Accepted Manuscript

Elongated conus medullaris, sacral agenesis and scoliosis- a case report of a patient
with trisomy 19q and monosomy 7q

Isabel Graul, Dr. med., Timo Zippelius, Dr. med., Alexander Hölzl, Dr. med., Patrick
Strube, PD

PII: S1878-8750(19)30048-8
DOI: https://doi.org/10.1016/j.wneu.2018.12.178
Reference: WNEU 11126

To appear in: World Neurosurgery

Received Date: 17 November 2018

Revised Date: 18 December 2018
Accepted Date: 20 December 2018

Please cite this article as: Graul I, Zippelius T, Hölzl A, Strube P, Elongated conus medullaris,
sacral agenesis and scoliosis- a case report of a patient with trisomy 19q and monosomy 7q, World
Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2018.12.178.

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 ACCEPTED MANUSCRIPT
Elongated conus medullaris, sacral agenesis and scoliosis- a case report of a patient with trisomy 19q and
monosomy 7q

Running head

Elongated conus medullaris, sacral agenesis and scoliosis

Isabel Graul, Dr. med.1, Timo Zippelius, Dr. med.1, Alexander Hölzl, Dr. med.1, Patrick Strube, PD1

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1 Orthopedic department, University Hospital Jena, Campus Eisenberg, Germany

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Corresponding author:

Dr. med. Isabel Graul

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Orthopedic department

University Hospital Jena, Campus Eisenberg

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Germany
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Klosterlausnitzer Str. 81

07607 Eisenberg
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036691-81272

isabel.graul@med.uni-jena.de
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ORCID ID: 0000-0002-8508-1174

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Author contributions

All authors contributed toward data analysis, drafting and revising the paper and agree to be responsible for all
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aspects of the work.

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Key words:
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Sacral agenesis, conus medullaris elongation, monosomy 7q, trisomy 19q

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1 Abstract:

2 Background: Both progression of scoliosis following completion of growth, and the combination of low mental
3 retardationand the conspicuous sagittal clinical and radiographic abnormalities suggest a secondary genesis of
4 the scoliosis according to a genetic aberration.

5 Case Discription: In the outpatient department, an 18-year-old girl presents with scoliosis and mild mental
6 retardation. Radiography findings demonstrate a sacral agenesis and the consecutively performed MRI a conus

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7 depression.

8 Due to the symptom constellation, a genetic syndrome was suspected. Genetic diagnostics revealed a trisomy

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9 19q and monosomy 7q. Usually, deletions of the subtelomer 7q show a phenotype with growth retardation, facial
10 anomalies and intellectual deficit, trisomy of the subtelomer 19q growth retardation, atypical ears, short neck and
11 intellectual deficit with delayed development.

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12 The further clinical radiological and neurological examination showed no evidence of a tethered cord syndrome.
13 The correction of scoliosis was carried out under intraoperative neurophysiological monitoring without

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14 neurologic complications.
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15 Conclusions: In the presence of dysplastic sacral changes and accompanying elongated conus medullaris in
16 patients with scoliosis, it is always necessary to think of rare chromosome aberrations and to initiate appropriate
17 diagnostics before surgery. The intraoperative neurophysiological monitoring is strongly recommended, due to a
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18 morphologically not fully-excludable tethered cord syndrome.

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24 Key words:
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25 Sacral agenesis, conus medullaris elongation, monosomy 7q, trisomy 19

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26 Anamnesis:
27 In December 2016 an 18-year-old girl was presented with scoliosis for surgical treatment in our outpatient clinic
28 Despite completed growth and previous brace treatment, a progressive decline of posture was reported, as

29 manifested through increasing lateral tilt of the spine to the right and initial restriction of respiratory function
30 during sports activities. Additionally she reported on recurrent back pain, in particular at night.
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32 The patient has two siblings without hereditary diseases. Genetic diagnostics revealed no chromosome

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33 translocation in the genome of the mother. A detailed examination of her father was not available. Because of the
34 slight mental retardation of so far unknown reason, she had to attend a special school. At this time school sports
35 were possible with slight respiratory limitations. Beside this, all other everyday activities could be carried out

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36 without difficulty.

