Thoracolumbar Syrinx in Association With Williams Syndrome

Thoracolumbar Syrinx in Association With Williams Syndrome
David B. Cohen and Matthew R. Quigley
Pediatrics 2006;118;e522-e525; originally published online Jul 10, 2006;
DOI: 10.1542/peds.2005-2737
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EXPERIENCE & REASON
Thoracolumbar Syrinx in Association With Williams
Syndrome
David B. Cohen, MD, Matthew R. Quigley, MD
Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, Pennsylvania
The authors have indicated they have no financial relationships relevant to this article to disclose.
ABSTRACT
Williams syndrome is a genetic condition caused by a deletion on chromosome 7. Clinically it consists of multiple
cardiovascular and craniofacial structural abnormalities as well as developmental delay, specific cognitive difficulties,
and a characteristic personality. Although scoliosis is a noted manifestation of the disorder, syrinx in association with
Williams syndrome has not been reported previously in the literature. Here we present the case of a child with
Williams syndrome, scoliosis, and a thoracolumbar syrinx that was successfully treated surgically. We recommend
that children with Williams syndrome and scoliosis undergo preoperative evaluation of the spinal cord, as well as the
spinal column, so that correctable lesions such as a syrinx are not overlooked. Although syrinxes are often associated
with scoliosis, the association in this case of syrinx and Williams syndrome could imply the existence of a genetic
contribution to syrinx formation on chromosome 7.
WILLIAMS SYNDROME WAS described originally by Whenthegirlwas13monthsofage,weperformedaT11
Williams et al1 in 1961 and Beuren et al2,3 in
through L1 laminoplasty with drainage of the syrinx and
1962 and 1964. An autosomal dominant disorder result-
placement of a syringosubarachnoid shunt. There were no
ing from a microdeletion on chromosome 7, its preva-
complications from the procedure, and the patient was
lence has been estimated to range from 1 in 7500 to 1 in
discharged from the hospital 3 days later with unchanged
20 000 live births.4,5 It is characterized by derangements
neurologic status. At follow-up 1 month after surgery, the
in multiple body systems, including dysmorphic facies,
patient had improved neurologically and would weight-
supravalvular aortic stenosis and other arterial narrow-
bear in the lower extremities and cruise the room.
ing, mental retardation, a distinctive cognitive profile,
While the patient was in the hospital postoperatively,
and scoliosis, kyphosis, or lordosis of the spine.6–11 Al-
she was seen by a pediatric geneticist because of the
though scoliosis is not uncommon in these patients,
suspicion of a genetic syndrome. At that time the diag-
there have been no reports in the literature of syrinx in
nosis of Williams syndrome was made on the basis of her
association with Williams syndrome.
height (5th–10th percentile), her weight and head cir-
cumference ( 5th percentile), and the typical facial ap-
CASE REPORT
pearance of Williams syndrome. The patient did not
A 101⁄2-month-old girl was evaluated for thoracolumbar
have a Chiari I malformation. Neither of the patient’s
scoliosis. She had normal lower extremity tone and dis-
tal strength but some weakness in the proximal lower
parents had any typical features of Williams syndrome,
extremities. She did not crawl but, when placed in a
and there was no family history of the disease. Karyo-
sitting position, would rock back and forth. MRI of the
type and fluorescent in situ hybridization studies were
thoracic and lumbar spine revealed a syrinx cavity ex-
Key Words: Williams syndrome, syrinx, genetics, scoliosis
tending from T10 to L2 (Figs 1 and 2). She was the
Abbreviations: ELN, elastin; LIMK1, LIM kinase 1; CSF, cerebrospinal fluid
product of a term, uncomplicated natural delivery with a
www.pediatrics.org/cgi/doi/10.1542/peds.2005-2737
birth weight of 2.77 kg (6 lb, 2 oz). The patient had been
doi:10.1542/peds.2005-2737
diagnosed with gastroesophageal reflux disease and had
Accepted for publication Feb 7, 2006
undergone corrective surgery for strabismus.
Address correspondence to David B. Cohen, MD, Department of Neurosurgery, Allegheny General
Because the syrinx appeared to be directly contribut-
Hospital, 420 E North Ave, Suite 302, Pittsburgh, PA 15212. E-mail: dbcmd@hotmail.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2006 by the
ing to the scoliosis, a decision was made to treat the syrinx.
