|Year : 2014 | Volume
| Issue : 3 | Page : 137-138
A complex craniovertebral junction malformation in a patient with late onset glycogenosis 2
Mariasofia Cotelli1, Marco Fontanella2, Alessandro Padovani1, Massimiliano Filosto1
1 Unit of Clinical Neurology, Section for Neuromuscular Diseases and Neuropathies, University Hospital "Spedali Civili" - Brescia, Italy
2 Unit of Neurosurgery, University Hospital "Spedali Civili" - Brescia, Italy
|Date of Web Publication||7-Oct-2014|
Clinical Neurology, University Hospital "Spedali Civili", Pz.le Spedali Civili 1, 25100 Brescia
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Glycogenosis II (GSDII) is an autosomal recessive lysosomal storage disorder resulting from deficiency of acid alpha-glucosidase and subsequent lysosomal accumulation of glycogen in skeletal, cardiac and smooth muscles. The late-onset form is characterized by wide variability of the phenotypical spectrum. Clinical findings may include muscle weakness, respiratory insufficiency, vascular abnormalities, low bone mineral density and higher risk of developing osteoporosis. Craniovertebral junction (CVJ) malformations have never been described so far. We here report on a GSDII 43-year-old woman who harbored the mutations IVS1-13T>G and c.2237G>A in the acid alpha-glucosidase gene. She recurrently suffered from headache, neck pain and dizziness. Brain MRI and CT scan showed the presence of a very rare complex CVJ malformation composed of basilar invagination, basiocciput hypoplasia, partial C1 assimilation, C1 posterior arch aplasia and C1 lateral mass hypoplasia and offset. Although we cannot rule out their coincidental occurrence, the rarity of multiple CVJ malformations in the general population as well as the well-known GSDII multisystem involvement should suggest to study the CVJ in the diagnostic process of GSDII patients in order to assess the CVJ malformation frequency in GSDII population and verify a possible relationship between these two conditions.
Keywords: Craniovertebral junction malformation, CVJ, GSDII, late - onset glycogenosis
|How to cite this article:|
Cotelli M, Fontanella M, Padovani A, Filosto M. A complex craniovertebral junction malformation in a patient with late onset glycogenosis 2. J Craniovert Jun Spine 2014;5:137-8
|How to cite this URL:|
Cotelli M, Fontanella M, Padovani A, Filosto M. A complex craniovertebral junction malformation in a patient with late onset glycogenosis 2. J Craniovert Jun Spine [serial online] 2014 [cited 2022 May 29];5:137-8. Available from: https://www.jcvjs.com/text.asp?2014/5/3/137/142310
| Introduction|| |
Glycogenosis II [Glycogen storage Disease type II (GSDII); Pompe disease] is an autosomal recessive lysosomal storage disorder due to deﬁciency of acid alpha-glucosidase resulting in lysosomal accumulation of glycogen in skeletal, cardiac and smooth muscle, with progressive motor, cardiac and respiratory failure.  Although the pathological process mainly affects muscles, several other tissues may be involved in the course of the disease; therefore GSD II should be regarded as a multisystem disorder also involving liver, spleen, salivary glands, kidney, bone and blood vessels. , Craniovertebral junction (CVJ) malformations have never been reported so far in GSDII patients.
We here report a GSDII patient who recurrently suffered from headache, neck pain and dizziness which were likely related to a very rare complex CVJ malformation.
| Case description|| |
We describe the case of a 43-year-old woman affected with GSDII who harbored the mutations IVS1-13T>G and c.2237G>A in the acid alpha-glucosidase gene. The onset of symptoms was at the age of 16 with difﬁculty in climbing stairs and standing up from the floor. Her neurological examination showed anserine gait, proximal muscle weakness especially of lower limbs, and mild eyelid ptosis.
Since several years she suffered from persistent neck pain, dizziness and headache that greatly affect her quality of life. In order to investigate these symptoms, she was submitted to brain MRI and cervical spine CT scan with selective study of skull occipital junction.
Neuroimaging showed a rare complex CVJ malformation composed of basilar invagination, basiocciput hypoplasia, partial C1 assimilation, C1 posterior arch hypoplasia, C1 lateral mass hypoplasia and offset [Figure 1]. Measurement tools used to assess the diagnosis were Chamberlain line, Wackenheimclivus baseline and atlanto-occipital joint axis angle. 
|Figure 1: Cervical spine CT scan: (a) Coronal view showing posterior C1 arch partial assimilation and hypoplasia, (b) Sagittal view showing basiocciput hypoplasia and basilar invagination, (c) Coronal view showing C1 right lateral mass hypoplasia and articular offset|
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| Discussion|| |
The bony CVJ is an articulation point capable of complex motions distinct from the remainder of the vertebral column. It can be conceptually divided into two components with respect to the governance of intersegmental movements.  The first component mainly consists of a central pivot made up of the dens and the C2 vertebral body. However, the basiocciput, though anatomically part of the foramen magnum, is embryologically and functionally in vertical linearity with the dens and is thus part of the central pillar. The second component consists of two ringed structures surrounding the central pivot, albeit eccentrically. They are the foramen magnum ring (comprising the lateral portion of the basiocciput and the exocciput including the occipital condyles and the opisthion) and the atlantal ring with its anterior and posterior arches and lateral masses.
Hox and Pax genes are involved in the regulation of CVJ development.  Hox genes control the body plan of the embryo along the anterior-posterior axis. Following primary segmentation, they determine the positional identity of the pre-vertebral segments and the vertebral phenotypes (types of vertebrae that will form on different segments). Pax gene family is important in early development for the specification of specific tissues and is implicated in sclerotomalresegmentation.
The malformation found in our patient involves both the components of CVJ, including basiocciput and atlantal ring, and it is likely to give rise to neck pain, dizziness and headache by altering the complex motion function of this region.
The correlation between CVJ malformation, Hox and Pax gene families and GSDII in this patient remains unknown and we cannot reasonably rule out the incidental co-occurrence of the two conditions. However, the rarity of this malformation as well as the well-known GSDII propensity to multisystem involvement (i.e. brain abnormalities, bone mineral density alterations, rigid spine, large vessel malformations, hemangiomas) ,,,, makes intriguing the idea of a possible relationship, thus suggesting to study the CVJ in the diagnostic process of GSDII patients in order to assess the CVJ malformation frequency in GSDII population.
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