37 Clinical findings:

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38 On examination, patient’s height (1.52m) and weight (49kg) were appropriate for age.
39 She was born by normal vaginal delivery, following an uneventful pregnancy of a non-diabetic mother. Her birth

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40 weight was low (2120g) with a normal body length of 48cm. She showed no difficulties in sitting, standing or
41 walking. Due to the scoliotic deformity, the torso was tilted to the right with a significant lateral shift of the
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42 occiput to the right of about 5 cm. There was a more pronounced shoulder on the right side and a rib hump on
43 the right side. In stance, we found a reduced kyphosis of the thoracic spine and increased lordosis of the lumbar
44 spine. The pelvis had an anterior tilt when standing in an upright position with a pelvic obliquity right +1.5 cm
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45 and shortened hip flexor muscles. She presented with smooth walking without the need of a walker or crutches.
46 The muscle silhouette of the lower extremities was formed equally between left and right. The muscle tonus was
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47 normal without spasticity. There were no asymmetries in the lower extremities. (figure 1)
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49 A mild mental retardation could be observed. In further diagnostics, no additional malformations or diseases
50 could be detected. The organ functions appeared normal.
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52 Radiographical findings

53 In preoperative X-ray diagnostics, a partial sacral agenesis (sacral hypoplasia) as well as a shortened lumbar
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54 spine of 4 vertebras was detected. The pelvis showed a pelvic tilt of 28 ° (norm 13.6 ° +/- 6 °), a sacral slope of
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55 74 ° (norm 43.2 ° +/- 8.4) and a pelvic incidence of 91 ° (norm 56 ° +/- 10). The sagittal vertebral axis (SVA)
56 was 67 mm.
57 The thoracic kyphosis was 10 ° (Th4 to Th12 norm 41 ° +/- 10) and the lumbar lordosis was rather large with 70
58 ° (L1 to L4 with 4 free lumbar vertebras norm values 44 ° +/- 11 °).1
59 The deformity’s Cobb angle p.a. from Th4 to L1 was 45 °.
60 (figure 2)
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62 Magnetic Resonance Imaging findings
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64 MRI revealed a rudimentary disc S1 / S2. The sacrum ended at the level S2. The agenesis of the sacrum was
65 symmetrical and classified as type II according to Renshaw 2. (table 1) The deep-seated conus medullaris was
66 noticeable, the spinal cord forming fibers continued to run bundled to S1 / 2. (figure 3)
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68 Findings of genetic analysis
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70 Due to the conspicuous spinal morphology, a genetic examination was preoperatively initiated. This was
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performed by means of molecular genetic analysis of the subtelomere (fluorescence in-situ hybridization and
72 multiplex ligation-dependent sample amplification method). The results indicated a deletion of the subtelomere
73 region in the q-arm of a chromosome 7 and a duplication of the subtelomeric region in the q-arm of a

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74 chromosome 19 resulted in partial monosomy 7q and partial trisomy 19q.
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Findings of neurologic examination and functional diagnostics
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78 The neurologic examination did not disclose any abnormal findings. Neither neurologic deficits, deep sensory

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79 disturbances, temperature sensory disturbances, pathological reflexes, nor other syndromes of the corticospinal
80 tracts could be found. In addition, there were no bladder or rectal disorders. An uroflow dynamic measurement
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81 did not reveal any pathological findings.
82 The electrophysiological examination using SSEP also showed no abnormalities.
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84 Treatment and follow-up

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86 The scoliosis of the spine was treated with a posterior release and correction from Th3 to L3. Intraoperatively,
87 physiological SSEPs and MEPs were evident at all times. The deformity (Cobb angle p.a. Th4 to L1) could be
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88 reduced to 12 °. Sacral agenesis was not treated surgically. The postoperative lumbar lordosis (L1-4) was
89 lowered to 45 °, the thoracic kyphosis (Th4-12) remained constant. The postoperative sacral slope was 51 °, the
90 pelvic tilt increased to 39 °. Despite the SVA remaining stable at 67 mm, the C7 plumb line was shifted back to
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91 the femoral head center. This was accompanied by a decrease of kyphosis of the cervical spine from 13 to 7 °
92 (C2-6) (figure 4, 5).
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94 Postoperativly, the patient developed a wound dehiscence. The revision surgery was performed at the 17th day
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95 postoperatively. The intraoperative microbiological samples remained sterile. A prophylactic systemic antibiotic
96 medication with a 2nd generation cephalosporin was given for 2 weeks. Thereafter, the wound healing showed
97 no abnormalities. The mobilization took place immediately after the operation without any restrictions.
98 3 months postoperatively, the girl presented again, the clinical functional tests showed a mobilisation-
99 unrestricted teenager. The wound did not reveal any pathological findings. Pain medication was no longer
100 necessary and the patient participated in school education.
101 The sagittal profile was not altered presenting the compensated flattened kyphosis and increased lordosis as well

102 as the pronounced anterior pelvic tilt. Nevertheless, gait and standing tests could be performed without difficulty

103 and the patient presented without neurologic deficits.

