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 Table of Contents  
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 250-254

Scoliosis associated with HGPPS syndrome: What do we know?

1 Bharati Vidyapeeth Medical College, Dhankawadi, Pune, Maharashtra, India
2 Sparsh Hospital, Bengaluru, Karnataka, India

Date of Submission07-Feb-2021
Date of Acceptance30-Apr-2021
Date of Web Publication16-Jul-2021

Correspondence Address:
Naveen S Tahasildar
Sparsh Hospital, 29/P2, The Health City, Bommasandra Industrial Area, Hosur Road, Bengaluru 560099, Karnataka.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ISJ.ISJ_17_21

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Horizontal gaze palsy with progressive scoliosis (HGPPS) syndrome is a rare genetic abnormality causing cranial dysinnervation manifesting as absence of conjugate lateral eye movements, nystagmus, and scoliosis. While the genetics, imaging abnormalities, and ocular manifestations have been well described in literature, the spinal deformity has not been addressed adequately. An 11-year-old girl presented with progressive thoracic scoliosis who on evaluation was detected to have all the features of HGPPS syndrome. The patient underwent posterior correction of scoliosis uneventfully. A thorough literature search was performed to understand the descriptors of spinal deformity and its surgery in HGPPS syndrome. The spinal deformity in HGPPS resembles adolescent idiopathic scoliosis. Rapidly progressive right thoracic scoliosis was the usual pattern. Surgical and anesthetic considerations during surgery are similar to idiopathic scoliosis. These children tolerate surgery and anesthesia well. Neuromonitoring changes during surgery need to be interpreted correctly in the background of uncrossed sensory and motor tracts.

Keywords: Congenital cranial dysinnervation disorders, HGPPS syndrome, intra-operative neuromonitoring, scoliosis, spinal deformity

How to cite this article:
Menon V, Tahasildar NS, Sivaraman T, Venkateshappa BM. Scoliosis associated with HGPPS syndrome: What do we know?. Indian Spine J 2021;4:250-4

How to cite this URL:
Menon V, Tahasildar NS, Sivaraman T, Venkateshappa BM. Scoliosis associated with HGPPS syndrome: What do we know?. Indian Spine J [serial online] 2021 [cited 2021 Dec 4];4:250-4. Available from: https://www.isjonline.com/text.asp?2021/4/2/250/321560

  Introduction Top

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare genetic disorder characterized by the absence of conjugate horizontal eye movements, preservation of vertical gaze, and convergence, caused by mutations in the ROBO3 gene.[1] There is extensive literature on neural tract defects and genetics but spinal deformity has not been studied in detail. The authors present a case of HGPPS syndrome with special reference to anesthetic and intra-operative neuromonitoring issues we encountered and the post-operative course. Literature evidence about the spinal deformity is also elaborated.

  Case Report Top

An 11-year-old girl with thin built came with rapidly progressive scoliosis causing a gross cosmetic deformity, significant trunk imbalance, and substantial rib hump [Figure 1]. She also had titubations and nystagmus. Pulmonary Function Test (PFT) showed mild restrictive airway disease and arterial blood gas revealed mild hypoxemia. Her X-rays revealed a right thoracic scoliosis from D6 to L1 measuring 78° Cobb correcting to only 64° (stiff curve) on side bending radiographs [Figure 2]. Although spinal magnetic resonance imaging (MRI) scan revealed no abnormality, MRI brain demonstrated hypoplasia of the pons and medulla with the characteristic split pons sign and butterfly morphology of the medulla suggestive of HGPPS syndrome [Figure 3] and [Figure 4]. The fourth ventricle was flattened and resembled a tent at the level of pons.
Figure 1: Clinical photograph of the child depicting significant scoliosis and rib hump

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Figure 2: Standing AP and Lateral Xrays along with Side Bending radiographs. Note idiopathic scoliosis like curve location, hypokyphosis, and vertebral rotation around the apex

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Figure 3: MRI images (axial sections) through the brain stem. The butterfly-shaped medulla, longitudinally split pons, and the tenting of the fourth ventricle are demonstrated

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Figure 4: The sagittal MR image shows the low volume pons and medulla and the tented fourth ventricle. The axial section depicts the coronal split in the brain stem

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Under anesthesia, the patient was positioned prone, and baseline readings of intraoperative neuromonitoring (SSEP, MEP, unprocessed EEG) were recorded. T4 to L3 instrumentation along with peri-apical Ponte’s osteotomies was done to achieve a good correction using standard operative maneuvers. The neuromonitoring was uneventful [Figure 5] even though two screws needed reinsertion due to misplacement. Decortication and fusion were done using local and synthetic graft.
Figure 5: IONM data of the case illustrating the measured parameters: SSEP and TcMEP

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  Discussion Top

HGPPS is a rare congenital cranial dysinnervation disorder occurring worldwide, typically in consanguineous families, though sporadic incidence has also been reported. Crisfield[2] is credited with the first report of four patients with progressive scoliosis and external ophthalmoplegia in 1974. Sharpe et al.[3] in 1975 described the classical triad of paralysis of horizontal gaze, pendular nystagmus, and progressive scoliosis with a typical recessive inheritance pattern. By early 2000s, several studies on the genetics of HGPPS syndrome appeared, with Jen et al.[1] mapping out the disease locus to a 30-cM interval on chromosome 11q23–25 (mutation in the region of ROBO3). This results in failure of some axonal pathways in the central nervous system that would normally cross over during embryonic development. Genetic transmission is typically autosomal recessive. The only consistently inherited form of congenital horizontal gaze palsy is when it is co-inherited with progressive scoliosis. The European Neuromuscular Center in 2002 named CCDDs (Congenital Cranial Dysinnervation Disorders) was formed to include a variety of conditions with discrete phenotypes and genetic anomalies.

