Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8

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Journal of Cranio-Maxillo-Facial Surgery

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Median cleft of the upper lip: A new classification to guide treatment

decisions
Marie de Boutray a, *, Jean-Luc Beziat b, Jacques Yachouh a, Miche

le Bigorre c,
Arnaud Gleizal b, Guillaume Captier c
a
Department of Oral, Maxillo-facial and Plastic Surgery, CHRU Montpellier, Gui De Chauliac University Hospital, 80 avenue augustin Fliche,
34295 Montpellier cedex 5, France
b
Maxillo-facial Surgery Unit, Groupement Hospitalier Lyon Nord, 103 grand rue de la Croix-Rousse, 69317 Lyon cedex 04, France
c ^pital Lapeyronie, 325 avenue du Doyen-Gaston-Giraud,
Department of Plastic Pediatric and Craniofacial Surgery, CHRU Montpellier, Ho
34295 Montpellier cedex 5, France

a r t i c l e i n f o a b s t r a c t

Article history: Median cleft of the upper lip (MCL) is a specific and rare entity on the spectrum of facial clefts. MCL have
Paper received 25 October 2015 different clinical expressions and can be either isolated or part of multiple malformations. Confusion still
Accepted 25 February 2016 exists regarding the explanation and classification of MCL; some cases have been reported in the liter-
Available online xxx
ature, but no studies carried out a complete review of the literature.
This study reviewed cases of MCL in 2 French units and conducted a systematic review of the liter-
Keywords:
ature, in order to derive a new classification.
Median cleft lip
Fourteen patients with MCL in the 2 units and 195 cases in the literature were reviewed. They
Midline cleft
Holoprosencephaly
involved complete (42%), incomplete (49%), and minor forms (9%). Epidemiological and clinical data were
Frontonasal dysplasia collected, from which a classification was derived, based on the type of cleft and its belonging to other
syndrome(s). Three main groups were distinguished, namely, isolated MCL, MCL within craniofacial
malformations, and MCL with extrafacial malformations. Each group and subgroup was associated with a
prognosis and led to specific management.
This study reviewed all of the various forms of MCL and their associated anomalies, in order to have a
global view of MCL and to derive a useful classification scheme to guide management of care.
© 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights
reserved.

1. Introduction (DeMyer et al., 1963, 1964). Holoprosencephaly includes a spectrum

Median cleft lips (MCL) are part of an extremely rare group of
facial clefts defined by a cleft involving the upper lip, situated on
the median line. MCL have different clinical expressions, from a
small notch of the vermilion to a cleft of the entire length of the
philtrum with nasal and maxillary extension (Elias et al., 1992; Lee,
1985; Urata and Kawamoto, 2003; Jian et al., 2014). MCL can be
isolated or associated with other craniofacial malformations such
as hypotelorism, hypertelorism, holoprosencephaly, or lipoma of
corpus callosum and other malformations of the body (Allam et al.,
2011). The main craniofacial malformations associated with MCL
are the holoprosencephaly spectrum and frontonasal dysplasia
* Corresponding author.
E-mail address: madeboutray@hotmail.com (M. de Boutray).
of defects, from cyclopy with an alobar holoprosencephaly to mild
bilateral cleft lip with lobar holoprosencephaly. Frontonasal
dysplasia, with hypertelorism, is specially associated with the 0e14
cleft of the Tessier classification (Tessier, 1976).
Confusion still exists regarding the explanation and classifica-
tion of MCL, despite some embryological theories having been
advanced (DeMyer, 1975; Stark, 1954). Some authors suggest a
theory of failure of the 2 medial nasal processes to fuse in the
midline (DeMyer, 1975). Others support the theory of the failure of
mesodermal migration at the primary palate (Veau, 1938; Stark,
1954). This failure of mesodermal penetration results in a break-
down in the median element of the prolabial element and then a
median cleft of the upper lip. Based on the embryological approach,
MCL could be secondary to the agenesis or hypoplasia of the me-
dian element of the prolabium, or secondary to a cleft of this
element (Braithwaite and Watson, 1949; Millard and Williams,