American Academy of Pediatrics
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and gastroesophageal reflux is seen as well. Short stature
is frequent, especially during infancy and childhood.8
Neurologically, there is a well-defined spectrum of def-
icits including mild mental retardation (IQ between 55
and 60), delayed expressive and receptive language
skills, multiple developmental motor disabilities, a high
incidence of anxiety and phobias, and an inappropriately
friendly personality.8,10 Cognitively, affected individuals
demonstrate relatively intact language skills with severe
visuospatial deficits, a preserved ability to process faces,
lack of fear of strangers, highly affective speech, and an
increased interest in, and ability for, music.7 Williams syn-
drome accounts for
6% of all patients with mental retar-
dation of genetic etiology.5 Exaggerated kyphosis/lordosis
or scoliosis of the spine is common.6,8,12 There have also
been reports of a possible increased incidence of Chiari type
I malformations in association with Williams syndrome,
which are caused by a decrease in volume of the bony
posterior fossa with a normal-sized cerebellum. There have
been too few reported cases, however, to draw a firm
conclusion about the existence of an association between
Chiari I malformation and Williams syndrome.13
Resulting from a microdeletion on chromosome 7 at
position q11.23, Williams syndrome has been estimated
to occur in
1 in 7500 to 1 in 20 000 live births.4,5,10 The
mutation almost always occurs sporadically, although
there have been reports of inherited cases.14 Unequal re-
combination during meiosis is thought to be the most
common mechanism for producing the mutation,4,10,15 and
the deletion seems to be as likely to be maternally derived
as paternally derived. However, there is evidence to suggest
that those individuals who have the deletion on their ma-
ternal copy of chromosome 7 exhibit smaller stature than
those with the deletion on their paternal chromosome 7.16
FIGURE 1
The microdeletion region contains 28 genes, of which 4 are
Sagittal T2-weighted MRI of the thoracolumbar spine revealed a syrinx cavity extending
highly expressed in the brain.15,17 Thus far, only 2 genes
from T10 to L2. No abnormal contrast enhancement was seen.
(elastin [ELN] and LIM kinase 1 [LIMK1]) have been
shown to contribute to the symptoms of the disorder.10
ELN has been implicated in the pathogenesis of supraval-
performed, which revealed a 46,XX karyotype and a
vular aortic stenosis, whereas LIMK1 is thought to affect the
microdeletion in the Williams syndrome region of chro-
cognitive profile of patients with Williams syndrome, es-
mosome 7 (7q11.23), confirming the diagnosis.
pecially the ability to grasp spatial relationships.18 The role
of LIMK1, however, is controversial, and recent evidence
DISCUSSION
suggests that its deletion acts in concert with the deletion of
Williams syndrome is a genetic disorder with manifesta-
other genes to produce the observed cognitive deficits.19
tions in multiple body systems. Infants are typically born
Specifically, this could occur via the effect of LIM kinase 1
at term, with weight and length in or below the lower
on actin depolymerization and recycling, which has direct
half of the normal range.11 The diagnosis is often delayed
implications for axonal guidance during central nervous
because of the lack of distinctive facial features at birth
system development.4,10
and absence of cardiac symptoms. Supravalvular aortic
Grossly, total brain volume in patients with Williams
stenosis, peripheral pulmonary artery stenosis and other
syndrome is slightly reduced, but some areas tend to be
arterial narrowing, strabismus, and dysmorphic facial
maintained while others are not.11 The frontal lobes and
features (periorbital fullness, flat nasal bridge, poorly
limbic system of the brain tend to be well preserved,
defined philtrum, thick lips, wide mouth, and small
which could relate to the maintenance of empathy and
chin) are common components of the syndrome.6,8,11
emotions. Preservation of the neocerebellum in associa-
Infants are hypotonic with hyperreflexia and lax joints,11
tion with preserved frontal lobes could also account for
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FIGURE 2
Sagittal T2-weighted MRI of the thoracolumbar spine revealed a
syrinx cavity extending from T10 to L2. No abnormal contrast en-
hancement was seen.
