Published online July 10, 2006
PEDIATRICS Vol. 118 No. 2 August 2006, pp. e522-e525 (doi:10.1542/peds.2005-2737)
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EXPERIENCE AND REASON

Thoracolumbar Syrinx in Association With Williams Syndrome

David B. Cohen, MD and Matthew R. Quigley, MD

Department of Neurosurgery, Allegheny General Hospital, Pittsburgh, Pennsylvania


   ABSTRACT
TOP
 ABSTRACT
CASE REPORT
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
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.

Key Words: Williams syndrome • syrinx • genetics • scoliosis

Abbreviations: ELN, elastin • LIMK1, LIM kinase 1 • CSF, cerebrospinal fluid

Williams syndrome was described originally by Williams et al1 in 1961 and Beuren et al2,3 in 1962 and 1964. An autosomal dominant disorder resulting from a microdeletion on chromosome 7, its prevalence has been estimated to range from 1 in 7500 to 1 in 20000 live births.4,5 It is characterized by derangements in multiple body systems, including dysmorphic facies, supravalvular aortic stenosis and other arterial narrowing, mental retardation, a distinctive cognitive profile, and scoliosis, kyphosis, or lordosis of the spine.6–11 Although scoliosis is not uncommon in these patients, there have been no reports in the literature of syrinx in association with Williams syndrome.


   CASE REPORT
TOP
 ABSTRACT
 CASE REPORT
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
A 10-month-old girl was evaluated for thoracolumbar scoliosis. She had normal lower extremity tone and distal strength but some weakness in the proximal lower extremities. She did not crawl but, when placed in a sitting position, would rock back and forth. MRI of the thoracic and lumbar spine revealed a syrinx cavity extending from T10 to L2 (Figs 1 and 2). She was the product of a term, uncomplicated natural delivery with a birth weight of 2.77 kg (6 lb, 2 oz). The patient had been diagnosed with gastroesophageal reflux disease and had undergone corrective surgery for strabismus.


Figure 1
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  		FIGURE 1 Sagittal T2-weighted MRI of the thoracolumbar spine revealed a syrinx cavity extending from T10 to L2. No abnormal contrast enhancement was seen.

 

Figure 2
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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 enhancement was seen.

 
Because the syrinx appeared to be directly contributing to the scoliosis, a decision was made to treat the syrinx. When the girl was 13 months of age, we performed a T11 through L1 laminoplasty with drainage of the syrinx and placement of a syringosubarachnoid shunt. There were no complications from the procedure, and the patient was discharged from the hospital 3 days later with unchanged neurologic status. At follow-up 1 month after surgery, the patient had improved neurologically and would weight-bear in the lower extremities and cruise the room.

While the patient was in the hospital postoperatively, she was seen by a pediatric geneticist because of the suspicion of a genetic syndrome. At that time the diagnosis of Williams syndrome was made on the basis of her height (5th–10th percentile), her weight and head circumference (<5th percentile), and the typical facial appearance of Williams syndrome. The patient did not have a Chiari I malformation. Neither of the patient's parents had any typical features of Williams syndrome, and there was no family history of the disease. Karyotype and fluorescent in situ hybridization studies were performed, which revealed a 46,XX karyotype and a microdeletion in the Williams syndrome region of chromosome 7 (7q11.23), confirming the diagnosis.


   DISCUSSION
TOP
 ABSTRACT
 CASE REPORT
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Williams syndrome is a genetic disorder with manifestations in multiple body systems. Infants are typically born at term, with weight and length in or below the lower half of the normal range.11 The diagnosis is often delayed because of the lack of distinctive facial features at birth and absence of cardiac symptoms. Supravalvular aortic stenosis, peripheral pulmonary artery stenosis and other arterial narrowing, strabismus, and dysmorphic facial features (periorbital fullness, flat nasal bridge, poorly defined philtrum, thick lips, wide mouth, and small chin) are common components of the syndrome.6,8,11 Infants are hypotonic with hyperreflexia and lax joints,11 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 deficits 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 syndrome accounts for ~6% of all patients with mental retardation 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 20000 live births.4,5,10 The mutation almost always occurs sporadically, although there have been reports of inherited cases.14 Unequal recombination 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 maternal copy of chromosome 7 exhibit smaller stature than those with the deletion on their paternal chromosome 7.16 The microdeletion region contains 28 genes, of which 4 are highly expressed in the brain.15,17 Thus far, only 2 genes (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 supravalvular aortic stenosis, whereas LIMK1 is thought to affect the cognitive profile of patients with Williams syndrome, especially the ability to grasp spatial relationships.18 The role of LIMK1, however, is controversial, and recent evidence suggests that its deletion acts in concert with the deletion of other genes to produce the observed cognitive deficits.19 Specifically, this could occur via the effect of LIM kinase 1 on actin depolymerization and recycling, which has direct implications for axonal guidance during central nervous system development.4,10

