Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 391 - файл
.pdf
3 Hand Defects: AnIsolated Anomaly Or a Syndromic Disease?
https://t.me/medicina_free
33
occurs when the inner membrane (amnion) ruptures without injury to the outer membrane (chorion), this exposes the baby to brous sticky
tissue (bands) from the ruptured amnion which
can oat in the water of the uterus; these brous
tissues can entangle the baby, reducing blood
supply and causing congenital abnormalities. In
some cases, a complete “natural” amputation of a
digit(s) or limb may occur before birth or the
digit(s) or limbs may be necrotic and require surgical amputation following birth. No genetic test
is indicated or required, because the diagnosis
can be simply done by clinical evaluation. This a
classical nongenetic condition in which the prognosis of the newborn regarding growth and psychomotor development is absolutely normal.
Because of its environmental origin, the recurrence risk for the parents and for the child himself is not increased in comparison with general
population [4].
3.4.2 Poland Syndrome
Poland syndrome has an incidence of 1/20–
30,000 live births. Clinical diagnosis is made in
neonatal period or later in patient with an asymmetrical hypoplasia of pectoral muscles with
possible involvement of the rib cage, associated
with ipsilateral anomalies of the upper limb;
more rarely the limb involvement can be bilateral. In particular limb, anomalies can be variable
and can be characterized by shortness of ngers,
syndactyly of hypoplastic ngers, global hypoplasia of the hand and of the forearm. Both
growth and psychomotor development are usually normal. Up to now, no molecular anomaly
has been discovered as a cause of Poland syndrome whose diagnosis is still only clinically
based [5].
3.4.3 Acrocephalosyndactylies
Acrocephalosyndactyly syndromes represent a
group of inherited congenital malformation disorders characterized by craniosynostosis and
fusion or webbing of the ngers or toes, often
with other associated manifestations. Most of
these conditions are due to the mutation of
FGFRs’ genes. The condition whose clinical
diagnosis is easier is Apert syndrome. The
patients affected with this disease show craniosynostosis frequently of the coronal sutures giving a acro-brachycephalic shape of the cranium.
The facial features are inuenced by the cranium
anomalies. In particular, eyes are prominent due
to shallow orbits, midface is at, palate is high
and arched, mandible is relatively prominent.
The hands and feets show skin and osseus fusion
that involves at minimum the second, third, and
fourth ray but it can involve all the ngers. The
patients have a growth in the lower part of normal
curves. They can have some delays in psychomotor development; mean IQ is 70 with a range
between 50 and 90. The children can manifest
nutritional, respiratory and neurosurgery complications that should actively monitored and
treated. The genetic defect is represented by
autosomal dominant mutation of FGFR2 gene
[6].
Pfeiffer syndrome is another common disease
belonging to this group. The core anomaly is
localized to the hands and feet in which thumbs
and hallux are large and medially deviated and in
which is evident skin syndactyly involving 2°–3°
ngers and toes (less frequently 3° and 4°).
According to the presence/severity of craniosynostosis are known three different subtypes: type 1
with mild expression, good prognosis, and normal intellectual development, type 2 with a more
severe involvement, severe craniosynostosis and
worse prognosis and type 3 quite similar to type
2, without evidence of clover leaf skull. Mutation
of FRGFR1 (exon7) and FGFR2 (exons 8 and
10) are the biological markers of the disease [7].
Saethre–Chotzen syndrome is another disease
of this group in which hand and feet anomalies
are evident. In particular, patients affected have
brachydactyly, because of shortness of terminal
phalanges and partial skin syndactyly of 2–3° ngers less frequently 3–4°. Thumbs can be triphalangeal. The feet hallux is large and it’s possible
to see skin syndactyly of toes. Together with
these anomalies, the patients show facial dysmorphisms with asymmetric face, ptosis, strabismus,
34
https://t.me/medicina_free
A. Selicorni et al.
downslanting of palpebral ssures, hypertelorism, hypoplastic maxilla, high arched palate,
and peculiar ears. Craniosynostosis is not constantly present and can involve different sutures
with variable severity. Physical growth and intellectual development are usually normal except
for patients with chromosomal microdeletions
that can show intellectual disability. Genetic
defect involves autosomal dominant mutation or
microdeletion of the TWIST gene on chromosome 7p21 [8].
Another common disease of this group is
Crouzon syndrome in which classically no hands
and feet anomalies are present.