the fluent speech pattern.18 There is also evidence to
The pathogenesis of syrinx formation is still under
suggest that the dorsal central sulcus is less likely to
debate. Gardner postulated that if cerebrospinal fluid
reach the interhemispheric fissure in patients with Wil-
(CSF) flow across the craniocervical junction is blocked,
liams syndrome than in control subjects, with no differ-
the arterial systolic pressure pulse in the choroid plexus
ence in the central sulcus observed ventrally, supporting
is transmitted to the central canal of the spinal cord via
the theory that many of the cognitive deficits are the
the fourth ventricle and obex, resulting in dilation of the
result of dorsal forebrain maldevelopment.7
central canal.26 Williams hypothesized that negative
Although Williams syndrome has been associated
pressure distal to a lesion, such as a tumor, located
with the multiple neurologic and structural abnormali-
anywhere in the spinal canal causes fluid to be sucked
ties described above, including spinal deformities such as
into the cord, resulting in a syrinx. Usually, however, a
scoliosis, there has been no mention of spinal cord ab-
communication is not observed between the fourth ven-
normalities. There is a known association between sco-
tricle and syrinx, and there is not always a pressure
liosis and syringomyelia20; thus, in patients with Wil-
differential proximal versus distal to a lesion. Ball and
liams syndrome, scoliosis should not be assumed to be
Dayan thus argued that fluid enters a syrinx cavity by
the result of the joint laxity and hypotonia that is rec-
dissecting along the Virchow-Robin spaces when up-
ognized as part of the syndrome. In patients without
ward flow is blocked by tonsillar descent.27 In support of
Williams syndrome who have both scoliosis and a syr-
this theory, there is evidence of macroscopic openings
inx, the evidence suggests that treatment of the syrinx
between spinal CSF and syrinx cavities, and contrast
can result in stabilization or improvement of the scoliosis
agents have been shown to enter a syrinx from the distal
as well.21,22 Kontio et al23 noted in a retrospective review
thecal sac without entering the ventricular system.26,27
of 98 cases of children with scoliosis and syringomyelia
None of these theories can adequately explain the pres-
that in almost half (48%), treatment of the syrinx re-
ence of a syrinx in our case, in which no obstruction
sulted in no further progression of the scoliosis. In addi-
existed to CSF flow at the craniocervical junction or
tion, scoliosis surgery in the setting of syringomyelia has
anywhere else in the spinal canal. Syrinxes have been
been noted to be safe, without further neurologic dete-
noted in other congenital syndromes as well, including
rioration.24 It has been noted, however, that spontane-
atypical hemifacial microsomia,28 Dandy-Walker malfor-
ous shrinkage of the syrinx and improvement in the
mation,29 mucopolysaccharidosis type VI (Maroteaux-
scoliotic curve can occur in children undergoing nonop-
Lamy syndrome),30 Nager syndrome,31 and Carpenter
erative management.25
syndrome.32 Syrinxes have also been reported in associ-
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ation with tethered-cord syndrome33 and Horner’s syn-
12. Osebold WR, King HA. Kyphoscoliosis in Williams syndrome.
drome.34,35 The association of syrinx and Williams syn-
Spine. 1994;19:367–371
13. Pober BR, Filiano JJ. Association of Chiari I malformation and
drome in our index case suggests that regions of
Williams syndrome. Pediatr Neurol. 1995;12:84 – 88
chromosome 7, overlapping the known site of Williams
14. Metcalfe K. Williams syndrome: an update on clinical and
syndrome, could possibly be related to the occurrence of
molecular aspects. Arch Dis Child. 1999;81:198 –200
sporadic syrinx without concomitant Chiari malformation.
15. Schultz RT, Grelotti DJ, Pober B. Genetics of childhood
disorders: XXVI. Williams syndrome and brain-behavior rela-
tionships. J Am Acad Child Adolesc Psychiatry. 2001;40:606 – 609
CONCLUSIONS
16. Ashkenas J. Williams syndrome starts making sense. Am J Hum
To our knowledge, our report is the first of a patient with
Genet. 1996;59:756 –761
17. Bhattacharjee Y. Friendly faces and unusual minds. Science.
Williams syndrome and a spinal syrinx. The syrinx was
2005;310:802– 804
felt to be contributing to the scoliosis and the observed
18. Lenhoff HM, Wang PP, Greenberg F, Bellugi U. Williams syn-
motor deficits and was corrected surgically before repair
drome and the brain. Sci Am. 1997;277:68 –73
of the scoliosis. The genetic defect causing Williams syn-
19. Gray V, Karmiloff-Smith A, Funnell E, Tassabehji M. In-depth
drome is not necessarily the direct cause of the syrinx,
analysis of spatial cognition in Williams syndrome: a critical
assessment of the role of the LIMK1 gene. Neuropsychologia.
because this is the first known reported case of a syrinx
2006;44:679 – 685
occurring in conjunction with Williams syndrome.
20. Kuntz C IV, Shaffrey CI, Wolcott WP. Approach to the patient
Many syrinxes may be missed, however, as a result of
and medical management of spinal disorders. In: Winn HR, ed.
the lack of imaging of the spinal cord. Syrinxes are
Youmans Neurological Surgery. 5th ed. Philadelphia, PA: Elsevier;
commonly associated with scoliosis, which is a recog-
2004:4289 – 4326
21. Hanieh A, Sutherland A, Foster B, Cundy P. Syringomyelia in
nized part of the syndrome. We therefore recommend
children with primary scoliosis. Childs Nerv Syst. 2000;16:200 –202
that children with Williams syndrome and scoliosis un-
22. Mollano AV, Weinstein SL, Menezes AH. Significant scoliosis
dergo preoperative evaluation of the spinal cord as well
regression following syringomyelia decompression: case re-
as the spinal column so that correctable lesions such as a
port. Iowa Orthop J. 2005;25:57–59
syrinx are not overlooked. In addition, regions of chro-
23. Kontio K, Davidson D, Letts M. Management of scoliosis and
syringomyelia in children. J Pediatr Orthop. 2002;22:771–779
mosome 7 may contain candidate genes in the search for
24. Charry O, Koop S, Winter R, et al. Syringomyelia and scoliosis:
the genetic basis of syringomyelia.
a review of twenty-five pediatric patients. J Pediatr Orthop.
