Genetically confirmed horizontal gaze palsy with progressive scoliosis syndrome diagnosed at 8 months before the development of scoliosis: a case report

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a very rare autosomal recessive syndrome due to biallelic mutations in ROBO3 gene. HGPPS is defined by congenital deficiency of conjugated horizontal eye movements and development of progressive scoliosis. Some patients are diagnosed with this condition before the onset of scoliosis. An 8-month-old male infant, born from parents with no consanguinity, was referred for inability to track moving targets. The patient presented with bilateral horizontal gaze palsy without any involvement of vertical gaze, intact pupil responses and without presence of ptosis, nystagmus, facial weakness and spinal deformity. Magnetic Resonance Imaging (MRI) revealed pontine hypoplasia with midline pontine cleft (“split pons” sign) and butterfly appearance of the medulla, while spinal MRI demonstrated normal anatomy. The molecular genetic testing using targeted next-generation sequencing revealed a homozygous nonsense mutation in ROBO3 gene, ROBO3 NM_022370.3:c.1450C > T (p.Arg484Ter), which was considered as a pathogenic variant according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) criteria (PVS1, PM2_Supporting, PP4 [reported by the lab as being pathogenic]). Both parents carried heterozygous mutation. After 12 months since first visit (20 months old) the patient presented unchanged horizontal gaze palsy and no scoliosis. In a child with congenital HGPPS, specific MRI brainstem features should lead to ROBO3 genetic testing, even in the absence of spinal involvement. This case provides a rare homozygous nonsense mutation that has not been described before in either population genetic databases or ClinVar. The follow-up period is short, and scoliosis may yet occur.