3.4.4 Arthrogryposis Multiplex
Congenita
Arthrogryposis multiplex congenital is a large
and heterogeneous group of disorders characterized by congenital limb contractures. It manifests as a limitation of movement of multiple
limb joints at birth that is usually nonprogressive
and may include muscle weakness and brosis.
Typically mothers of these children describe
decreased intrauterine fetal movement which
leads secondarily to the contractures. The
reduced movements can have a neurologic basis
(cerebral, spinal, or peripheral nerves involvement) a muscular basis (myasthenia gravis, muscular dystrophies, and mitochondrial diseases)
or a connectival basis; a reduce intrauterine
space can be responsible too. The incidence of
the syndromes with multiple contractures is
about 1/3000 live births. It’s easy to understand
that it would be very long and complex to go into
details in this large chapter. Within this group,
we identify a subgroup named distal arthrogryposis and in this category, we want to put our
attention to one syndrome whose phenotype is
so typical to be recognized at birth. This is the
case of Freeman–Sheldon syndrome in which the
newborns show joints’ contractures as typical for
distal arthrogryposis, associated with contractures of facial muscles causing a very little
mouth (whistling face). In the skin under the
mouth is classically evident an “H shape” skin
fold. This combination of facial features is absolutely specic for this disease and permits a
gestaltic diagnosis. Usually, the psychomotor
development of these children is pretty normal
while weight growth can be slow because of
nutritional difculties. Autosomal dominant
mutations of MYH3 gene are responsible of
about 90% of the cases [9].
3.4.5 Bardet–Biedl Syndrome
Bardet–Biedl is a genetic syndrome characterized by the association between obesity, retinal
dystrophy, polydactyly, genital anomaly, hypogonadism, and renal defects.
Its prevalence is about 1/100,000–1/160,000
live births. The clinical diagnosis is made if a
proper combination of primary (major) and
secondary (minor) criteria are present: primary
features are retinal dystrophy, polydactyly,
obesity, learning disability, hypogonadism,
renal and urinal tract anomalies. Secondary
criteria are the following: language delay, ocular anomalies like cataracts strabismus, brachydactyly or syndactyly, ataxia, mild spasticity in
particular at lower limbs, diabetes, hepatic
brosis, and heart problems. Clinical diagnosis
is possible when a patient shows four major
criteria or three major criteria and two minors.
As regards hand polydactyly is often the rst
manifestation evident at birth. Usually is a
postaxial polydactyly and is evident in70–80%
of the cases. The variability is wide; from one
extremity to all four can be involved. The last
chance regards about 21% of patients. Feet are
more frequently interested. Apart from psychomotor problems, patients with Bardet Biedl
syndrome can evolve toward severe impairment of visual ability from the age of 15.
Usually, rst visual symptoms can be evident
from 6 to 8years of age. The syndrome has an
autosomal recessive inheritance and about 20
different genes can be involved, so molecular
conrmation of a clinical diagnosis is hardworking and not always possible [10].
3 Hand Defects: AnIsolated Anomaly Or a Syndromic Disease?
https://t.me/medicina_free
35
3.4.6 Fanconi Anemia
The disease is characterized by the association of
progressive bone marrow insufciency, increased
risks of development of neoplasia, congenital
defects and extreme toxicity to exposure to radiations and chemotherapy drugs. Its incidence is
about 1/160,000. Between the various possible
congenital defects, 50% of the patients have skeletal anomalies whose 70% involve upper limbs.
In particular, the thumbs can be absent, little,
bid or triphalangeal. The radius can be short of
absent too and, in this case, ulna is short and
arched. The stature is short while psychomotor
development can be delayed. As we have
reported, there is an increased risk of hematologic and non-hematologic neoplasias. This
means that patients need to be followed properly
in order to early diagnose possible tumors. The
syndrome has a genetic basis and an autosomal
recessive etiology. That means that recurrence
risk is 25% for an healthy couple of parents of an
affected child. About 19 genes have been related
to the syndrome. A screening test is represented
by cytogenetic analysis with DEB exposure in
order to show an increased chromosomal fragility [11].
