Polydactyly: A Review

Marie Claire Farrugia

Jean Calleja-Agius, MD, MRCOG, MRCPI, MSc, PhD

Continuing
Nursing Education Abstract
(CNE) Credit
Polydactyly, also known as hyperdactyly, is a common congenital limb defect, which can present with
Attention Readers: The
test questions are provided in this various morphologic phenotypes. Apart from cosmetic and functional impairments, it can be the first
issue, but the posttest and evaluation indication of an underlying syndrome in the newborn. Usually, it follows an autosomal dominant
must be completed online. Details pattern of inheritance with defects occurring in the anteroposterior patterning of limb development.
to complete the course are provided
online at academyonline.org/CNE. A Although many mutations have been discovered, teratogens have also been implicated in leading to this
total of 1 contact hour may be earned anomaly, thus making it of multifactorial origin. There are three polydactyly subtypes (radial, ulnar, and
as CNE credit for reading this article
and completing the online posttest
central), and treatment options depend on the underlying feature.
and evaluation. To be successful the
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The purpose of this review article
is to give more insight into the
management of polydactyly.
Accepted for publication
September 2015.
P
oly dac t y ly, also k now n a s 
hyperdactyly,1 is a frequently encoun-
tered limb-associated birth defect,1,2 with an
incidence that varies between racial groups
from 0.37 to 1.2 in 1,000 live births. 3,4
Polydactyly is characterized by extra digits
on the hands and/or feet, and it has been
classified as a duplication limb defect.5 Both
polydactyly of the hand and foot present with
various morphologic phenotypes,6 leading to
functional and cosmetic implications.7 As a
consequence, there are several surgical cor-
rections with different prognoses.6
Polydactyly occurs because of a defect
during limb development, particularly during
the anterior-posterior patterning of the devel-
oping limb bud. It can either present as an iso-
lated form or a manifestation of a syndrome.7
Consequently, better understanding of poly-
dactyly is important especially when working
in the neonatal unit because this could be
a sign of an underlying condition and thus
merit further investigations and follow-up.7
Because polydactyly can be the outcome of
various causes, including genetic and terato-
genic factors, which interfere with the molecu-
lar machinery of digit development, scientists
look at it as “an experiment of nature.” This
defect runs in families, and, when it is
expressed by itself, it most commonly follows
an autosomal dominant pattern of inheritance,
which is not sex linked. Thus, both males and
females are equally affected, each having a 50
percent chance of inheriting the condition if
the parent carries the trait.5 However, it must
be taken into consideration that sporadic phe-
notypes occasionally happen as well. Prenatal
ultrasound screening can detect polydactyly
and can alert the health care worker and the
pregnant woman to proceed with further
anomaly screening to exclude possible con-
comitant anomalies. In addition, around 50
percent of those born with the rare condition
of Fanconi anemia have abnormalities affecting
the thumb or thumb and radius; however, the
incidence of this condition in neonates with
thumb anomalies is still low. Yet, it has been
recommended to initiate testing for appropri-
ate treatment, education, and family genetic
counseling in such cases.8 Moreover, polydac-
tyly might be the only presenting feature of
Diamond-Blackfan anemia.9 Ultimately, it is
important for the neonatal health care workers
to advice those families who have a familial
recurrence of polydactyly to undergo genetic
counseling regarding their risk assessment.
LIMB DEVELOPMENT:
ANTERIOR-POSTERIOR
PATTERNING
During human embryogenesis, limb
growth and development begins with the