Grossly, total brain volume in patients with Williams syndrome is slightly reduced, but some areas tend to be maintained while others are not.11 The frontal lobes and limbic system of the brain tend to be well preserved, which could relate to the maintenance of empathy and emotions. Preservation of the neocerebellum in association with preserved frontal lobes could also account for the fluent speech pattern.18 There is also evidence to suggest that the dorsal central sulcus is less likely to reach the interhemispheric fissure in patients with Williams syndrome than in control subjects, with no difference in the central sulcus observed ventrally, supporting the theory that many of the cognitive deficits are the result of dorsal forebrain maldevelopment.7

Although Williams syndrome has been associated with the multiple neurologic and structural abnormalities described above, including spinal deformities such as scoliosis, there has been no mention of spinal cord abnormalities. There is a known association between scoliosis and syringomyelia20; thus, in patients with Williams syndrome, scoliosis should not be assumed to be the result of the joint laxity and hypotonia that is recognized as part of the syndrome. In patients without Williams syndrome who have both scoliosis and a syrinx, the evidence suggests that treatment of the syrinx can result in stabilization or improvement of the scoliosis as well.21,22 Kontio et al23 noted in a retrospective review of 98 cases of children with scoliosis and syringomyelia that in almost half (48%), treatment of the syrinx resulted in no further progression of the scoliosis. In addition, scoliosis surgery in the setting of syringomyelia has been noted to be safe, without further neurologic deterioration.24 It has been noted, however, that spontaneous shrinkage of the syrinx and improvement in the scoliotic curve can occur in children undergoing nonoperative management.25

The pathogenesis of syrinx formation is still under debate. Gardner postulated that if cerebrospinal fluid (CSF) flow across the craniocervical junction is blocked, the arterial systolic pressure pulse in the choroid plexus is transmitted to the central canal of the spinal cord via the fourth ventricle and obex, resulting in dilation of the central canal.26 Williams hypothesized that negative pressure distal to a lesion, such as a tumor, located anywhere in the spinal canal causes fluid to be sucked into the cord, resulting in a syrinx. Usually, however, a communication is not observed between the fourth ventricle and syrinx, and there is not always a pressure differential proximal versus distal to a lesion. Ball and Dayan thus argued that fluid enters a syrinx cavity by dissecting along the Virchow-Robin spaces when upward flow is blocked by tonsillar descent.27 In support of this theory, there is evidence of macroscopic openings between spinal CSF and syrinx cavities, and contrast agents have been shown to enter a syrinx from the distal thecal sac without entering the ventricular system.26,27 None of these theories can adequately explain the presence of a syrinx in our case, in which no obstruction existed to CSF flow at the craniocervical junction or anywhere else in the spinal canal. Syrinxes have been noted in other congenital syndromes as well, including atypical hemifacial microsomia,28 Dandy-Walker malformation,29 mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome),30 Nager syndrome,31 and Carpenter syndrome.32 Syrinxes have also been reported in association with tethered-cord syndrome33 and Horner's syndrome.34,35 The association of syrinx and Williams syndrome in our index case suggests that regions of chromosome 7, overlapping the known site of Williams syndrome, could possibly be related to the occurrence of sporadic syrinx without concomitant Chiari malformation.


   CONCLUSIONS
TOP
 ABSTRACT
 CASE REPORT
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
To our knowledge, our report is the first of a patient with Williams syndrome and a spinal syrinx. The syrinx was felt to be contributing to the scoliosis and the observed motor deficits and was corrected surgically before repair of the scoliosis. The genetic defect causing Williams syndrome is not necessarily the direct cause of the syrinx, because this is the first known reported case of a syrinx occurring in conjunction with Williams syndrome. Many syrinxes may be missed, however, as a result of the lack of imaging of the spinal cord. Syrinxes are commonly associated with scoliosis, which is a recognized part of the syndrome. We therefore 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. In addition, regions of chromosome 7 may contain candidate genes in the search for the genetic basis of syringomyelia.


   FOOTNOTES
 
Accepted Feb 7, 2006.

Address correspondence to David B. Cohen, MD, Department of Neurosurgery, Allegheny General Hospital, 420 E North Ave, Suite 302, Pittsburgh, PA 15212. E-mail: dbcmd{at}hotmail.com

The authors have indicated they have no financial relationships relevant to this article to disclose.


   REFERENCES
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 ABSTRACT
 CASE REPORT
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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