Congenital scoliosis in monozygotic twins: case report and review of possible factors contributing to its development
Congenital scoliosis in monozygotic twins: case report and review of possible factors contributing to its development
Angelos Kaspiris 1
Theodoros B Grivas 1
Hans-Rudolf Weiss 0
0 Asklepios Katharina Schroth, Spinal Deformities Rehabilitation Centre , Korczakstrasse 2, D - 55566 Bad Sobernheim , Germany
1 Department of Trauma and Orthopaedics, "Thriasio" General Hospital - NHS , G. Gennimata Av. 19600, Magoula, Attica , Greece
Background: The exact etiology of congenital scoliosis remains unknown as yet. It seems that its development may be influenced by both genetic predisposition and environmental factors, at varying degrees. International bibliography features few cases of monozygotic twins with congenital scoliosis. The aim of this study is to report a case in monozygotic twins and review the literature relating to the description of similar cases as well as the pathophysiological mechanism involved in its development. Methods: Clinical examination and simple X-rays revealed scoliosis of differing degrees and types in male monozygotic twins with moderate mental retardation and dyslalia. Results: Congenital scoliosis identified in both twins. In the first, this was manifested as left thoracic scoliosis, with Cobb angle of 34 degrees while in the second as left thoracolumbar scoliosis with Cobb angle of 10 degrees. Both were found to suffer from incarcerated hemivertebrae. Conclusion: According to both its clinical identification and severity and to its course, not only the genetic but the environmental factors seem to play a leading role in the appearance of the condition.
Congenital scoliosis is the abnormal development of the
spine resulting in combination of missing portion, partial
formation, or lack of separation of the vertebras [
vertebral malformations spanned the length of the entire
spine and were classified as butterfly vertebrae,
segmentation defect, hypoplasia and hemivertebrae. Butterfly
vertebrae were defined by the presence of sagittal cleft [
Congenital scoliosis is often accompanied by other
dysplastic anomalies and may affect multiple organ systems.
It is characteristically described that its clinical
manifestation may be linked to around seventy different syndromes
]. Despite the large number of epidemiological and
clinical studies and extended research at molecular level,
its etiology remains unclear. This seems to implicate both
genetic and environmental factors. Our paper reports a
case of congenital scoliosis in monozygotic twins, to be
added to the very few cases found in international
The case involves two male monozygotic twins, born in
May 1992, following a full-term pregnancy. There was no
history of consanguinity of the parents. The mother's
history does not include exposure to smoke, toxins or drugs
during pregnancy and the family history does not feature
any cases of congenital spinal malformations. Congenital
scoliosis was diagnosed at the age of 11. Both twins are
1.71 m tall and weight 88 and 81 kg respectively.
Moderate thoracic curves were revealed in both upon clinical
examination (Figure 1). No pathological findings were
noted on the skin or subcutaneous tissue, while the
examination results for the remaining systems were within
normal limits. No accompanying musculoskeletal
abnormalities or neurological symptomatology were
noted, apart from moderate mental retardation and
dyslalia in both twins.
During the anterior-posterior spine X-ray examination we
identified at the first child a left scoliosis with a Cobb
angle of 34°. The upper curve is between Th6 and Th10
with semiincarcerated hemivertebrae while the lower
curve is between T10 and L2 (Figure 2). The second twin
has a left thoracolumbar scoliosis (Th9 – L1) with a Cobb
angle of 10° (Figure 3). The X-ray examination of the
pelvis showed this to be Risser grade 3, without further
development during the last semester of the examination. The
scoliosis has manifested a very limited gradual
progression since the time of diagnosis. Given the moderate
nature of the condition and its benign prognosis, neither
therapeutic treatment has been initiated nor further MRI
A written informed consent was obtained from the
patients for publication of this case report and
accompanying images. A copy of the written consent is available
for review by the Editor – in chief of this journal.
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Through the clinical evaluation of the twins in standing position the observation has revealed a slight shoulder
asymmetry that accompanied by a slight scapular and waist asymmetry in the first and a moderate asymmetry
of the above somatic areas in the second.