http://dx.doi.org/10.1016/j.jcms.2016.02.012
1010-5182/© 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: de Boutray M, et al., Median cleft of the upper lip: A new classification to guide treatment decisions, Journal of
Cranio-Maxillo-Facial Surgery (2016), http://dx.doi.org/10.1016/j.jcms.2016.02.012
2 M. de Boutray et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8
1968). On the other hand, the anatomical criteria for the median
cleft lip and extent to adjacent structures are essential for surgical
treatment (Veau, 1938).
Some cases of this type of cleft have been reported in the
literature, but no studies have carried out a complete review of the
literature. Here, we describe cases of MCL registered in 2 French
tertiary centers over 25 years, and we systematically review of the
literature. This study aimed to derive a comprehensive and useful
classification of MCL from a large group of patients, in order to
guide the management of these patients. The second objective was
to calculate the correlation between clinical expression and asso-
ciated malformations.
2. Material and methods
2.1. Chart review
A retrospective chart review of MCL was carried out from 1989
to 2015 (25-year period) in 2 French tertiary centers: the cranio-
maxillofacial surgery department of Lyon and the pediatric plastic
surgery department of Montpellier. We collected epidemiological
data (diagnostic age, ethnicity, and gender) and clinical data of the
cleft and associated anomalies. Clinical data are reported in Fig. 1.
The size of the cleft lip was classified according to the following
3 categories: (1) minor forms, grouping normal lip and simple
notch in the vermilion (i.e., cleft at the vermilion, with a height of
no more than 6 mm above the edge of the lip); (2) incomplete
forms, grouping clefts limited to the vermilion (clefts more than
6 mm deep, not exceeding the limit between red and white lip) and
clefts reaching the white lip but not the full height of it; and (3)
complete forms, in which the lip is clefting over its entire length.
The philtrum's involvement was classified into five categories:
(1) normal philtrum; (2) fistula in philtrum; (3) enlargement of
philtrum's ridges; (4) cleft in philtrum; and (5) absence of philtrum
(in this case, unlike the cleft, the median part of the philtrum is
missing).
The appearance of the columella was classified into 6 categories:
normal, enlargement, bifidity, cleft, agenesis, and other columella
malformation.
The upper labial frenulum was divided into 4 groups: normal
frenulum, bifid frenulum, shortened frenulum, and agenesis.
Fig. 1. Clinical characteristics of the median cleft lips recorded in our population of patients.
Please cite this article in press as: de Boutray M, et al., Median cleft of the upper lip: A new classification to guide treatment decisions, Journal of
Cranio-Maxillo-Facial Surgery (2016), http://dx.doi.org/10.1016/j.jcms.2016.02.012
The premaxilla was classified into 4 categories: normal pre-
maxilla, notch (cleft in the premaxilla less than 6 mm high), cleft,
and agenesis.
The associated malformations were cleft palate, hypo- or
hypertelorism (intercanthale distance was measured on patients'
pictures: it was considered normal when it was equal to the length
of the palpebral fissure), holoprosencephaly, skin tags, abnormal-
ities of corpus callosum, digital anomalies (poly or syndactyly), and
other head or body malformations.
2.2. Review of the literature
This review included all PubMed publicly available articles
describing patients with MCL.
2.2.1. Literature search strategy
The literature search was conducted using PubMed database in
English and French languages using MESH terms “median cleft lip”
diane”. All
and key words “median cleft lip” and “fente labiale me
papers found in the PubMed search were reviewed according to a
standardized protocol, described below, up to December 2013
(Fig. 2).
2.2.2. Selection of papers
The same reviewer evaluated the abstracts of all of the articles
for appropriateness to the study aim. All relevant articles on the
MCL in English or French were selected for full-text review to
determine whether they met eligibility criteria.
2.2.3. Eligibility criteria
Inclusion criteria were at least 1 patient with MCL described
with adequate clinical description of the cleft, and article in English
or French language.
Exclusion criteria were as follows: animal studies, nasofrontal
dysplasia without median cleft lip, lateral cleft lip, median cleft of
the inferior lip, other complex facial cleft, other malformation,
holoprosencephaly without cases, dysmorphism without cleft lip,
lack of data, no cases described, and same patient described in
another article (duplicates).
2.2.4. Data extraction
Information concerning MCL was elicited. We collected the
same data as for patients of our chart review: epidemiologic data,
 M. de Boutray et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8 3

