies to identify and then characterize genes
involved in clefting. Successful examples have already included those for Treacher
Collins syndrome, Simpson-Golabi-Bemel syndrome and a range of skeletal dysplasias
such as Stickler syndrome. Joint cytogenetic/Mendelian causes such as the DiGeorge
syndrome, caused by microdeletions on chromosome 22 have also provided opportunities
to identify individual small loci. The Mendelian forms of clefting are especially
well studied with a model in efforts to clone the gene involved in Van der Woude
syndrome. Van der Woude syndrome is an autosomal dominant condition with high
penetrance, and whose expressivity includes typical clefts of the lip, soft
and hard palate, paramedian lower lip pits and occasional hypodontia. The disorder
is associated with no other syndromic features and seems to be an outstanding
model for the more common non-syndromic forms of clefting. This disorder has
been mapped genetically and with microdeletions and efforts are now underway
to identify the specific gene involved in a very narrow region at chromosome
1g32.
Finally, approaches to the more common non-syndromic varieties make use of environmental
epidemiologic studies looking at maternal risk factors such as smoking, alcohol,
infection and other drug exposures and genetic approaches that have used both
candidate gene association studies and genetic mapping using sib pair or linkage
analysis. Some successes in both of these areas have already been reported and
include the candidate genes TGFA, TGFB3 and MSX1 for linkage disequilibrium
approaches and mapped locations at chromosomes 6p, as well as weaker data supporting
loci on chromosomes 2, 4, 17 and 19. In this presentation, we will summarize
more recent results on gene and gene-environment interactions and localization
and provide suggestions for strategies to be used in the future.
MURRAY, J.C.
PALATE DEVELOPMENT AND PREVENTION OF CLEFT PALATE
Mark Ferguson (UK)
Cell-cell interactions regulating tooth development Paul T Sharpe
Department of Craniofacial Development, GKT Dental Institute, Kings College
London, Guy's Hospital, London Bridge, London
Interactions between oral epithelium and neural crest-derived ectomesenchyme
cells are responsible for controlling skeletal and tooth development in mammalian
embryos. The nature of the signalling molecules and cell responses mediating
these interactions is starting to be understood. Some of the key interactions
controlling the positioning, initiation and patterning of tooth development
will be presented together with data that identifies the importance of temporal
and positional changes in cell responses to signals. These data can explain
the longstanding controversies over the origin of instructive information for
tooth patterning and highlight hitherto unrecognised differences between development
of the upper and lower jaws.
THURSDAY P.M.
SPEECH DEVELOPMENT IN CLEFT PATIENTS TREATED WITH THE DHPC - IS THIS A GOOD
WAY FORWARD?
Lohmander-Agerskov, Department of Logopedics and Phoniatrics, Göteborg
University, Sahlgrenska University Hospital, SE 413 45 Göteborg, Sweden,
Fax: +463182 34 16
e-mail: Annette.lohmander@logopedi.gu.se
The delayed hard palate closure concept (DHPC) for patients with cleft lip and
palate has for long been questioned regarding the treatment outcomes, particularly
speech. Severe speech deficits were reported in the 1980s and in the interest
of better speech development there were a gradual movement toward earlier palatal
closure. However, in the absence of longitudinal studies of speech and clinical
trials of primary palatal surgery including early palatal repair it is difficult
to reach a consensus about the best age for timing of palatal closure. Interestingly,
not only the timing but also the technique for palatal closure have been highlighted
by several of the investigators of speech after DHPC. They assumed that the
unusually high incidence of velopharyngeal insufficiency found in their studies
could be attributed to the techniques for veloplasty. A survey of studies of
speech in patients treated according to a DHPC concept reveals that even though
the total number of patients is limited, there have been 16 studies published
during the last two decades. Unfortunately, all the investigations are retrospective
in nature and they include large differences in the variables directly related
to the evaluation of the velopharyngeal function and speech: the age at and
techniques for soft palate repair; the age at hard palate closure; and the age
at speech evaluation. With such great variations in important factors and methodology
of the studies it is difficult to evaluate the influence of the DHPC on speech.
At the Göteborg Cleft Palate Center in Sweden, we have used a treatment
regimen including DHPC for more than 20 years. The cleft in the soft palate
has been closed at 6 to 9 months of age and the cleft in the hard palate at
about 8 years of age. For this presentation the speech in 73 consecutive patients
with complete unilateral cleft lip and palate (UCLP) born between 1977 and 1990
were reviewed from earlier studies and hospital records. Evaluations of speech
had been undertaken at six different age levels from 3 to 19 years of age. All
patients had not been evaluated at each age level but each patient had been
evaluated at least three age levels. In conclusion, these longitudinal speech
results are much better than other reported after DHPC during the early 1980s.