3.4.8 VATER/VACTERL Association
VATER association is a complex malformative
condition characterized by a particular spectrum
of anomalies including: vertebral defect, imperforate anus, tracheo-esophageal stula, esophageal atresia and renal/radial dysplasia. Later, the
observation of a high frequency of cardiac and
limb anomalies in these patients permitted to
modify the original acronym from VATER to
VACTERL. Its prevalence is between 1/20,000
and 1/40,000 newborns As regard limb anomalies, they are present in 40–50% of the affected
individuals. The most common defects are the
following: radial hypo/aplasia, thumb hypo/aplasia preaxial polydactyly. VATER’s patients grow
normally and have a normal achievement of the
common psychomotor milestones. Up to now, no
specic genetic defect has been discovered as
associated with the disease whose diagnosis is
still now only clinical. No formally dened clinical criteria are available. Hall suggested that clinical diagnosis can be acceptable if the patient has
an anomaly in all three regions of the body
(limbs, thorax, and inferior abdominal region/
pelvis). Other authors believe that esophageal
and anal defects are mandatory in order to consider this diagnosis [13].
3.4.7 Holt–Oram Syndrome
Holt–Oram is a rare syndrome characterized by
the association of preaxial limb defect and heart
anomalies. Its prevalence is 1/100,000 newborns.
At upper limb, it’s possible to diagnose various
types of malformations: absent thumbs, triphalangeal thumbs, phocomelia, radial hypo/aplasia,
carpal bone anomalies, abnormal elbow movements, possible anomalies at clavicles and scapula. In total, 75% of patients have heart problems;
60% of them show an interatrial defect, 30%
have interventricular muscular defect. Other
heart malformations have been described. In
total, 40% of patients have an ECG anomaly also
in absence of a cardiac malformation. Growth
and psychomotor development are usually normal. In total, 70% of affected children show autosomal dominant mutation of TBX5 gene [12].
3.4.9 Oro-Facio-Digital Syndromes
Oro-facio-digital syndromes refer to numerous
conditions in which major or minor anomalies
can be evident at the oral cavity (mouth, tongue,
teeth, and jaw), facial structures (head, eyes, and
nose), and digits (ngers and toes). Association
with major problems in different organs or apparatus are described. The literature reports up to 17
types of oro-facio-digital syndrome, but research
is necessary to conrm and clarify all of these
types. Hands involvement is usually characterized by brachydactyly, syndactyly, or preaxial
polydactyly. The prognosis and the severity of
the disease are very variable between different
types. For most of them the exact genetic basis of
the condition is unknown; the pattern of inheritance is different in the various subtypes [14].
36
https://t.me/medicina_free
A. Selicorni et al.
3.4.10 Cornelia de Lange Syndrome
Cornelia de Lange syndrome, or as recently stated
Cornelia de Lange spectrum, refers to a phenotype
characterized by quite typical facial dysmorphisms, hirsutism, intrauterine and postnatal
growth retardation, psychomotor delay, and intellectual disability of different severity. The prevalence of the condition is from 1/10,000 to 1/30000
live births. About 1/3 of patients can show limb
malformation mostly at upper limb. The defect is
quite variable and can splurge from severe limb
reduction anomalies toward the absence of various
ngers typically of ulnar side. Some patients can
show a combination of reduction defects in one
hand and postaxial polydactyly in the contralateral
hand. Genetic basis is very complex and heterogeneous and refers to possible mutations in genes of
the cohesion complex. However, it’s important to
state that patients with major limb involvement
usually show mutation in only one gene (NIPBL)
which is responsible for about 60–65% of the
genetic defects and correlates with the more classical phenotype. It should be remembered that in a
signicant amount of patients, also with a quite
classical phenotype, the molecular defects cannot
be evidenced on blood lymphocyte but it’s necessary to test another tissue (usually cells obtained
from oral mucosa brush). This phenomenon is
named somatic mosaicism [15].
3.4.11 Rubinstein–Taybi Syndrome
Rubinstein–Taybi syndrome is characterized by
the association of typical facial dysmorphisms,
psychomotor delay/intellectual disability, and
peculiar shape of thumbs and hallux. Its prevalence at birth is 1/100,000–1/125,000. The eyes
and nasal region are the hallmarks of this condition regards facial dysmorphisms. Thumbs and
halluxs are classically large and in 1/3 of patients
deviated (varism or valgism). Sometimes they
can be also bid or duplicated (preaxial polydactyly). Occasionally, a postaxial polydactyly of
feet can be observed.