Fig. 2. Flow chart of papers selection process.

clinical data concerning median cleft lip and other associated termination of pregnancy because of holoprosencephaly. The 7
anomalies. patients with minor forms had neither associated malformation
nor dysmorphic features.
The 2 patients with incomplete clefts were boys. One had a mild
3. Results
broad philtrum and small median mass on the nasal dorsum,
diagnosed histologically as fibroma (Fig. 4). Surgery of the cleft
3.1. Case reports
carried out at 6 months of age consisted of plasty of the labial cleft
and resection of the nasal mass. The second patient had a cleft on
Fourteen patients with MCL were registered in the 2 tertiary
the median part of the vermilion. He had broad philtrum and
centers. Epidemiological and clinical data for each patient are re-
columella, a double labial frenulum, and a mild hypertelorism
ported in Table 1.
(Fig. 5). He underwent surgery at the age of 5 months to treat the
Of these patients, 7 had minor forms, 2 had incomplete forms,
cleft, the broad columella, and philtrum, and underwent a VeY
and 5 had complete forms. Among the patients with complete
plasty on the frenulum. The result 3 months after surgery was
forms, 2 had nasofrontal dysplasia, 2 had median clefts within
good; both patients were able to feed normally.
holoprosencephaly, and 1 patient had associated hypotelorism
Five patients had complete forms of MCL. Among them, 2 had
without holoprosencephaly.
alobar holoprosencephaly, with hypotelorism, absence of premax-
The minor forms included 2 patients with normal lip, notch of
illa, septum, and columella and cleft palate (Fig. 6). Both patients
alveolus, and double frenulum, and 5 patients with notches of
died before the first month of life. The third child with complete
vermilion and alveolus who also had a philtrum median sinus and
form had frontonasal dysplasia with hypertelorism. He had MCL,
double upper frenulum (Fig. 3). One of them had a nasal tag on the
cleft of the nose and premaxilla, cleft palate, median ethmoidal
tip of the nose. This patient had a family history of medical

Table 1
Epidemiological and clinical description of the patients of the unit.

Patient Age of Gender Ethnicity Size of cleft Philtrum Columella Frenulum Premaxilla Associated anomalies
diagnosis

1 12 mo F European notch fistula normal bifid notch

2 8 mo M Asiatic notch enlargem. normal hypertrophy normal
3 3 mo F European notch fistula normal bifid notch
4 5 mo F North African notch fistula normal bifid notch
5 4 mo M European normal normal normal bifid notch
6 2mo M European notch normal malformation bifid cleft
7 birth F European normal normal normal bifid notch nasal tag, sibling history
of holoprosencephaly
8 3 mo M Middle East lower half cleft enlargem. normal normal normal nasal tag
9 2 mo M North African vermillion cleft enlargem. enlargem. bifid normal hypertelorism
10 birth F unknown agenesis agenesis agenesis agenesis agenesis alobar holoprosencephaly,
palatal cleft
11 unkn. unkn. unknown agenesis agenesis agenesis agenesis agenesis alobar holoprosencephaly
12 birth F European agenesis agenesis agenesis agenesis agenesis
13 birth M European lower half cleft cleft bifid bifid cleft hypertel., palatal cleft,
sphenoethm. encephalocele
14 3 mo M European entire lip cleft cleft bifid bifid cleft

Note: mo ¼ months old; unkn ¼ unknown; enlargem ¼ enlargement; M ¼ masculine; F ¼ feminine; hypertel ¼ hypertelorism; sphenoethm ¼ sphenoethmoïdal.