The prevalence of hypernasality and nasal escape after hard palate closure is
low and less than 10% of the patients had needed a pharyngeal flap. However,
the disadvantage of a surgical treatment that leaves an open residual cleft
in the hard palate is the relatively high occurrence of the specific articulation
errors where anterior pressure sounds are articulated behind the opening in
the hard palate (retracted oral articulation). In an effort to improve articulation
at 5 years of age and trying to minimise the interference with maxillary growth
the cleft in the hard palate is presently closed at 3 years of age. Thus, "a
good way forward" for the velopharyngeal function and speech seems to be
a two-stage palatal procedure. The technique for primary veloplasty includes
relocation and uniting the palatal muscles in the midline and also anchoring
the soft palate to the vomer. Hopefully, the timing of hard palate closure at
3 instead of 8 years of age will also result in good articulation already at
5 years of age, without too much interference with growth. This hypothesis will
be evaluated in the ScandCleft project, which is a randomised clinical trial
on primary surgery in UCLP-patients in Scandinavia and the UK.
LOHMANDER, A.
Issues of Evaluating Velopharyngeal Incompetence: Examining the Gold Standards
J. E. Riski, Ph.D., FASHA, CCC-S, Director, Speech Pathology Laboratory, Director,
Center for Craniofacial Disorders
Egleston Scottish Rite Children's Health Care System, 5455 Meridian Mark Road,
NE, Suite 420, Atlanta, Georgia 30342, Office: 404/256-5252 (3589), Fax: 404/250-2509,
e-mail: Jriski@SRCMC.Org
Evaluation of velopharyngeal incompetence (VPI) seeks to: identify patients
who would benefit from management, quantify severity of velopharyngeal incompetence,
select the most appropriate management procedure and quantify changes after
management. There are numerous methods available for evaluating VPI including:
perceptual rating scales, objective computer instruments of aerodynamics such
as pressure flow or acoustics such as nasometry, radiographic imaging techniques
such as cephalometric radiographs or multiview videofluoroscopy, or fiberoptic
techniques such as flexible or rigid nasendoscopy. The evaluation seeks to identify/quantify:
the amount of hypernasality, nasal air escape, oral and nasal air pressure,
the size of velopharyngeal incompetence and perhaps the shape of velopharyngeal
incompetence.
Despite the variety of instruments available to the clinician there is no one
instrument that provides an all-inclusive assessment of VPI. Because of the
multi-dimensional nature of VPI information from several instruments is often
required to gain a clear understanding. The assessment should be problem-driven.
The clinician should have a clear understanding of the advantages and disadvantages
of each instrument. This allows the clinician to select appropriate instruments,
maximizing the use of instruments and avoiding inappropriate interpretation
of data.
The purpose of this presentation will be to review instruments used to evaluate
VPI and discuss the advantages and disadvantages of each instrument. An evaluation
protocol that is problem driven will be developed that includes: perceptual,
clinical screening, objective assessment, imaging and diagnostic speech therapy.
The importance of a complete evaluation will highlight the need for understanding:
the appropriateness of speech sample; the three-dimensional nature of the velopharyngeal
mechanism; the "effective length of the velum in speech function; the velar
length to nasopharyngeal depth ratio; velopharyngeal closure pattern and comparison
of nasometry and pressure flow results. Examples of clinical errors caused by
incomplete evaluation will be given.
AN EXPLORATION OF THE UK CSAG SPEECH STUDY - WHAT HAVE WE LEARNT?
Dr Debbie Sell
Head of Speech and Language Therapy Department, Honorary Senior Lecturer, Institute
of Child Health
Great Ormond Street Hospital
Great Ormond Street
London, WC IN 3JN.
Telephone: 0171 405 9200 extension 5043 Facsimile: 0171 813 8278
E-mail: Debbie.Sell@gosh-tr.nthames.nhs.uk
Based on the national study of cleft care and outcomes in children born with
unilateral cleft lip and palate (UCLP) in the United Kingdom (CSAG Report, 1998),
the methodology and detailed speech results of 457 children are reported providing
a benchmark for speech outcomes following primary palatal closure. The complexity
of the speech condition associated with clefting is illustrated.
The significance of these results is examined and discussed within the context
of findings on UK speech and language therapy services. Lessons learnt regarding
methodology, the measurement and analysis of speech will be discussed and where
possible compared and contrasted with the international literature.
