40 Horizonal gaze palsy with progressive scoliosis secondary to ROBO3 gene variants associated with osteogenesis imperfecta type I

• Published in: Archives of disease in childhood 2023-02, Vol.108 (Suppl 1), p.A15-A15
• Main Authors: Crowe, Belinda, Bowman, Richard, Löbel, Ulrike, Calder, Alistair, Gibson, Alexander, Allgrove, Jeremy, DeVile, Catherine
• Format: Article
• Language: English
• Subjects: Age; Anatomy; Brain stem; Cell migration; Collagen (type I); Compression; Digital posters; Eye Movements; Femur; Fractures; Genetic screening; Genotypes; Hereditary diseases; Heterozygosity; Hypoplasia; Medulla oblongata; Myopia; Nervous system; Neuroimaging; Osteogenesis; Osteogenesis imperfecta; Paralysis; Pediatrics; Phenotypes; Scoliosis; Thorax; Torticollis; Vertebrae; Vision
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2023-gosh.40

BackgroundHorizontal gaze palsy with progressive scoliosis (HGPPS) is a rare autosomal recessive neurological disorder characterised by absence of conjugate horizontal eye movements and early-onset rapidly progressive scoliosis. It is caused by variants in ROBO3, essential for axon decussation and contralateral neuronal migration during nervous system development. We describe a unique case of HGPPS and bone fragility.Presenting ProblemA 19-month-old girl with genetically confirmed osteogenesis imperfecta (OI) type I presented to our OI Service, following intramedullary rod insertion for a femur fracture aged 16 months. Her Romanian family have mild OI, secondary to COL1A1 heterozygosity. Parents are non-consanguineous. Our assessment identified abnormal visual behaviour, horizontal gaze palsy, left torticollis and a flexible thoracic dextroconvex scoliosis. Ophthalmological assessment confirmed horizontal gaze palsy, finding significant myopia with astigmatism, anisometropia and reduced left ocular vision. ROBO3 gene testing was initiated. Neuroimaging revealed brainstem malformation with pontine hypoplasia, absent facial colliculi, butterfly configuration of the medulla and a deep midline pontine cleft in keeping with HGPPS.Clinical ManagementTo promote vision glasses were prescribed. Aged 26 months scoliosis had progressed, with a levoconvex thoracolumbar component; T9-L5 Cobb angle 38°. By 32 months this progressed further; dextroconvex T2-T11 Cobb angle 45°, levoconvex T10-L4 Cobb angle 66°. This rapidly progressive scoliosis was atypical for mild OI – she had no vertebral compression fractures. Given concerns regarding rigid spinal bracing in OI a Lycra suit was provided. Multidisciplinary input including physiotherapy, spinal orthopaedic and ophthalmological monitoring is ongoing. Aged 35 months genetic results confirmed compound heterozygosity for two ROBO3 variants.DiscussionThorough clinical assessment and genotype-phenotype correlation is essential in children with known familial gene variants. When atypical clinical features present additional diagnoses should be sought. For children with dual diagnoses specialist multidisciplinary input is required to optimally manage comorbidities and achieve best possible developmental outcomes.