Please cite this article in press as: de Boutray M, et al., Median cleft of the upper lip: A new classification to guide treatment decisions, Journal of
Cranio-Maxillo-Facial Surgery (2016), http://dx.doi.org/10.1016/j.jcms.2016.02.012
4 M. de Boutray et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8
Fig. 3. Patient with minor forms of median cleft of the upper lip: notch of vermillion
and alveolus, philtrum's median sinus and double upper labial frenulum.
Fig. 4. Patient with incomplete MCL: cleft of the low third of the upper lip, with mild
broad philtrum and small median mass on the nasal dorsum.
Fig. 5. Patient with incomplete MCL on the median part of the red lip, broad philtrum
and columella and a mild hypertelorism.
Please cite this article in press as: de Boutray M, et al., Median cleft of the upper lip: A new classification to guide treatment decisions, Journal of
Cranio-Maxillo-Facial Surgery (2016), http://dx.doi.org/10.1016/j.jcms.2016.02.012
Fig. 6. Patient with alobar holoprosencephaly, complete MCL, hypotelorism, absence
of premaxilla, septum, and columella and cleft palate.
encephalocele, and Down syndrome. Shortly after birth, he un-
derwent surgical treatment for his encephalocele and median cleft.
The fourth child had frontonasal dysplasia with nasal bifidity, me-
dian cleft premaxilla, cleft palate, and sphenoethmoidal encepha-
locele. The fifth patient with complete MCL had agenesis of
columella, septum, premaxilla, with hypotelorism. He had no ce-
rebral anomalies.
3.2. Review of the literature
The PubMed database search yielded 406 papers. After assess-
ment of titles and abstracts, 155 studies were selected for full-text
evaluation. A total of 46 were excluded because they did not meet
the inclusion criteria; 109 were selected and included 195 patients
with MCL published between 1951 and 2013. A flow chart is shown
in Fig. 2.
Epidemiological and clinical characteristics of patients of this
literature review are reported in Table 2. Gender was known for 155
patients: there were 81 males and 74 females. (sex ratio, 1.1 male
per 1 female). Age of diagnosis was found for 184 patients. The
diagnosis was made before the first year of age in 127 patients
(69%). Late diagnoses were made mostly in patients with incom-
plete or minor forms of MCL. Data about ethnic origin were found
for 157 patients: 39% were of white ethnicity and 38% were Asian.
The last 23% were of black, Arabian, or Hispanic ethnicity. This in-
formation has to be balanced with the fact that most of the authors
were also European, North American, or Asian.
The size of the clefts was described for 191 patients. The MCL
was follows:
1. Complete in 81 patients (42%) (Sharma et al., 2013;
Abdelmaaboud and Nimeri, 2012; Zahra and Hassan, 2012;
Mansouri Hattab et al., 2011; Aguinaga et al., 2011; Khandekar
et al., 2010; Sakamoto et al., 2010; Ko€ nig et al., 2009; Lesavoy
et al., 2009; Gawrych et al., 2009; Ichida et al., 2009; da Silva
Freitas et al., 2008; Kourti et al., 2008; Savasta et al., 2008;
Yucesoy et al., 2008; Imai et al., 2007; Hendi et al., 2004;
Chuang et al., 2003; Chen, 2002; Martinelli et al., 2002; Akan
et al., 2001; Kobayashi et al., 2000; Ako € z et al., 1999; Van der
Meulen et al., 1994; Singh et al., 1994; Ramos-Arroyo et al.,
1994; Vanrenterghem et al., 1993; Elias et al., 1992; Ronen and
Andrews, 1991; Voy, 1990; Sadove et al., 1989; Hattori et al.,
1987; Mizuno et al., 1986; Ohtsuka, 1986; Scrimshaw, 1986;
Takato et al., 1985; Lee, 1985; Christophorou and Nicolaidou,
1983; Mieden, 1982; Burck et al., 1981; Wiemer et al., 1978; Ben-
 M. de Boutray et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8
Table 2
Review of the literature: epidemiological and clinical data.
Data Number of data known
Age of diagnosis 184
Gender 155
Ethnicity 157
Size of cleft 177
Philtrum 173
Columella 172
Upper frenulum 160
Premaxilla 167
Secondary palate 166
Other associations 195
Hur et al., 1978; Sharma, 1974; Pĕnkava, 1974; Patel et al., 1960;