1994;14:309 –317
25. Tokunaga M, Minami S, Isobe K, Moriya H, Kitahara H, Nakata
REFERENCES
Y. Natural history of scoliosis in children with syringomyelia.
1. Williams JCP, Barratt-Boyes BG, Lowe JB. Supravalvular aortic
J Bone Joint Surg Br. 2001;83:371–376
stenosis. Circulation. 1961;24:1311–1318
26. Gower DJ, Pollay M, Leech R. Pediatric syringomyelia. J Child
2. Beuren AJ, Apitz J, Harmjanz D. Supravalvular aortic stenosis
Neurol. 1994;9:14 –21
in association with mental retardation and a certain facial
27. Batzdorf U. Syringomyelia, Chiari malformation, and hydro-
appearance. Circulation. 1962;26:1235–1240
myelia. In: Youmans JR, ed. Neurological Surgery: A Comprehen-
3. Beuren AJ, Schulze C, Eberle P, Harmjanz D, Apitz J. The
sive Reference Guide to the Diagnosis and Management of Neurosur-
syndrome of supravalvular aortic stenosis, peripheral pulmo-
gical Problems. Vol 2. 4th ed. Philadelphia, PA: WB Saunders;
nary stenosis, mental retardation and similar facial appearance.
1996:1090 –1093
Am J Cardiol. 1964;13:471– 482
28. Sze RW, Gruss JS, Cunningham ML. Unilateral aplasia of the
4. Donnai D, Karmiloff-Smith A. Williams syndrome: from geno-
middle cranial fossa floor in atypical hemifacial microsomia.
type through to the cognitive phenotype. Am J Med Genet.
AJNR Am J Neuroradiol. 2001;22:1434 –1437
2000;97:164 –171
29. Hammond CJ, Chitnavis B, Penny CC, Strong AJ. Dandy-
5. Stromme P, Bjornstad PG, Ramstad K. Prevalence estimation of
Walker complex and syringomyelia in an adult: case report and
Williams syndrome. J Child Neurol. 2002;17:269 –271
discussion. Neurosurgery. 2002;50:191–194
6. American Academy of Pediatrics, Committee on Genetics.
30. Hite SH, Krivit W, Haines SJ, Whitley CB. Syringomyelia in
Health care supervision for children with Williams syndrome.
mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome):
Pediatrics. 2001;107:1192–1204
imaging findings following bone marrow transplantation. Pe-
7. Galaburda AM, Schmitt JE, Atlas SW, Eliez S, Bellugi U, Reiss
diatr Radiol. 1997;27:736 –738
AL. Dorsal forebrain anomaly in Williams syndrome. Arch Neu-
31. Groeper K, Johnson JO, Braddock SR, Tobias JD. Anaesthetic
rol. 2001;58:1865–1869
implications of Nager syndrome. Paediatr Anaesth. 2002;12:
8. Lashkari A, Smith AK, Graham JM. Williams-Beuren
365–368
syndrome: an update and review for the primary physician.
32. Islek I, Kucukoduk S, Incesu L, Selcuk MB, Aygun D. Carpen-
Clin Pediatr (Phila). 1999;38:189 –208
ter syndrome: report of two siblings. Clin Dysmorphol. 1998;7:
9. Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL.
185–189
Natural history of Williams syndrome: physical characteristics.
33. Ng WH, Seow WT. Tethered cord syndrome preceding syrinx
J Pediatr. 1988;113:318 –326
formation: serial radiological documentation. Childs Nerv Syst.
10. Osborne L, Pober B. Genetics of childhood disorders: XXVII.
2001;17:494 – 496
Genes and cognition in Williams syndrome. J Am Acad Child
34. Kerrison JB, Biousse V, Newman NJ. Isolated Horner’s syn-
Adolesc Psychiatry. 2001;40:732–735
drome and syringomyelia. J Neurol Neurosurg Psychiatry. 2000;
11. Kaplan P, Wang PP, Francke U. Williams (Williams Beuren)
69:131–132
syndrome: a distinct neurobehavioral disorder. J Child Neurol.
35. Pomeranz H. Isolated Horner syndrome and syrinx of the
2001;16:177–190
cervical spinal cord. Am J Ophthalmol. 2002;133:702–704
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Thoracolumbar Syrinx in Association With Williams Syndrome
David B. Cohen and Matthew R. Quigley
Pediatrics 2006;118;e522-e525; originally published online Jul 10, 2006;
DOI: 10.1542/peds.2005-2737
Updated Information
including high-resolution figures, can be found at:
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