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http://dx.doi.org/10.1891/0730-0832.35.3.135
FIGURE 1  n  Limb bud/primordial development in embryonic life.10
The human embryo at five, six, and eight weeks of gestation. Upper limb development precedes lower limb development by a few days, and the
former appears first at 24 days of gestation, therefore, at the end of the fourth week. Limb buds appear as outpocketings from the ventrolateral
body wall.
formation of the limb primordium, which develops in the
somatopleure of the lateral plate mesoderm. As shown in
Figure 1, the limb primordium emerges by the end of the
fourth week of development with the upper limb buds emerg-
ing first in the lower cervical region on Day 24. This is fol-
lowed by the lower limb primordium, which emerges from the
lower lumbar region on Day 28 of embryonic development.10
Once the primordia are established, three interdependent
signaling centers control the three-dimensional organization
of the limb. In turn, these signaling centers set up the spatial
coordinates that shape the limb primordium. The first signal-
ing center controls limb growth from shoulder to hand. It is
located in the apical ectodermal ridge and is referred to as the
proximodistal center. Disruption of this center results in con-
genital anomalies including amelia (complete absence of a limb)
and phocomelia (partial reduction defect of a limb). The second
signaling center, known as the anteroposterior control center,
controls growth from the thumb to the little finger. Disruption
of the anterior-posterior axis leads to digit abnormalities,11 and
polydactyly represents a disruption of this digit patterning.2,12
The third signaling center, called the dorsoventral center, directs
growth from the back of the hand to the palm. Disruption of
this signaling center results in missing digits.
ANTEROPOSTERIOR POLARITY: THE
MECHANISM THAT POLARIZES THE LIMB
During embryogenesis, the identity and number of digits
is controlled by a specific mechanism that initially polarizes
the limb primordium followed by specification of digit iden-
tity and growth regulation.13 The first molecular clues, which
suggest that the primitive limb primordium is polarized, is
the expression of two transcription factors: Glioma-associated
oncogene homologue 3 (GLI3) anteriorly and heart and
neural crest derivatives expressed 2 (HAND2) posteriorly.14
There is evidence that GLI3 can specifically repress HAND2
transcription.15 Once these two transcription factors locate
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in their destined places, the posterior segment expresses the
sonic hedgehog (SHH) gene. The SHH is critical because it
regulates spatial variation along the anterior-posterior axis,
and it is the product of the zone of polarizing activity (ZPA),
a group of mesodermal cells in the posterior segment of the
limb. Experiments show that whenever the ZPA is trans-
planted to the anterior segment, SHH secretion follows,
resulting in the formation of extra digits. In fact, disruption
of the SHH molecule is what brings about radial polydactyly,
according to animal models.11,15–17 Moreover, these extra
digits are mirror images of the normal extremities.18
THE MECHANISM OF SHH SIGNALING
AND THE GLI3 GRADIENT
Much of what is actually known about the SHH pathway
was initially based on the fruit fly, scientifically known as
Drosophila. However, the precise molecular signaling and
protein components diverged between species. In particu-
lar, in vertebrates, this process involves the primary cilium
(a specialized organelle).19,20 In outline, SHH binds to the
protein patched homolog 1 (PTCH1) receptor to remove
the inhibitory action that PTCH1 has on the transmem-
brane smoothened (SMO). Then, the activated form of SMO
initiates an intracellular signaling pathway, which inhibits
formation of GLI transcriptional repressors and stimulates
GLI transcriptional activators.19 There are three GLI pro-
teins (GLI1/2/3); however, GLI3 plays the biggest role in
anterior-posterior patterning, and its mutations result in
severe anomalies affecting the digits and brain.15,21 Although
GLI3 is expressed throughout the limb bud, the full-length
activator form (GLI3A) is present posteriorly where the SHH
concentrations are high. Contrastingly, the repressor form of
GLI3 (GLI3R) is abundant anteriorly where the SHH levels
are low. This GLI3A:GLI3R balance is what shapes the SHH
response and specifies digit number and identity.13,21,22 Null
mutations in the Shh and Gli3 alleles in mouse models result
in the development of an abnormal polydactylous paw,15 with FIGURE 3  n  The Wassel Classification.12
as many as 6–11 indefinite digits.23

CLASSIFICATION OF POLYDACTYLY
In 1995, the Congenital Hand Committee of the
International Federation of Societies for Surgery of the Hand
coined the terms radial and ulnar polydactyly, replacing the
terms preaxial and postaxial polydactyly. Radial polydactyly
refers to polydactyly that involves the thumb, whereas ulnar
polydactyly refers to polydactyly in association to the little
finger. Moreover, there is another subtype, central polydac-
tyly, which includes the ring, middle, and index fingers, and
often occurs together with syndactyly, that is, fusion of two
or more digits.