Laub et al., 1970; Dumars et al., 1970; Millard and Williams,
1968; McDonald, 1968; DeMyer, 1967; Kurlander et al., 1967;
DeMyer et al., 1963; Kazandjan and Holmes, 1959; Schneider
and Reiter, 1951),
2. Incomplete in 93 patients (49%) (Yıldırım et al., 2013; John et al.,
2013; Chen et al., 2012; Chou et al., 2009; Ichida et al., 2009;
Jhamb and Mohanty, 2009; da Silva Freitas et al., 2008;
Chousta et al., 2008; Liao et al., 2008; Stewart et al., 2007;
Giffoni et al., 2006; Szeto et al., 2005; Springer et al., 2004;
Urata and Kawamoto, 2003; Ghildiyal et al., 2003; Coban et al.,
2003; Ghossaini et al., 2002; Sakai et al., 2002; Asada et al.,
2002; Mishima et al., 1999; Masuno et al., 1997; Elçiog lu et al.,
1996; Martinot et al., 1994; Wey et al., 1994; Rudnik-
Scho€ neborn and Zerres, 1994; Singh et al., 1994; Apesos and
Anigian, 1993; Vanrenterghem et al., 1993; Eppley et al., 1992;
Lin et al., 1991; Reardon et al., 1990; Meinecke and Hayek,
1990; Kumar et al., 1988; Lewin, 1987; Pai et al., 1987; Lee,
1985; Nakamura et al., 1985; Grenman et al., 1985; Chervenak
et al., 1984; Beemer et al., 1983; Gopalakrishna and Thatte,
1982; Khoo and Saad, 1980; Feiler-Ofry et al., 1980; Wiemer
et al., 1978; Sharma, 1974; Pĕnkava, 1974; Warkany et al., 1973;
Patel et al., 1960; Edwards et al., 1971; Francesconi and
Fortunato, 1969)
3. Minor in 17 patients (9%) (Nún ~ ez-Villaveira
n et al., 2013; Lederer
et al., 2012; Da Silva Freitas et al., 2008; Imai et al., 2007; Stewart
et al., 2007; Valiathan et al., 2006; Kobayashi et al., 2000; Licht
et al., 1998; Bottani and Schinzel, 1993; Lee, 1985; Grenman
et al., 1985; Mattei and Ayme , 1983; Pĕnkava, 1974; Warkany
et al., 1973; Francesconi and Fortunato, 1969; Stark, 1954).
4. No data about the shape of the MCL were available for 4 patients
(Maarse et al., 2011; Kahl et al., 2007; Sakoda et al., 1979)
The philtrum and upper frenulum were very often affected: they
were normal in only 3%e4% of the patients in whom these 2 entities
had been described.
A total of 57 patients (29%) had hypotelorism associated with
their MCL, and 65 patients (33%) had hypertelorism associated.
Some patients had known syndromes: Pai syndrome in 11 pa-
tients (5.6%), holoprosencephaly in 49 patients (25%), frontonasal
dysplasia in 24 patients (12%), orofaciodigital syndrome in 15 pa-
tients (7.7%), short-rib-polydactyly syndrome in 6 patients (3.1%),
and trisomy 21 in 2 patients (1%).
Holoprosencephaly is obviously related only to complete forms
(49 patients), whereas nasofrontal dysplasia can be associated with
either minor forms (2 patients), incomplete forms (8 patients), or
complete forms (14 patients).
Please cite this article in press as: de Boutray M, et al., Median cleft of the upper lip: A new classification to guide treatment decisions, Journal of
Cranio-Maxillo-Facial Surgery (2016), http://dx.doi.org/10.1016/j.jcms.2016.02.012
5
Distribution
127 under 1 y/o (69%) e 31 children 1e12 y/o (21%) e 19 up to 12 y/o (10%)
81 males e 74 females e sex ratio 1.1 (male:female)
21 Indians (13%) e 37 East Asians (24%) e 61 Europeans (39%) e 17 Africans (11%) e 15 Middle
Eastern individuals (10%) e 6 South Americans (2%)
2 normal lip (1%) e 15 notches (8%) e 27 vermillion clefts (15%) e 22 lower
half lip (12%) e 31 upper half lip (18%) e 80 entire lip (45%)
5 normal (3%) e 1 fistula (0.6%) e 81 enlargement (47%) e 29 cleft (17%) e 57 agenesis (33%)
52 normal (30%) e 37 enlargements (22%) e 13 bifidities (15%) e 12 clefts (7%) e 57
agenesis (33%) e 1 malformation (0.6%)
7 normal (4%) e 90 bifid (56%) e 5 shortened (3%) e 58 agenesis (36%)
24 normal (14%) e 48 notches (29%)  37 clefts (22%) e 58 agenesis (35%)
8 clefts soft palate (5%) e 53 clefts palate (32%) e 105 normal secondary palates (63%)
49 holoprosencephaly (25%) e 11 Pai syndromes (6%) e 15 orofaciodigital
syndromes (8%) e 6 short-rib-polydactyly syndromes (3.1%)
The syndromic forms such as orofaciodigital syndrome and