As stated, patients with Rubinstein Taybi syn-
drome have a variable degree of intellectual dis-
ability; growth can be reduced, especially in the
rst years of life, also if some of these children
can evolve toward overweight/obesity in preadolescent/adolescent age. The genetic basis of the
syndrome is heterogeneous. Some patients can
show a microdeletion of the short arm of chromosome 16 (16p11.2), the majority has an autosomal dominant mutation in CREBP gene (localized
in the 16p11.2 region) and lastly a minority of
individuals have an autosomal dominant mutation of EP300 gene. Somatic mosaicism has been
observed in Rubinstein Taybi patients too [16].
3.4.12 Smith–Lemli–Opitz Syndrome
Smith–Lemli–Opitz syndrome is a disease of
cholesterol metabolism associated with multiple
congenital anomalies caused by a deciency of
7-dehydro-cholesterol reductase enzyme (7DHC)
which is important into conversion of 7DHC to
cholesterol. Its prevalence is 1/20,000–1/40,000
live births. The main clinical problems are facial
dysmorphisms, prenatal and postnatal growth
retardation, microcephaly, psychomotor retardation and intellectual disability of moderate severe
degree and multiple malformations (cleft palate,
heart anomalies, central nervous system defects,
ambiguous genitalia hypoplastic penis, and hypospadias). At the extremities, postaxial polydactyly and peculiar 2–3° toes syndactyly (Y shaped)
are evident. Clinical hypothesis can be conrmed
with the dosage of serum 7DHC or 8DHC which
are abnormally high in front of a cholesterol concentration quite low. Molecular study of the gene
coding for the defective enzyme is another way to
conrm the diagnosis. The disease has an autosomal recessive pattern of inheritance, so diagnosis
is extremely important for a proper genetic counseling for further pregnancies [17].
3.4.13 Greig Syndrome
Greig cephalopolysyndactyly syndrome is characterized by macrocephaly, preaxial polydactyly or mixed pre- and postaxial polydactyly,
and widely spaced eyes. Mildly affected patients
3 Hand Defects: AnIsolated Anomaly Or a Syndromic Disease?
https://t.me/medicina_free
37
may have subtle craniofacial ndings. Greig
syndrome is part of a clinical spectrum whose
mild spectrum is represented by preaxial polysyndactyly type IV and crossed polydactyly
(preaxial polydactyly of the feet and postaxial
polydactyly of the hands plus syndactyly of ngers 3–4 and toes 1–3). Individuals with classical form can have seizures, hydrocephalus, and
intellectual disability, but this covers only 10%
of patients. The diagnosis of Greig syndrome is
based on clinical ndings and family history.
The molecular basis of the disease is represented by GLI3 gene anomalies. They can be a
deletion involving GLI3 gene (7p14.1 region) or
a pathogenetic dominant mutation of the gene
sequence itself. The detection rate of genetic
tests is about 75% [18].
3.4.14 EEC Syndrome
EEC syndrome is an acronym for EctrodactylyEctodermal Dysplasia-Cleft Lip/Palate. It is a
rare form of ectodermal dysplasia. The symptoms can be variable and most commonly refers
to hand/feet malformation (ectrodactyly or split
hand/foot malformation), ectodermal dysplasia
symptoms (with hair and glands anomalies), and
cleft lip and/or palate. Other frequent features are
distinctive facial features, eyes and urinary tract
anomalies EEC syndrome is inherited with an
autosomal dominant pattern. More than 90% of
individuals have mutations in the TP63 gene
(EEC type 3). Other individuals with EEC syndrome are thought to have a mutation in a region
on chromosome 7 (EEC1) [19].