Radial Polydactyly (Preaxial Polydactyly)

Radial polydactyly is the most common form of polydac-
tyly12 and has a higher occurrence in Caucasians compared to
other ethnic populations.5 Most cases occur sporadically and
unilaterally without any association to systemic problems.24
Here, the extra digits are located anterior to the thumb as
shown in Figure 2.12
Radial polydactyly is further divided into seven subtypes
according to the Wassel Classification (Figure 3) which is a
very useful classification used by hand surgeons because it pro-
vides a structure on how to manage thumb duplication.25,26
This classification is based on an anatomic level because it
depends on the level of the skeleton at which the duplication This classification classifies polydactyly into seven types, and it is based
occurs. However, there are also some limitations because it on anatomic level, making it useful for hand surgeons.
does not provide any clue on which thumb is dominant or
if there is any indication of divergence and/or convergence
at a specific joint level.12 Divergent-convergent polydac- this classification provides no information regarding joint sta-
tyly is when the metacarpal head in Type 4 of the Wassel bility or the presence of soft tissue anomalies. Besides, tripha-
Classification is V-shaped and thus moving away while the langeal thumb is classified as Type 7 even though it might
distal portion of the extra digit comes together. Furthermore, not follow the skeletal anomalies classically described in the
Wassel Classification. 26,27 Ultimately, because this classifi-
cation is built on the assessment of the skeleton, the defect
FIGURE 2  n  Radial polydactyly.12 would not be visible in the skeletally immature newborn
under radiologic investigations. As a result, this may lead to
misdiagnosis. For example, a Type 1 duplication can be cat-
egorized as Type 2 until ossification of bones is visible.
The most common type in the Wassel Classification is
Type 4 (43 percent) followed by Type 2.28 These subtypes
are generally sporadic and unilateral. However, Type 7 can
be correlated to other conditions such as Fanconi anemia,
Diamond-Blackfan anemia, imperforate anus, Holt-Oram
syndrome, and cleft lip.

Ulnar Polydactyly (Postaxial Polydactyly)

Radial polydactyly is the most common form of polydactyly, with extra
digits anterior to the thumb.
Ulnar polydactyly often follows an autosomal dominant
pattern, with variable penetrance.5 It has a prevalence of
1 in 531 live births with a higher occurrence in the African
American population.29 In fact, it is approximately ten times
more common in African Americans than in Caucasians with a

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FIGURE 4  n  Ulnar polydactyly Types A and B.33

Type A ulnar polydactyly involves a well-developed duplicated digit that articulates with the fifth or sixth metacarpal. Type B involves a
nonfunctional rudimentary tag or a bigger pedunculated digit having a proximal skin bridge with deficient bony elements.

prevalence of 1 in 143 African American infants and 1 in 1,339
Caucasian infants. Although this duplication can be linked to an
underlying syndrome, it is usually found on its own, especially
in African Americans.30 In one study carried out by Pritsch and
colleagues,31 24 percent of patients with Type A ulnar polydac-
tyly had associated syndromes or congenital anomalies. In addi-
tion, it has an incidence of 1 in 1,000, and, in 70 percent of the
cases, it is bilateral.30
The most straightforward classification is the one pro-
posed by Temtamy and McKusick,32 where ulnar polydactyly
is divided into two types: Type A and Type B (Figure 4).
The former includes a well-developed duplicated digit that
articulates with the fifth or sixth metacarpal. In contrast,
Type B incorporates a nonfunctional rudimentary tag or a
bigger pedunculated digit having a proximal skin bridge with
deficient bony elements, and it represents up to 80 percent of
ulnar polydactyly cases.32 Thus, the latter is easier to remove
surgically. Table 1 shows a detailed description of ulnar poly-
dactyly as proposed by Rayan and Frey in 2001.33,34 This also
takes into account any small, rudimentary skin tags on the
ulnar side of the hand.
Central Polydactyly
In central polydactyly, the extra digit is located within the
middle of the hand, and it may lead to impaired motion or else
angular deformities. Usually, central polydactyly comes along
with syndactyly so that the extra finger is fused to the other.
Careful examination together with proper radiographic exam-
ination is required because the extra finger may be hidden
within the phenotype of syndactyly, that is, synpolydactyly.5
The condition of ring finger duplication together with syn-
dactyly has a particular familial propagation, and thus it can
be inherited. This has been associated to a mutation on the
HOXD13 gene on chromosome 2.35
LIMB POLARITY AND DIGIT SPECIFICATION
Attempts to determine the genetic basis of radial poly-
dactyly led to the finding of the cis-regulatory element that
controls SHH (limb-specific SHH enhancer) expression in
the posterior limb. It is called the ZPA regulatory sequence
(ZRS),22,36 located approximately 1 megabase upstream the
SHH gene, within intron 5 of the limb region 1 homologue
(LMBR1), and physically linked to SHH.11,22,37 Polydactyly
may be caused by point mutations in the ZRS.15,38,39
TABLE 1  n  Classification of Ulnar Polydactyly33,34
Type Description
I Cutaneous nubbin, which is a small lump with neither a
bony element nor a nail
II Pedunculated digit, without a movable joint or tendon but
with a bony element and small nail
III Articulating finger with the fifth metacarpal that is more
developed and with hypoplasia of the phalanx
IV Fully developed digit with the sixth metacarpal
V Ulnar polydactyly