short-rib-polydactyly syndrome are mainly found in the incom-
plete forms: 12 of the 13 orofaciodigital syndromes are incomplete
MCL, the 1 left is a minor MCL. All the short-rib-polydactyly syn-
dromes (6) are incomplete MCL.
MCL was isolated in 7 of the 17 patients with minor forms (41%),
in 34 of the 93 patients with incomplete forms (37%), and in only 1
patient with a complete form (1.2%), without any other malfor-
mation. Early death was described in none of them.
Associated anomalies that did not belong to a known syndromic
form were found in 14 patients with complete forms (anophthalmia,
blepharoptosis, microphthalmia, microcephalic cranium, lipoma or
agenesis of corpus callosum, and hypo- or hypertelorism), 26 pa-
tients with incomplete forms (skin tags, frontal alopecia, lipoma or
agenesis of corpus callosum, hypo- or hypertelorism, shortened
palpebral fissure, teratoid polyp of the vomer, palatal masses,
strabism, and microphlamia), and 7 patients with minor forms
(agenesis of corpus callosum, palpebral ptosis, and hypo- or hyper-
telorism). The prognosis for those forms associated with non-
syndromic anomalies depended on the associated anomalies.
4. Discussion
MCL is a very rare and heterogeneous malformation. The inci-
dence of MCL was studied by Fogh-Andersen (1965), who reported
15 median clefts of the upper lip among a series of 3988 clefts
(0.38%). Apesos and Anigian (Apesos and Anigian, 1993) found that
median cleft lips represented 0.43%e0.73% of all clefts. Bütow
(2007) described a series of 39 median clefts of the upper lip
among 2905 clefts (1.34%). Considering that clefts in general have
an incidence of 0.34e2.29 per 1000 births (Mossey et al., 2009), the
incidence of median cleft of the upper lip in the general population
can be estimated at about 0.0013e0.031 per 1000 births. The sex
ratio for median cleft lip has not been properly described in the
literature. It was approximately 1 for all groups in our literature
review, whereas it was 1.4:1 (male:female) in our chart review.
Most cases are sporadic, but genetic factors could be responsible
for MCL in the holoprosencephaly cases (Eppley et al., 2005). Fa-
milial cases of MCL are described in 8 articles (Yıldırım et al., 2013;
lu et al., 1996; Hattori et al., 1987; Burck
Savasta et al., 2008; Elçiog
et al., 1981; Khoo and Saad, 1980; Warkany et al., 1973; DeMyer
et al., 1963; Francesconi and Fortunato, 1969). One of our patients
with a minor form of MCL had a family history of hol-
oprosencephaly. MCL can also be present in orofaciodigital syn-
dromes, Pai syndrome, and short rib-polydactyly syndrome (Kahl
et al., 2007; Pai et al., 1987; Beemer et al., 1983). One of our
6 M. de Boutray et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8
patients had minor MCL with nasal chondroma that could corre-
spond to a Pai syndrome (Pai et al., 1987) defined by a trilogy of
malformations: lipoma of the corpus callosum, MCL, and facial skin
tags. Unfortunately, our patient did not have brain imaging to
search for corpus callosum lipoma, and he was lost to follow-up.
MCL have various clinical expressions, from a small notch of
the vermilion to a cleft of the entire length of the philtrum with
nasal and maxillary extension. As we show in our case study, the
spectrum of the MCL anomalies may be anatomically subdivided
into 3 groups according to the involvement of the upper lip
simple notch in the vermilion. The minor form corresponds to a
simple notch in the vermilion, and the diagnosis could be missed
at birth. The incomplete form of MCL involves the vermilion and
the cleft, reaching the white lip but not the full height of it.
Surgical treatment is almost always simple and proposed at an
early stage, usually after 6 months of age. The complete forms
of MCL involve the entire length of the lip and correspond to
an agenesis of the structure derived from the medial nasal
process. Reconstruction of the lip, columella, and premaxilla is
challenging.