3.5 Dierential Diagnosis
According Types ofHand
Defect
Table 3.3 Syndromes with preaxial polydactyly
Biemond syndrome
Brachio–Oculo facial syndrome
Cranio Fronto nasal dysplasia
Fanconi anemia
Fetal-alcohol syndrome
Goltz syndrome
Greig syndrome
Hydrocephalus syndrome
Jeune syndrome
Kaufmann–Mckusick syndrome
Larsen syndrome
Meckel–Gruber syndrome
Nager syndrome
Oro-facio-digital syndrome
Short rib polydactyly syndrome
Robinow syndrome
VATER association
Table 3.4 Syndromes associated with postaxial
polydactyly
Acro-callosal syndrome
Acrocephalopolysyndactyly
Bardet–Biedl syndrome
Biemond syndrome
Carpenter syndrome
Craniofrontonasal dysplasia
Ellis–Van Creveld syndrome
Fetal–Valproate syndrome
Goltz syndrome
Greig syndrome
Holt–Oram syndrome
Hydrolethalus syndrome
Jeune syndrome
Joubert syndrome
Kaufman–Mckusick syndrome
Pallister–Killian syndrome
Maternal diabetes syndrome
Orofaciodigital syndromes
Pallister–Hall syndrome
Schinzel–Giedion syndrome
Short rib polydactyly syndrome
Simpson–Golabi–Behmel syndrome
Smith–Lemli–Opitz syndrome
Young–Simpson syndrome
In Tables 3.3, 3.4, 3.5, 3.6, and 3.7 we summarize
the main syndromes that should be considered in
differential diagnosis in front of a particular
major anomaly of the hands. Of course, the lists
are not exhaustive but can be useful for a rst
approach. As it’s well known it’s now possible to
use databases of free access (Orphanet) or affordable (Oxford Medical database, POSSUM) that
can help clinicians to generate a list of possible
diagnosis starting from clinical features (major
and minor) of the patient [20].
38
https://t.me/medicina_free
A. Selicorni et al.
Table 3.6 Syndromes associated with absent/hypoplastic thumb
Aase syndrome
Acrorenal syndrome
Brachio-oculo-facial syndrome
Fanconi anemia
Feingold syndrome
Fetal alcohol syndrome
Holt–Oram syndrome
LADD syndrome
Lenz syndrome
Maternal diabetes syndrome
Nager syndrome
Rothmund–Thompsen syndrome
Smith–Lemli–Opitz syndrome
VATER association
Yunis–Varon syndrome
Table 3.5 Syndromes associated mesoaxial polydactyly
Ellis–van Creveld syndrome
Holt–Oram syndrome
Kaufman–Mckusick syndrome
Orofaciodigital syndromes
Robinow syndrome
Pallister–Hall syndrome
Table 3.7 Syndromes associated with triphalangeal
thumb
Aase syndrome
Fanconi anemia
Fetal hydantoin syndrome
Holt–Oram syndrome
LADD syndrome
Nager syndrome
Townes syndrome
3.5.1 The New Genetic Tests
andTheir Use
intheDiagnostic Process
Genetic tests are changing, increasing the possibility of testing and modifying the approach to
the diagnosis. Up to 10years ago, the geneticist
had few opportunities to use genetic tests to conrm a clinical diagnosis. It was possible to evaluate the number of chromosomes and their general
structure with the possibility of detecting deletion or duplication with 5–10 Mb of size. The
next step was the discovery of molecular cytoge-
netic with FISH (uorescent in situ hybridization) study. Thank to this approach, there was the
possibility of showing more little deletions/duplications in specically related chromosomal
regions to conrm the suspicion of dened syndromes or, later on, to search for abnormalities in
the terminal part of chromosomes (telomeres) in
very complex children with a so-called “chromosomal phenotype.” At gene level, it was growing
the availability of tests able to identify mutation
in single gene considered to be the cause of specic disease [21].
The rst revolution was related to the introduction in clinical practice of the array CGH
technology. Thank to this new approach, completely different from cytogenetics from a methodological point of view, it has become possible
to detect deletion or duplication of very low size
(hundreds of bases instead of millions of bases)
extremely increasing the number of patients in
whom an abnormality has been detected. This
technology has now taken the place of the old
standard karyotype as rst-level cytogenetic
approach. The side effect of array CGH implementation is the discovery of a great number of
variants (both deletion or duplication) which are
absolutely benign or for which is not possible to
dene for sure the real meaning (named
VOUS=variant of unknown signicance). This
means that the correct interpretation of the results
of an arrayCGH study needs a specic and very
specialist competence [21].