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Anterior posterior plain X-ray of the first twin at the age of 11 years demonstrates a left thoracic scoliosis with
an upper curve from Th6 – Th10 and a semiincarcarated hemivertebra and a lower curve Th10 – L2 with a
Cobb angle of 34°.
The frequency of congenital scoliosis is approximately
0.5, or 1 in 1,000 births. The etiological factors involved
in its development are unknown. Basic research has
implicated various environmental factors, such as the exposure
of the pregnant mother to carbon monoxide, the
consumption of alcohol [
] or the administration of
antiepileptic agents, such as valproic acid [
] and Dilantin
. Other factors that seem to participate in its
development are hyperthermia [
] or maternal Insulin
Dependent Diabetes Mellitus (IDDM) [
], but none of
the above have been confirmed to date by
epidemiological studies. However, few studies have taken place on the
influence of teratogenic substances, such as boric acid, on
lab animals [
] during pregnancy. Hence, their
effect on the formation of vertebral elements has not been
adequately studied; this would undoubtedly constitute a
very important future field of study that could lead to their
Various genetic factors have also been implicated in the
development of congenital scoliosis. Using chromosomal
deletion mapping, a large number of chromosomal
deletions, relating to regions 2p13 – 15, 6q13 and 15q12 have
been identified, leading to the conclusion that said
regions play a very important role in its development
There are very few reports of congenital scoliosis in
monozygotic twins. In specific, only twelve cases have
been described in international literature to date and in
only four of these did congenital scoliosis appear in both
oFCfihg1iul0dr°tew3o was first seen at the age of 11 and had a left thoraco lumbar scoliosis with a curve from Th9 – L1 and a Cobb angle
Child two was first seen at the age of 11 and had a left thoraco lumbar scoliosis with a curve from Th9 – L1 and
a Cobb angle of 10°.
]. In these cases, this genetic origin may not
be the only etiologic factor as these may include factors
influencing the intrauterine environment, such as
hypoxia, the administration of chemical substances or the
mother's diet, which lead to disturbances in segmental
blood flow to the vertebrae, causing congenital spinal
abnormalities. Junghans [
] and Tanaka [
] noted the
importance of the distribution of the inter-segmental
arteries for accurate vertebral body development.
Furthermore Tanaka et al [
] suggests that vascularization
process plays an important role in formation of the vertebral
body during the stage of resegmentation and early
chondrification. Any abnormal distribution of arteries may
induce a malformation. This specific hypothesis could
explain why, albeit genetically identical, monozygotic
twins develop scoliosis at different vertebral levels, as in
the currently reported case. This happens because the
above factors affect blood flow at different stages of fetal
development, thus affecting a different vertebral level.
In addition, theories on disturbances in somite formation
or failure in the creation of cartilage in the
mesenchymatous tissue try to explain the influence of environmental
factors during the intrauterine stage. Somitogenesis
describes the process of the formation of the spinal canal's
structural elements. In specific, between the 20th and 30th
day of embryogenesis, the mesenchymatous cells located
paraxially of the position of the future formation of the
spinal cord create spherical segmental structures, called
somites. Somites are transient embryonic structures that
are precursors of the most obvious examples of
segmentation in vertebrates: the vertebrae and the intervertebral
discs of the backbone, the rib cage and the dermis and
striated muscle of the back [
], and they form rhythmically
from the prosomitic mesoderm at a time period that is
characteristic of the species, ranging from 90 minutes in
chicken, 120 minutes in mouse to approximately 4 – 5
hours in humans [
]. The somites' migration and
division, which results in the creation of fetal sclerotomes
leads to the creation of vertebrae. The overall process
appears to be influenced by the cyclic expressed genes
participating in the Notch signaling pathway such as Lfng
(lunatic fringe), which is a glycosyl-transferase that
modifies the Notch receptor, Hes 1, Hes 5, Hes 7 and Hey1 in
mice. Various mutations affecting either core Notch
members (such as Notch1 gene or Notch coactivator RBKJk) or
several oscillator Notch pathway genes, lead to
disturbances in the formation of somites and abnormalities in
the vertebral elements of lab animals. Wnt/β-catenin
pathway via Axin 2 regulates negatively the above process.