The last decade saw a host of studies describing the imaging anatomy of the brain and delineating the structural defects therein. The structural defects in the brain and brain stem are revealed by MRI, diffusion tensor imaging (DTI), and tractographic images, which show the characteristic anterior and posterior midline clefts. The anterior cleft at the medullary level accompanied by the anteriorly flattened medulla gives a butterfly-like appearance on axial sections, as seen in our case. The pons is often flattened, and the facial colliculi does not protrude into the fourth ventricle. DTI and MR tractography reveal ipsilateral ascending and descending tracts without crossing over, although normal inter-hemispheric connections in the corpus callosum were demonstrable in some studies.[4]

The pattern of spinal deformity in HGPPS syndrome is largely deduced based on individual cases reported by different authors across different continents. The scoliosis is described as rapidly progressive and can be detected as early as the first few months of life (Kurian et al.[5] described a case at 18 months) but is typically diagnosed by mid-childhood. Volk et al.[6] suggest that the deformity manifests after two years and progresses within the first decade. Asymptomatic patients often report in late adulthood when vision is compromised by cataract or other disorders. The deformity recorded in most reports is right thoracic or thoracolumbar. Typically, these children do not respond to bracing or physiotherapy, and the curve often exceeds 70° Cobb. No underlying pathology of muscle, spinal cord, or spine has been detected, and the defect seems to most closely mimic idiopathic scoliosis. These authors have also noted significant rib hump, thoracic lordosis, and trunk rotation as in Adolescent Idiopathic Scoliosis (AIS) patients with severe curve types. We planned surgery similar to idiopathic scoliosis, although literature does not provide any strategy for spinal deformity correction in HGPPS patients. Though the radiographic abnormalities in the brain stem did raise certain apprehensions, the Intra-operative Neuromonitoring (IONM) baselines and the monitoring during surgery were uneventful. Samoladas et al.[7] also reported normal IONM studies akin to our report. Jen et al.’s[1] study did demonstrate that the ascending and descending spinal tracts do not cross over on neurophysiologic studies in patients with axon guidance anomalies of the neural system. Amoiridis et al.[8] have reported that electrophysiological studies show both crossed and uncrossed tracts in HGPPS cases. Haller et al.[9] have also recorded that SSEPs and MEPs can detect the uncrossed sensory and motor spinal tracts, and these appear to be partial and often asymmetric in their patients. From a surgical perspective, this is important to consider because confusion might arise if this is not recognized pre-operatively. MacDonald et al.[10] did indeed describe such a case in which non-decussation was discovered accidentally during scoliosis surgery. The case reported here had a normal post-operative recovery, and at one year’s review, she maintained correction and excellent cosmetic result [Figure 6].
Figure 6: Post-operative clinical photograph and radiographs demonstrating the correction achieved during surgery for scoliosis

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  Conclusion Top

Patients with HGPPS can be expected to have normal anesthesia and surgery for their scoliosis despite the large, rapidly progressive, stiff spinal deformity. Nonetheless, one needs to be aware of the uncrossed spinal tracts to avoid confusion during IONM recording. The post-operative results from the scoliosis surgery are similar to those of adolescent idiopathic scoliosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rüb U, et al. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 2004;304:1509-13.  Back to cited text no. 1
Crisfield RJ. Scoliosis with progressive external ophthalmoplegia in four siblings. J Bone Joint Surg Br 1974;56B:484-9.  Back to cited text no. 2
Sharpe JA, Silversides JL, Blair RD. Familial paralysis of horizontal gaze. Associated with pendular nystagmus, progressive scoliosis, and facial contraction with myokymia. Neurology 1975;25:1035-40.  Back to cited text no. 3
Sicotte NL, Salamon G, Shattuck DW, Hageman N, Rüb U, Salamon N, et al. Diffusion tensor MRI shows abnormal brainstem crossing fibers associated with ROBO3 mutations. Neurology 2006;67:519-21.  Back to cited text no. 4
Kurian M, Megevand C, De Haller R, Merlini L, Boex C, Truffert A, et al. Early-onset or rapidly progressive scoliosis in children: Check the eyes! Eur J Paediatr Neurol 2013;17:671-5.  Back to cited text no. 5
Volk AE, Carter O, Fricke J, Herkenrath P, Poggenborg J, Borck G, et al. Horizontal gaze palsy with progressive scoliosis: Three novel ROBO3 mutations and descriptions of the phenotypes of four patients. Mol Vis 2011;17:1978-86.  Back to cited text no. 6
Samoladas EP, O’Dowd J, Cardoso-Almeida A, Demetriades AK. Horizontal gaze palsy and scoliosis: A case report and review of the literature. Hippokratia 2013;17:370-2.  Back to cited text no. 7
Amoiridis G, Tzagournissakis M, Christodoulou P, Karampekios S, Latsoudis H, Panou T, et al. Patients with horizontal gaze palsy and progressive scoliosis due to ROBO3 E319K mutation have both uncrossed and crossed central nervous system pathways and perform normally on neuropsychological testing. J Neurol Neurosurg Psychiatry 2006;77:1047-53.  Back to cited text no. 8
Haller S, Wetzel SG, Lütschg J. Functional MRI, DTI and neurophysiology in horizontal gaze palsy with progressive scoliosis. Neuroradiology 2008;50:453-9.  Back to cited text no. 9
MacDonald DB, Streletz LJ, Al-Zayed Z, Abdool S, Stigsby B. Intraoperative neurophysiologic discovery of uncrossed sensory and motor pathways in a patient with horizontal gaze palsy and scoliosis. Clin Neurophysiol 2004;115:576-82.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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