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104
105 Discussion
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107 This case illustrates the need for throughout diagnostic workup in scoliosis patients. Both, the progression of
108 scoliosis following completion of growth, and the combination of slight mental retardation, as well as the
109 conspicuous sagittal clinical and radiographic abnormalities suggest a secondary genesis of the scoliosis
110 according to a genetic aberration. In this case, extended radiological diagnostics including MRI imaging as well
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as a genetic examination should be initiated. Especially in the presence of partial sacral agenesis, further
112 malformations should always be expected, which could possibly complicate a scoliosis correction surgery.
113 Thus, changes in the spinal cord have been frequently observed in such dysplasia. In the study of 10 patients

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114 with prenatally diagnosed sacral agenesis Mottet et al. found six lipomas, four tethered cords, two
115 diastematomyelies, one syringomyely, and four low-lying truncated conus medullaris 3.

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116 Especially with the additional existence of a conus depression, a tethered cord syndrome is to be expected 4.
117 Nevertheless, because of a short lumbar segment and the sacrum agenesis the interpretation of the conus level
118 can be rather difficult. Therefore, additional pre- and intraoperative neurophysiological investigations are highly

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119 recommended 5.
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120 Sacral agenesis (part of the caudal regression syndrome) is a rare and represents a severe sacral developmental
121 abnormality. Incidence is 1 per 25,000 live births. So far, a diagnostic algorithm is not available.
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122 Sacral agenesis is described to result from mutation of different genes. The sacral agenesis in chromosome
123 aberrations mentioned in the literature are most often associated with a deletion of the terminal 7q subtelomer
region 6. Lynch et al. also showed a correlation of the genes for holoprosencephaly and sacral agenesis with the
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125 differentiation of the mesodermal cell line at both ends of the developing notochords 7.
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126 The underlying numerical chromosome aberration of the presented case with translocation is very rare. The
127 mosaic image of deletion of the subtelomeric region in the q-arm of chromosome 7 is superimposed by the
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128 duplication of the subtelomeric region in the q-arm of chromosome 19.

129 The cases of trisomy on subtelomere 19q described in the literature are characterized by low birth weight, small
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body size, atypical ears, short neck, intellectual retardation, delayed motor development, and delayed speech
131 development 8-10. Monosomy at subtelomer 7q again shows a phenotype with growth retardation, facial shape
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132 abnormalities, and mental retardation 11,12. In three documented cases, anal stenosis and sacral hypoplasia with
133 tumor formation have been described 13,14.
134 The patient showed a mild expression of the abovementioned multiple malformation patterns, which makes it
135 much more difficult to recognize the genetic abberation. In addition, the 18-year-old girl was not clinically
136 impaired by the conus depression or by the sacral agenesis until the growth was completed. She also had no
137 symptoms of tethered cord syndrome, which often becomes clinically symptomatic during growth.
138 Retrospectively, a pathological tethering was likely not present, as the correction surgery did not imply any
139 problems. Nevertheless, because preoperative neurophysiological diagnostics do not fully exclude a
140 perioperative complication, we suggest that the intraoperative neuromonitoring should be obligatory 15-18.
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142 In patients with scoliosis, if a conspicuous sagittal profile or progression of deformity after growth is completed
143 is seen and if additive symptoms of mental retardation as well as radiological abnormalities such as sacral
144 agenesis are present, supplementary genetic examination should be performed. In addition, an MRI is obligatory
145 for the exclusion of further spinal and neural malformations. Preoperative and intraoperative neurophysiological
146 diagnostics seem to be urgently recommended, especially if conus depression is suspected.

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149 Acknowledgments

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150 None.

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152 Disclosure

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153 This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-
154 profit sectors.
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170 Figure Legend

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172 Figure 1 Preoperative clinical image in standing position showing the pathologic shape and posture in
173 (a-left) posterior view and (b-right) lateral view.

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175 Figure 2 Preoperative whole spine radiographs in standing position showing the secondary scoliosis and
176 the pathologic sagittal profile with thoracic hypokyphosis and lumbar hyperlordosis. (a-left)
177 p.a. view, (b- right) lateral view.

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179 Figure 3 Preoperative MRI (sagital T2 weighted imaging), showing the medullary cone ending at the
180 level S1/2.

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182 Figure 4 Postoperative clinical image in standing position with partial normalization of the body shape
183 and posture. (a-left) posterior view, (b-right) lateral view.

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185 Figure 5 Postoperative whole spine radiographs in standing position showing the 3D-correction by the
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186 posterior instrumentation Th3 – L3. (a-left) p.a. view, (b-right) lateral view.
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Abbreviations

MEP motor evoked potential

MRI Magnetic Resonance Imaging
p.a. posteroanterior
SVA sagittal vertebral axis

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SSEP somatosensory evoked potential

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