Moreover, the Wnt 3a gene is necessary for generation of
the posterior portion of neuraxis, as knockout mice fail to
develop a tailbud and are truncated from a point slightly
anterior to the hind limbs. [
] Although Wnt3a has
been proposed to be a controlling gene in the oscillation
of Notch signaling, mutations in the above gene do not
appear to be a common reason for the development of
congenital vertebral malformations in humans [
The assumed influence of environmental factors is
reinforced by clinical cases of congenital scoliosis in only one
of two monozygotic twins. In particular, in monozygotic
twins with identical hair, skin and eye color, ear shape and
iridal patterns, and a large numbers of blood group
subtypes, only one would manifest congenital scoliosis that
would often be accompanied by abnormalities in other
systems, such as large ventricular septal defects. The other,
on the contrary, would be absolutely healthy [
The participation of developmental abnormalities from
other organs is extremely frequent. We should hence
investigate possible anomalies in the cardiovascular,
genitourinary and gastrointestinal systems. Cardiovascular
system anomalies coexist at a percentage of over 25%;
these may be quite mild or even severe, such as the
tetralogy of Fallot, Atrial or Ventricular Septal Defects or
Transposition of the great vessels. At high percentages of over
20% and up to 43%, congenital scoliosis may be
accompanied by genitourinary abnormalities. This could be due
to the fact that the genitourinary system and the spinal
canal originate in the fetal mesoderm and develop during
the fifth week of pregnancy. Ectopic, solitary or
lamelliform kidney, ureter duplication and hypospadia cases
have been reported. From the gastrointestinal system, the
accompanying clinical findings include
tracheooesophageal fistulas and esophageal atresia [
Nervous system anomalies may also be present at
percentages of up to 35%; these include diastematomyelia, Chiari
malformation and intradural lipomas. At this point, we
should note that the administration of folic acid may be
linked to the prevention of the above disorders [
Coexistent musculoskeletal abnormalities, such as
Developmental Dysplasia of the Hip, cavus feet and clubfeet or
rib cage deformities are not uncommon. Skin
participation has also been reported. Pathological pigmentation
tests, such as café-au-lait spots, hairy patches and skin tags
in the subcutaneous tissue of the scoliotic spinal cord
region are necessary. The simultaneous presence of
syndromes such as Sprengel Deformity, Klippel-Feil
syndrome, Goldenhar's syndrome (craniofacial disorders,
microtia, and epibulbar dermoids), Allagile syndrome,
Jarcho - Levin syndrome or VACTREL association
(Vertebral malformation, Cardiac malformations,
TracheoEsophageal fistula, Renal Radial anomalies and Limb
defects) require immediate identification and appropriate
therapeutic management in these patients.
This is why the diagnostic approach is of such importance.
Simple X-rays remain the most reliable indicator not only
for the diagnosis but also for the follow-up of these
]. At this point, we should note that
congenital scoliosis directly influences the respiratory function, as
it leads to an increasing asymmetry in lung size. According
to a study by Redding, Song et al, there is no correlation
between the Cobb angle and pulmonary functionality, so
the most reliable method of measuring pulmonary
asymmetry is not the measurement of the Cobb angle but a
ventilation lung scan .
In patients scheduled to undergo corrective operation, the
pre-operative use of CT-3D and cardiac U/S is deemed
important. In the event of suspected genitourinary
abnormalities, the most reliable diagnostic method involves U/
S tests. In cases of neurological symptomatology, spinal
cords MRIs have widely replaced myelograms in
identifying spinal dysraphism [
The present paper reports the case of two monozygotic
twins, which, albeit genetically identical, present scoliosis
at different vertebral levels and with differing deformation
grades. This fact, together with the review of the available
literature, is added to existing speculation on the extent of
influence of genetic and environmental factors during
intrauterine life in the development of congenital
Written patient consent was obtained for publication of
The authors declare that they have no competing interests.
TBG built the structure of the paper, performed part of the
literature review and revised the manuscript. HRW
examined, diagnosed and performed the clinical and X-ray
evaluation of the presenting cases as well as part of the
literature review and revised the manuscript. AK performed
part of the literature review and text editing. All authors
have read and approved the final manuscript.
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