At molecular level during the last few years, it
has become clear that genetic basis of the great
majority of the genetic syndromes is highly heterogeneous. For a lot of syndromes in fact, the
number of genes, whose mutations were related
to that phenotype, has been increasing months
after months. This situation created difculty in
performing complete molecular study of patients
suspected to be affected by a highly heterogeneous disease. The last revolution was so related
to the introduction of a new approach in sequencing technology named NGS (next-generation
sequencing) [21]. Thank to this approach it was
possible to study at the same time hundreds and
hundreds of genes selecting their really important
3 Hand Defects: AnIsolated Anomaly Or a Syndromic Disease?
https://t.me/medicina_free
39
part: the exons, the coding part of every gene. In
this way, we are able to study in a single experiment all the genes related to a specic syndrome,
all the known genes related to a specic problem
(the so-called genetic panels), all the exons of the
known genes (named clinical exome) all the
exons of our genome (WES = Whole exome
sequencing) [22]. Table 3.8 summarizes these
denitions. Thank to this new approach the time
necessary to study at the molecular level a single
patient greatly decreased. In addition, this
approach has improved tremendously the possibility to reach a diagnosis in very complex children affected by the so-called “ultra rare
diseases”; a lot of papers describing the analysis
Table 3.8 the new various possibility available thank to
NGS technology
Genetic
panels
Clinical
exome
Whole-exome
sequencing
Wholegenome
sequencing
Analysis of the exons of all the genes
related to an heterogeneous syndrome
(e.g. Bardet–Biedl syndrome) or related
to a specic clinical problem (epilepsy)
Analysis of the exons of all the known
genes
Analysis of all the exons of our genome
Analysis of all the exons and introns of
our genome
of different cohorts of patients report a detection
rate from 30% to 50%. Moreover, this technology
demonstrated to be very cost-effective. Economic
studies showed that the cost of this new analysis
is absolutely lower than that of the various single
genetic tests performed by patients without having a signicant result [23, 24].
For this reason, some authors suggested a new
methodological approach to the child with multiple congenital defects which is shown in
Fig.3.2. If the clinician has a reasonable clinical
hypothesis, it’s important to search the conrmation with usual genetic tests. If a good hypothesis
is lacking, it’s better to use the new technology
(array CGH and WES in sequence) instead of
wasting time in performing genetic tests with few
possibilities to reach the goal. As for array CGH,
the more we know the more we can have doubts.
Also a WES study can generate results with
unknown or hardly interpretable meaning; for
this reason, this kind of tests need to be managed
by expert geneticists [25–27].
What is important to understand is that with
this approach, the physician’s role is no less
important than in the past. A very deep and
detailed clinical analysis is extremely important
in order to accurately dene the phenotype of the
patient and in order to compare it with the pheno-
- Phenotypesuggesve
for a specific clinical
diagnosis (gestalt
diagnosis)
TARGETED TESTING:
-Single gene
- Genec panel
-Methylaon test
-FISH study
-Karyotype
Fig. 3.2 New methodological approach to a child with multiple congenital defects
neg
Clinical genec evaluaon
-Reviewrecords/family and perosnal
history
-Physicalexaminaon
-Searchfor associatedanomalies
-Complex phenotype not
suggesve for a specific
diagnosis
- Genecdisorder higly
heterogeneousor for which
no genecdefecthas been
defined
Chromosome
microarray
NGS
-Clinicalpresentaon not
consistent with a
genec disorder
Clinicalfollow-up
40
https://t.me/medicina_free
A. Selicorni et al.
type of patients which show a specic genetic
defect. Whereas in the past the clinician’s task
was only to suggest a possible clinical diagnosis
and seek the conrmation with genetic testing,
the new technology has added a new role: to conrm that a specic genotype suggested by arrayCGH or WES may be the correct explanation for
the patient’s phenotype.
References
1. Rasmussen SA, Olney RS, Holmes LB, Lin AE,
Keppler-Noreuil KM, Moore CA, National Birth
Defects Prevention Study. Guidelines for case classication for the National Birth Defects Prevention
Study. Birth Defects Res A Clin Mol Teratol.
2003;67:193–201.
2. Solomon BD, Muenke M.When to suspect a genetic
syndrome. Am Fam Physician. 2012;86:826–33.
3. Dy CJ, Swarup I, Daluiski A.Embryology, diagnosis,
and evaluation of congenital hand anomalies. Curr
Rev Musculoskelet Med. 2014;7:60–7.
4. Durga R, Renukadevi TK. Amniotic band syndrome – a dreaded condition. J Clin Diagn Res.
2016;10:QD04–5.
5. Moir CR, Johnson CH. Poland’s syndrome. Semin
Pediatr Surg. 2008;17:161–6.
6. Kumar GR, Jyothsna M, Ahmed SB, Sree Lakshmi
KR. Apert’s Syndrome. Int J Clin Pediatr Dent.