Speech and Language Therapists Aspirations for New Standards of Care in the
New Millennium Anne Harding ("UK)
Fifty years of speech and language therapy in the U.K has seen considerable
growth in our understanding about cleft palate speech. Although few therapists
hold contracts with both an exclusive clinical commitment to cleft palate and
a time allocation for research, a recent survey (Caan et al 1999) found that
33 clinicians consider themselves to be competent in this field. Approximately
65 therapists fulfill a role as cleft palate team clinician but as many as 600
community therapists may be involved in delivering regular speech and language
therapy programmes,
The Royal College of Speech and Language Therapists now recognises the need
for a specialist training route in order to accredit cleft palate team clinicians
as specialists in their field, A feasibility study into post graduate training
for specialist speech and language therapists (Caan et al op cit) has identified
potential for training at two levels of expertise: specialists working as lead
clinicians at the hub; and those at the spoke combining a coordinating role
with some treatment responsibilities and liaison with community services,
As we prepare for the implementation of the CSAG recommendations, we have an
opportunity to define our professional aspirations: to achieve the highest possible
level of clinical care for all children with cleft palate and related disorders
in the UK,; and to ensure that this can be delivered as near to home as possible
through transfer of the relevant skills and knowledge to community therapists
and parents, At last, it seems that realization of these aspirations is an achievable
goal, or is it?
Responses to the UK position will be invited from Sweden and the USA.
THE ROLE OF THE PSYCHOLOGIST IN A CLEFT TEAM
Nichola Rumsey
Centre for Appearance & Disfigurement Research (CADR), Department of Psychology,
UWE, St. Matthias Campus, Fishponds, Bristol, BS16 2JP, UK
e-mail: Nichola.Rumsey@uwe.ac.uk
Historically, the provision of psychological care for cleft-affected patients
and families in the UK, US & Europe has been `patchy' at best. For the most
part, psychological input has been confined to therapeutic intervention offered
to those patients and families who have been identified by other members of
the cleft team as experiencing specific psychosocial difficulties. However,
the recent NHSE circular Cleft Lip & Palate Services: Commissioning Specialised
Services (HSC 1998/238) recommends that a psychologist should be a core member
of cleft teams in the UK from April 2000. This paper explores the potential
added-value of an expanded role for psychologists in the cleft team, and offers
examples of existing good practice.
In addition to the better known competencies in forms of therapeutic intervention,
psychologists are trained in many other areas which are of direct relevance
to cleft care. Skills relating to research design and methodology can usefully
be applied to the development of treatment protocols and patient-centred audit
and outcome measures. The research literature indicates that there is considerable
individual variation in adjustment in cleft-affected patients, and that long-term
adjustment and well-being are related more to psychological variables such as
self esteem, sociability and the family environment than to aesthetic and functional
outcomes. It would clearly be beneficial for the team to identify and foster
the development of relevant psychological factors.
A psychologist's training in applying theory and research to practice is relevant
to both prevention and intervention in cleft care. Core team membership and
a regular clinic presence will facilitate the involvement of the psychologist
in areas such as prenatal and postnatal support for families, decision making
in relation to treatment, and preparation for surgery. Routine assessment and
screening will make possible the identification of early warning indicators
of psychosocial difficulties for patients and families. A range of interventions
could be offered in addition to one-to-one sessions, including group work (eg
to support school transfer), and the development and application of information
and support materials.
Lastly, in the potentially turbulent times ahead, cleft teams may wish to take
advantage of the psychologist's training in the management of change, in group
dynamics, and in methods of improving communication and morale in multidisciplinary
teams!
RUMSEY NJ
Psychological Issues in Craniofacial Habilitation: Psychological Assessment
and Therapeutic Strategies Fostering Resilience.
BRODER, HL; University of Medicine and Dentistry at New Jersey, Newark, NJ.
USA.
Over the past two decades, considerable concern about fostering well being and
competence in children has emerged. Given the frequently espoused rationale
for care-- to improve patients' psychological well-being-- the issue of resilience
is central to our work. Since craniofacial habilitation involves multiple input
from a cadre of helping professionals over a lengthy period of time, each specialty
area is
challenged to provide effective assessment and efficacious treatment. This paper
will overview: the psychological assessment; psychological findings among individuals
with craniofacial anomalies and other chronic conditions; psychological resilience
or well-being; therapeutic strategies to enhance well-being and recommendations
for future investigation. The conclusions reveal that individuals are at risk
for negative psychological sequelae; yet some individuals demonstrate excellent
coping strategies and psychological hardiness. Psychologic interventions may
be utilized to enhance well-being. A review of specific, effective cognitive
behavioral approaches for individuals with chronic conditions will be presented.
Future recommendations for interventions that are culturally sensitive and longitudinal
will be discussed.
PSYCHOSOCIAL IMPACT AND FAMILIAL DYNAMICS OF CHILDREN WITH FACIAL DIFFERENCES
Jennifer Simpson (USA)