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 Moreover, the HAND2 regulatory function is obtained
by its specific binding either to the ZRS or to HOXD13 as
an activating protein complex.40 The proteins HOXD11 to
HOXD13 are essential in controlling digit patterning, and
their inactivation contributes to polydactyly, shortening, and
dysmorphology of digits.41
Human radial polydactyly phenotype has multiple genetic
causes, but the mutation mapping to 7q36 human chromo-
some (this also has the LMBR1 gene) has an incidence of 1
in every 2,000 births. The identification of the human trans-
location t(5,7)(q11,q36) in a patient with radial polydactyly
has been crucial because this became the prime candidate for
preaxial polydactyly phenotype.17
SYNDROMES WITH POLYDACTYLY
As specified by the London Dysmorphology Data, 221
syndromes linked with polydactyly have been recorded42
when compared with Biesecker7 who listed 310 syndromes.
The most commonly encountered polydactyly syndromes are
short rib polydactyly syndromes, Greig syndrome, Cornelia
de Lange syndrome, orofaciodigital syndromes, and Bardet-
Biedl syndrome. A list of syndromes that exhibit polydactyly
is presented in Table 2. It must be taken into consideration
that, in these syndromes, one phenotype can be associated
to many genes, and one gene mutation has the potential to
cause various phenotypes.42
Polydactyly can also be induced by teratogens, thus high-
lighting its multifactorial origin. Experiments on animal
models proposed that central polydactyly can be induced
by busulfan, a chemotherapeutic agent, chemically known
as 1,4-butanediol dimethanesulfonate. This is a bifunctional
alkylating agent and highly lipophilic, thus crossing the phos-
pholipid bilayer of cells quickly.43 It is used for the treatment
of hematologic cancers including acute and chronic myeloid
leukemia because it interferes with the DNA of cancer cells,
thus inhibiting cell division by bringing about apoptosis and
cell death.44 When a dose of busulfan is given to mice embryos
at the 11th day of embryonic development, central polydac-
tyly has been observed among other digit abnormalities.45
DIAGNOSIS OF POLYDACTYLY
Polydactyly can be detected prenatally using ultrasound.
Otherwise, it is diagnosed at birth by the health care profes-
sional during the first physical examination. Once the neonate
is diagnosed with polydactyly, radiographic investigations
should be carried out, including an x-ray, to figure out any
bony elements that might be present in the extra digit of the
feet and hands. Radiology is also useful to assess for a pos-
sible underlying syndrome and to observe the remaining skel-
eton for any other possible skeletal anomalies. Furthermore,
radiology suggests what kind of surgery is required to elimi-
nate the extra digit. When this deformity is more severe and
there is involvement of bone, a pediatric orthopedic surgeon
is called to perform the procedure.46–48
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TABLE 2  n  Syndromic Polydactyly
Syndrome Associated Features
Rubinstein-Taybi Phadke and Sankar42
Smith-Lemli-Opitz Microcephaly and learning and behavioral
problems. Malformations of the lungs,
heart, GI, kidneys, and genitalia are
common. Syndactyly and polydactyly
are common (http://ghr.nlm.nih.gov/
condition/smith-lemli-opitz-syndrome).
Joubert Signs and symptoms vary. Brain
malformations are characteristic, other
organ abnormalities, polydactyly
(http://ghr.nlm.nih.gov/condition/
joubert-syndrome)
Bardet-Biedl Multisystem condition linked with obesity,
mental retardation, hypogonadism,
pigmentary retinopathy, polydactyly13
Meckel-Gruber Ulnar polydactyly, microphthalmia,
occipital encephalomeningocele, renal
dysplasia42
Greig Postaxial/preaxial polydactyly of the
cephalopolysyndactyly feet, hypertelorism, macrocephaly
with frontal bossing, syndactyly
(http://www.orpha.net/consor/cgi-bin/
OC_Exp.php?lng=EN&Expert=380.0)13,51
Pallister-Hall Head and facial malformations,
central polydactyly, hypothalamic