2014;7:69–72.
7. Vogels A, Fryns JP. Pfeiffer syndrome. Orphanet J
Rare Dis. 2006;1:19.
8. Kress W, Schropp C, Lieb G, Petersen B, BüsseRatzka M, Kunz J, Reinhart E, Schäfer WD, Sold J,
Hoppe F, Pahnke J, Trusen A, Sörensen N, Krauss J,
Collmann H. Saethre-Chotzen syndrome caused by
TWIST 1 gene mutations: functional differentiation
from Muenke coronal synostosis syndrome. Eur J
Hum Genet. 2006;14:39–48.
9. Gurjar V, Parushetti A, Gurjar M.Freeman-sheldon
syndrome presenting with microstomia: a case
report and literature review. J Maxillofac Oral Surg.
2013;12(4):395–9.
10. Forsythe E, Beales PL.Bardet-Biedl syndrome. Eur J
Hum Genet. 2013;21(1):8–13.
11. Mehta PA, Tolar J.Fanconi anemia. [updated 2018].
GeneReviews® [Internet]. Seattle, WA: University of
Washington, Seattle; 2002. p.1993–2018.
12. Krauser AF, Schury MP. Holt Oram syndrome
StatPearls [Internet]. Treasure Island, FL: StatPearls
Publishing; 2018.
13. Chen Y, Liu Z, Chen J, Zuo Y, Liu S, Chen W, Liu
G, Qiu G, Giampietro PF, Wu N, Wu Z.The genetic
landscape and clinical implications of vertebral
anomalies in VACTERL association. J Med Genet.
2016;53:431–7.
14. Dave KV, Patel SC, Dudhia BB, Panja P.Orofacial digital syndrome. Indian J Dent Res. 2013;24(1):132–5.
15. Kline AD, Moss JF, Selicorni A, Bisgaard AM,
Deardorff MA, Gillett PM, Ishman SL, Kerr LM,
Levin AV, Mulder PA, Ramos FJ, Wierzba J, Ajmone
PF, Axtell D, Blagowidow N, Cereda A, Costantino A,
Cormier-Daire V, FitzPatrick D, Grados M, Groves L,
Guthrie W, Huisman S, Kaiser FJ, Koekkoek G, Levis
M, Mariani M, McCleery JP, Menke LA, Metrena
A, O’Connor J, Oliver C, Pie J, Piening S, Potter
CJ, Quaglio AL, Redeker E, Richman D, Rigamonti
C, Shi A, Tümer Z, Van Balkom IDC, Hennekam
RC.Diagnosis and management of Cornelia de Lange
syndrome: rst international consensus statement.
Nat Rev Genet. 2018;19:649.
16. Hennekam RC. Rubinstein-Taybi syndrome. Eur J
Hum Genet. 2009;14(9):981–5.
17. Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz
syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet.
2012;160C(4):250–62.
18. Biesecker LG.The Greig cephalopolysyndactyly syndrome. Orphanet J Rare Dis. 2008;24:3–10.
19. Okamoto N. Ectodactyly-ectodermal dysplasiaclefting syndrome. Ryoikibetsu Shokogun Shirizu.
2001;33:615–7.
20. Ahmed H, Akbari H, Emami A, Akbari MR.Genetic
overview of syndactyly and polydactyly. Plast
Reconstr Surg Glob Open. 2017;5(11):e1549.
21. Durmaz AA, Karaca E, Demkow U, Toruner G,
Schoumans J, Cogulu O. Evolution of genetic techniques: past, present, and beyond. Biomed Res Int.
2015;2015:461524.
22. Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S,
Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw
M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA,
Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody
WW, Vilain E, Nelson SF.Clinical exome sequencing
for genetic identication of rare Mendelian disorders.
JAMA. 2014;312:1880–7.
23. Valencia CA, Husami A, Holle J, Johnson JA, Qian
Y, Mathur A, Wei C, Indugula SR, Zou F, Meng H,
Wang L, Li X, Fisher R, Tan T, Hogart Begtrup A,
Collins K, Wusik KA, Neilson D, Burrow T, Schorry
E, Hopkin R, Keddache M, Harley JB, Kaufman KM,
Zhang K. Clinical impact and cost-effectiveness of
whole- exome sequencing as a diagnostic tool: a pediatric center’s experience. Front Pediatr. 2015;3:67.