MCL may be associated with specific features of the facial
midline or the palate. MCL were often associated with impair-
ment of the philtrum (97%) and upper labial frenulum (96%). They
were associated with abnormality of the premaxilla in 86% of
cases, and with abnormality of the columella in 69% of cases. The
association with a cleft secondary palate (37%), hypertelorism
(36%), or hypotelorism (30%) was common. Thus, hypotelorism
was much more common in complete forms of MCL (65%)
than in incomplete (4%) or minor forms (0%). On the contrary,
hypertelorism was more frequent in the incomplete forms (39%)
and in the minor forms (41%), but still appeared in complete
forms (27%).
Although these 3 anatomic groups of MCL are useful for surgical
treatment, this classification does not predict the prognosis and the
overall management of these children correctly. In our case series, the
minor forms were well correlated with the prognoses because all
patients had associated or syndromic malformation except 1 patient
with a nasal chondroma, which could be considered a minor mal-
formation. On the other hand, the complete form of the MCL could
also be isolated, as we observed in 1 case. The minor form represented
only 9% of the MCL in the literature but 50% in our series. This dif-
ference could be due to the increased prenatal diagnosis and the
obligation in France to explore the nose and lip at the second
trimester of pregnancy. The major forms associated with other
anomalies, including craniofacial anomalies (e.g., holoprosencephaly,
nasofrontal dysplasia) can be subject to therapeutic termination of
pregnancy in developed countries. This difference could also be due
to publication biases, as the most serious forms (complete forms) may
be more reported than minor or incomplete forms. In the literature,
those minor forms could be isolated forms (11 patients) or part of
syndromes (orofaciodigital in 2 patients, Pai syndrome in 2 patients,
and nasofrontal dysplasia for 2 patients).
In the literature, the incomplete and complete forms of MCL
represented 49% and 42%, respectively.
Indeed, as noted previously, MCL can be part of a syndrome, and,
in this case, the overall care of the child is not at all the same as with
an isolated cleft. This raises the question of the decision tree based
on the type of cleft, associated abnormalities, and prognosis due to
malformation pathology. We therefore sought to achieve a classi-
fication that allows properly categorizing all kinds of median cleft
lip and thus guiding the overall care that follows.
The anatomic classification is insufficient to establish a prog-
nosis of the child with MCL. Our data, combined with that of the
literature, shows that we could suggest a new specific classification
(Table 3) of the MCL, based on the type of cleft and its belonging to
Please cite this article in press as: de Boutray M, et al., Median cleft of the upper lip: A new classification to guide treatment decisions, Journal of
Cranio-Maxillo-Facial Surgery (2016), http://dx.doi.org/10.1016/j.jcms.2016.02.012
Table 3
Modified median cleft of the upper lip classification.
I. Isolated median cleft lip
II. Median cleft lip within complex craniofacial malformations
a. with hypotelorism:
1. holoprosencephaly
2. minor median hypoplasia without cerebral anomalies
b. with hypertelorism
1. median cleft face syndrome or nasofrontal dysplasia
2. minor median dysrraphism
c. with normal intercanthal distance
III. Median cleft lip with other body's anomalies:
a. orofaciodigital syndrome
b. short rib-polydactyly syndrome
c. other anomalies or syndrome
general or craniofacial syndrome. Three main groups might be
distinguished: isolated MCL, MCL within craniofacial malforma-
tions, and MCL with extrafacial malformation.
Patients with isolated MCL patients a good prognosis, because
they have no brain malformation and the MCL is frequently a minor
form.
MCL within craniofacial malformations may be subdivided into