malformations, imperforate anus13
Above reference is made to syndromic polydactyly cases and
associated features.
Abbreviation: GI 5 gastrointestinal.
TREATMENT AND PROGNOSIS
OF POLYDACTYLY
Treatment of polydactyly varies from a simple one-day
surgical procedure to a complex one involving ligaments,
tendons, and bones. Minor cases can be corrected by tying
up the extra digit at its base, thus interrupting the flow of
blood and causing the digit to fall off.46,47
Treatment of Ulnar Polydactyly
Treatment falls into categories depending on which class
the patient presents with. In the early postnatal period,
suture ligation or excision can be carried out in the office
under local anesthesia. Formal surgical procedures together
with reconstruction can be performed at the hospital. In
Type I ulnar polydactyly, the rudimentary skin append-
age was only associated to cosmetic implications; however,
it has been recorded that, after the procedure, the lesion is
extremely sensitive because of the formation of a neuroma.
The neuroma develops because, beneath suture ligation,
the digital nerves of the rudimentary digit are cut off at the
level of the skin, so they cannot retract in the soft tissues.33
Consequently, the infant is prone to abrade the skin tag,
causing skin breakdown.
For Type II, treatment also involves suture ligation, which
induces necrosis of the distal segment, accompanied by
autoamputation approximately 10–20 days later. However,
because of complications, it is often corrected in the oper-
ating suite under formal surgical techniques. This is similar
to the treatment for Types III–V. Often, the latter requires
reconstruction of the surrounding soft tissue and ablation of
the extremity.33
Treatment of Radial Polydactyly
Surgical treatment for radial polydactyly depends on
the Wassel Classification (Table 3). Type I can be cor-
rected by the Bilhaut-Cloquet separation because the
length of the thumb is often the same. It involves removal
of excess skin, nail, and bone within the central portion of
the duplicated thumb. This procedure creates many prob-
lems such as unintentional epiphysiodesis (i.e., premature
fusion of the epiphysis and the diaphysis, leading to ces-
sation of growth) and residual nail deformities, which can
be eradicated by the removal of the nail from one of either
thumbs. Type II makes the choice easier because of the
size, function, deviation, and passive mobilization of the
extra thumb, but, when both thumbs are similar, the deci-
sion depends on the nerve and tendon anatomy.49 This is
necessary to assess the insertions of the extensor and flexor
tendons and to evaluate the collateral ligaments’ strength.
Also, the Bilhaut-Cloquet separation technique can be
performed. For Type III, the surgeon can be neutral about
which thumb is eliminated, depending on the aesthetic-
functional evaluation.49
TABLE 3  n  Radial Polydactyly Treatment49
Type as Defined by the
Wassel Classification Surgical Treatment
Type I Bilhaut-Cloquet separation is the removal
of excess skin, nail, and bone within
the central portion of the duplicated
thumb.
Type II Bilhaut-Cloquet separation
Type III Surgical removal of the extra digit
in Type III depends on aesthetic-
functional evaluation.
Type IV The ulnar thumb is preferred during
the surgical procedure because this
removes the ulnar collateral ligament,
which is fundamental for thumb
stabilization.
Type V Here, surgery is identical to that of
Type IV with prime attention given to
conserve the ulnar thumb.
Type VI The ulnar thumb requires precise
reinsertion of the radial collateral
ligament of the metacarpal-trapezoidal
joint to be conserved properly,
together with the abductor brevis
muscle.
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Glossary
Allele—This is a variant form of a gene.
Epiphysiodesis—This is the premature fusion of the
epiphysis and the diaphysis, leading to cessation of growth.
Lateral plate mesoderm—This is mesoderm-derived
tissue that divides into the visceral and somatic layers
