Learn about Horizontal gaze palsy with progressive scoliosis
Horizontal gaze palsy with progressive scoliois (HGPPS) is a rare recessive Congenital Cranial Dysinnervation Disorder that has been reported in several dozen consanguineous families (related by blood) of Greek1-4, Japanese5,6, Chinese7,8, Israeli9, North American10-12, Dutch13, Italian14,15, German16-18, Asian19, Saudi Arabian20, and Indian20 descent.
Horizontal Gaze Palsy is rarely reported in isolation and may be diagnosed as Duane Syndrome Type III. Horizontal gaze palsy together with facial weakness is classified as Moebius syndrome. The only consistently inherited form of congenital Horizontal gaze palsy is when it is co-inherited with progressive scoliosis.
Individuals with HGPPS are born with no horizontal eye movements and develop scoliosis (curvature of the spine) as infants or children. Vertical eye movements are typically normal.
The progressive thoracic scoliosis found in individuals with HGPPS can be detected as early as the first months of life and is typically diagnosed by mid-childhood. No underlying pathology of muscle, spinal cord, or spine has been detected and the defect seems to most closely mimic idiopathic scoliosis.
In 2002 Jen et al20 reported identification of two HGPPS pedigrees residing in Saudi Arabia, one of Saudi and one of Indian descent. Homozygosity mapping using a 10 cM genome-wide scan revealed a 30 cM homozygous region in all six affected individuals on chromosome 11q23-q25.
In collaboration with Joanna Jen and researchers at UCLA we identified 8 additional HGPPS families located in Saudi Arabia, Turkey, Greece, Pakistan and Italian that mapped or reduced to homozygosity in the HGPPS critical region. We then went on to identify missense, nonsense, frameshift, and splicing mutations in the axon guidance molecule gene, ROBO3, in all ten HGPPS families21. Results of neuroimaging and neurophysiology studies undertaken on HGPPS participants found that the axons that make up the major motor and sensory pathways for communication between the brain and the body fail to cross the midline in the hindbrain of these individuals.
Please contact Caroline Andrews to obtain further information on the genetic studies that we are undertaking and if you are interested in enrolling a patient or participating yourself.
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor, Johns Hopkins University, last updated 6/23/2004 (entry number #607313). Home page: http://www3.ncbi.nlm.nih.gov/Omim/.
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- Jen, J. et al. Familial horizontal gaze palsy with progressive scoliosis maps to chromosome 11q23-25. Neurology 59, 432-5 (2002).
- Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rub U, Shattuck D, Salamon G, Kudo LC, Ou J, Lin DD, Salih MA, Kansu T, Al Dhalaan H, Al Zayed Z, MacDonald DB, Stigsby B, Plaitakis A, Dretakis EK, Gottlob I, Pieh C, Traboulsi EI, Wang Q, Wang L, Andrews C, Yamada K, Demer JL, Karim S, Alger JR, Geschwind DH, Deller T, Sicotte NL, Nelson SF, Baloh RW, Engle EC. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science. 2004 Jun 4;304(5676):1509-13. Epub 2004 Apr 22.