2 groups: MCL with facial hypoplasia (holoprosencephaly and mi-
nor forms of hypoplasia), and MCL with hyperplasia (nasofrontal
dysplasia and minor median dysgraphia). The first group is gener-
ally associated with a severe prognosis when associated with ce-
rebral anomalies such as holoprosencephaly (DeMyer, 1975). Our 2
patients with holoprosencephaly died in the first month of life. On
the contrary, patients with craniofacial hyperplasia had a good
prognosis: the 2 patients with hypertelorism and encephalocele
were still alive at the age of 19 and 12 years. It was the theory of
DeMyer et al. (1964), when they wrote “the face predict the brain”.
The association with hypertelorism or hypotelorism could be a
predictive sign of the patient's brain prognosis. Indeed 84% of pa-
tients with MCL with hypotelorism had holoprosencephaly asso-
ciated with severe prognosis.
The MCL with extrafacial malformation are rare. Among the
cases of MCL reported in the literature, 15 had orofaciodigital
syndrome (8%) and 6 had short-rib-polydactyly syndrome (3.1%).
Patients with short-rib-polydactyly syndrome died during the first
days of life. Many other anomalies associated with MCL have been
reported: trisomy, diabetes, tetralogy of Fallot, imperforate anus,
and many others.
Each group and subgroup is associated with a cerebral (and thus
vital) prognosis and then leads to specific management of each type
of median cleft. In our series of 14 patients, 9 patients belonged to
group 1 and 5 patients belonged to group 2. Of the 5 patients in
group 2, 2 had hypotelorism and holoprosencephaly and died in the
first month of life. One had hypotelorism without cerebral anomaly
and was still alive at 2 years of age. The last 2 patients of group 2
showed hypertelorism with frontal-nasal dysplasia and were still
alive at 19 and 12 years of age. For the 9 patients in group 1, life
expectancy was normal.
In our review of the literature, the future of each patient was not
systematically explained. However, we noted that premature death
was described in patients with holoprosencephaly (18 patients),
short-rib-polydactyly syndrome (5 patients), orofaciodigital syn-
drome (2 patients) or nasofrontal dysplasia (1 patient). No pre-
mature death was described in patients with the isolated form.
These observations suggest that patients with isolated MCL have
an excellent vital prognosis: patients with isolated median cleft lip
should undergo surgery of the cleft and expect good results and
quality of life. Patients with MCL and hypertelorism usually have no
cerebral damage, but facial malformation can be challenging to
improve. Vital prognosis is good; facial prognosis depends on the
 M. de Boutray et al. / Journal of Cranio-Maxillo-Facial Surgery xxx (2016) 1e8
extent of the cleft. Cerebral and vital prognoses of patients with
MCL and hypotelorism are serious when associated with cerebral
anomalies: in this group, median cleft lip is often associated with
holoprosencephaly and then brain damage. For those patients, vital,
cerebral, and facial prognoses are severe. Surgical treatment should
be decided after balancing the risks and benefits related to life
expectancy, because life expectancy is often very short in this third
group of patients.
5. Conclusion
MCL comprise a specific entity on the spectrum of facial clefts.
They are rare, especially in their extended forms, and are still
difficult to classify properly. That is why our new median cleft lip
classification should help to elucidate types of cleft and the prog-
noses and then guide the management of care.
The study of all of the various forms of MCL and of the other
associated anomalies show that minor or incomplete forms are not
always isolated, and that some complete forms can be isolated. It is
therefore important always to perform a facial, neurological, and
extrafacial examination to search for another associated anomaly.
Conflicts of interest
None.
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