surrounding the organs and body cavity.
Limb primordium—This is the very first indication
of the developing limbs in the embryo. It consists of a
mesenchymal core originating from the somatic layer of
the lateral plate mesoderm and is covered by ectoderm.
The lateral plate mesoderm forms the bones and
connective tissue of the limbs.
Somatopleure—This is an embryonic layer formed by
the association of the ectoderm and somatic layers of the
lateral plate mesoderm.
In Type IV, the ulnar thumb is preferred during the surgi-
cal procedure because this removes the ulnar collateral liga-
ment, which is fundamental for thumb stabilization. Here,
proper realignment of the extensors and flexors is important
primarily in divergent-convergent polydactyly. Furthermore,
removal of the duplicated head and regularization of the
metacarpal diaphysis and head is vital to reduce intolerable
postoperative outcomes. Also, for proper reconstruction of
the collateral ligament, it needs to be preserved between the
two identical phalanges, that is, the one in the middle of the
metacarpal and dismissed phalanx.49 Once the first web space
is constricted, the skin of the identical thumb to be elimi-
nated is saved. For Type V, the surgery is identical to Type
IV, with prime attention given to conserve the ulnar thumb.
In Type VI, the ulnar thumb requires precise reinsertion of
the radial collateral ligament of the metacarpal-trapezoidal
joint to be conserved properly, together with the abductor
brevis muscle. Ultimately, the extra phalanx in Type VII is
eliminated, and the soft tissues are reconstructed.
CONCLUSION
Because polydactyly is a common congenital anomaly, it is
necessary for the health care professional to have knowledge
of it and to understand the various scenarios in which it can
present. Although it can present simply as a cosmetic defect,
which can be corrected surgically, it can also be a complex with
other anomalies. Thus, it is important for the health care pro-
fessional to discuss with the parents to be their family history
and to educate them about all the possible outcomes for their
newly diagnosed baby. In addition, the necessary investigations
should be carried out so as not to miss any underlying syndrome
and to make sure the proper surgical treatment is chosen.
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51. Hui CC, Joyner AL. A mouse model of Greig cephalo-polysyndactyly Neonatal Nurse Practitioner sought for 24-bed
syndrome: the extra-toesJ mutation contains an intragenic deletion of the
Gli3 gene. Nat Genet. 1993;3(3):241-246.
Level 3 NICU at Howard County General Hospital
(a member of Johns Hopkins Medicine), a progressive
About the Authors community hospital. Baltimore-Washington corridor.
Marie Claire Farrugia is a medical student in her final year of Seeking highly motivated experienced CNNP—team-
studies, and she has carried out research projects on limb congenital oriented, excellent interpersonal skills, takes initia-
abnormalities under the supervision of Jean Calleja-Agius. tive, and committed to quality patient care. Deliveries
Jean Calleja-Agius, MD, MRCOG, MRCPI, MSc, PhD, is cur- 3,5001. HFOV, active Perinatal Center. Full-time days
rently the head of the Department of Anatomy, Faculty of Medicine (with some possible nights and weekends). Immediate
and Surgery at the University of Malta. She is responsible for teaching opening. Competitive salary and benefits. Beautiful
embryology and reproductive sciences to undergraduate medical and suburban community 25 minutes from Baltimore and
allied health care professionals.
about 45 minutes from Washington, D.C.
For further information, please contact:
Jean Calleja-Agius, MD, MRCOG, MRCPI, MSc Clinical Interested candidates should contact
Embryology (Leeds), PhD (London) Tuvia Blechman, M.D. at 410-740-7557
University of Malta or e-mail CV to gblechman@jhmi.edu
Department of Anatomy EOE/AA
MSD 2090 Malta
E-mail: jean.calleja-agius@um.edu.mt

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