24. Monroe GR, Frederix GW, Savelberg SM, de Vries TI,
Duran KJ, van der Smagt JJ, Terhal PA, van Hasselt
P, Kroes HY, Verhoeven-Duif NM, Nijman IJ, Carbo
EC, van Gassen KL, Knoers NV, Hövels AM, van
Haelst MM, Visser G, van Haaften G.Effectiveness of
whole-exome sequencing and costs of the traditional
diagnostic trajectory in children with intellectual disability. Genet Med. 2016;18:949–56.
3 Hand Defects: AnIsolated Anomaly Or a Syndromic Disease?
https://t.me/medicina_free
41
25. Stark Z, Tan TY, Chong B, Brett GR, Yap P, Walsh
M, Yeung A, Peters H, Mordaunt D, Cowie S, Amor
DJ, Savarirayan R, McGillivray G, Downie L, Ekert
PG, Theda C, James PA, Yaplito-Lee J, Ryan MM,
Leventer RJ, Creed E, Macciocca I, Bell KM, Oshlack
A, Sadedin S, Georgeson P, Anderson C, Thorne
N, Melbourne Genomics Health Alliance, Gaff C,
White SM.A prospective evaluation of whole-exome
sequencing as a rst-tier molecular test in infants
with suspected monogenic disorders. Genet Med.
2016;18:1090–6.
26. Levenson D.Whole-exome sequencing strategy proposed as rst-line test. Am J Med Genet. 2016:1387–8.
27. Thevenon J, Duffourd Y, Masurel-Paulet A.Diagnostic
odyssey in severe neurodevelopmental disorders:
toward clinical whole-exome sequencing as a rstline diagnostic test. Clin Genet. 2016;89:700–7.
Paediatric Trigger Finger
https://t.me/medicina_free
ChiaraNovelli andGiorgioPajardi
4
Abstract
Paediatric trigger thumb and trigger nger
represent distinct conditions and should not
be treated like adult-acquired trigger nger.
Paediatric trigger thumb presents not at birth
but early in childhood. Recently, our understanding of the pathophysiology of paediatric
trigger thumb and paediatric trigger nger
has improved leading to a better understanding of the problem and of its treatment.
Paediatric trigger thumb may spontaneously
resolve with splint, although in several years.
Open surgical release of the A1 pulley of the
thumb is an alternative option that nearly
uniformly restores thumb interphalangeal
joint motion. Paediatric trigger nger usually
requires surgical approach; isolated release
of the A1 pulley has been associated with
high recurrence rates. Awareness of the anatomic factors that may contribute to triggering in the paediatric nger and willingness to
explore and address other involved components of the exor mechanism can prevent
surgical failure.
C. Novelli (*) ∙ G. Pajardi
Department of Hand Surgery and Rehabilitation,
S. Giuseppe Hospital IRCCS MultiMedica,
Milan University, Milan, Italy
e-mail: chiara.novelli@multimedica.it;
gpajardi@centrostudimano.it
Keywords
Congenital trigger · Trigger nger · Trigger
thumb · Splinting
Trigger thumb is one of the most common paediatric hand conditions and responds universally to
simple surgical release; however, trigger ngers
are more complex, often owing to systemic conditions or anatomical abnormalities, and require
consequently a wide and ample treatment.
Paediatric trigger thumb is a common condition. The reported specic incidence has
increased from one in 2000 new-borns two
decades ago to 3.3in 1000in a recent report [1].
It often presents in children at about 24months,
but can occur earlier, some times at about
6months, or later. Reports of siblings and twins
with trigger thumbs are common and some
patients report a positive family history, which
suggests a possible genetic predisposition [2, 3].
The aetiology of trigger thumb in children
remains uncertain. The main accredited hypothesis is that there is an anatomical mismatch
between the diameter of the tendon sheath and
the diameter of the exor pollicis longus (FPL)
tendon.
Khoshhal etal. [4] examined specimens from
the A1 pulley of children who had undergone
trigger thumb release and found both myobroblasts and cyto-contractile proteins (vimentin and
a-smooth muscle actin). The authors suggested
© Springer Nature Switzerland AG 2023
G. Pajardi (ed.), Pediatric Hand Surgery, https://doi.org/10.1007/978-3-031-30984-7_4
43
Соседние файлы в папке @xirurgi_2025