Objective: To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on ...Objective: To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems. Methods: The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies. Results: Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected. Conclusions: The major clinical characteristics of horizontal gaze palsy and progressive scoliosiswere congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.展开更多
Horizontal Gaze Palsy with Progressive Scoliosis is a rare, congenital autosomal recessive disorder caused by mutations in the ROBO3 gene. It is characterized by the absence of conjugate horizontal eye movements with ...Horizontal Gaze Palsy with Progressive Scoliosis is a rare, congenital autosomal recessive disorder caused by mutations in the ROBO3 gene. It is characterized by the absence of conjugate horizontal eye movements with preserved vertical gaze, variable convergence, and progressive scoliosis, developing in childhood and adolescence. ROBO3 gene mutations are causative of the lack, or at least reduction, of crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. To date, 39 different mutations, including missense, nonsense, frameshift, and splice site mutations have been described in the ROBO3 gene and related to Horizontal Gaze Palsy With Progressive Scoliosis. In addition, a lot of variants of uncertain pathological significance have been reported for the first time by Illumina Clinical Services. Here we report an update on mutations of the ROBO3 gene and some information on the pathogenesis but much remains to be investigated on the consequences of mutations on ROBO3 expression and function. Therefore, further detailed functional analyses are necessary to clarify a possible role of the variants of uncertain pathological significance as the cause of the disease. In conclusion, we hope that this article will help in molecular screening for the ROBO3 gene and will contribute to enlargement of the ROBO3 gene variation database.展开更多
文摘Objective: To review the neurologic, neuroradiologic, and electrophysiologic features of autosomal recessive horizontal gaze palsy and progressive scoliosis (HGPPS), a syndrome caused by mutation of the ROBO3 gene on chromosome 11 and associated with defective decussation of certain brainstem neuronal systems. Methods: The authors examined 11 individuals with HGPPS from five genotyped families with HGPPS. Eight individuals had brain MRI, and six had electrophysiologic studies. Results: Horizontal gaze palsy was fully penetrant, present at birth, and total or almost total in all affected individuals. Convergence, ocular alignment, congenital nystagmus, and vertical smooth pursuit defects were variable between individuals. All patients developed progressive scoliosis during early childhood. All appropriately studied patients had hypoplasia of the pons and cerebellar peduncles with both anterior and posterior midline clefts of the pons and medulla and electrophysiologic evidence of ipsilateral corticospinal and dorsal column-medial lemniscus tract innervation. Heterozygotes were unaffected. Conclusions: The major clinical characteristics of horizontal gaze palsy and progressive scoliosiswere congenital horizontal gaze palsy and progressive scoliosis with some variability in both ocular motility and degree of scoliosis. The syndrome also includes a distinctive brainstem malformation and defective crossing of some brainstem neuronal pathways.
文摘Horizontal Gaze Palsy with Progressive Scoliosis is a rare, congenital autosomal recessive disorder caused by mutations in the ROBO3 gene. It is characterized by the absence of conjugate horizontal eye movements with preserved vertical gaze, variable convergence, and progressive scoliosis, developing in childhood and adolescence. ROBO3 gene mutations are causative of the lack, or at least reduction, of crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. To date, 39 different mutations, including missense, nonsense, frameshift, and splice site mutations have been described in the ROBO3 gene and related to Horizontal Gaze Palsy With Progressive Scoliosis. In addition, a lot of variants of uncertain pathological significance have been reported for the first time by Illumina Clinical Services. Here we report an update on mutations of the ROBO3 gene and some information on the pathogenesis but much remains to be investigated on the consequences of mutations on ROBO3 expression and function. Therefore, further detailed functional analyses are necessary to clarify a possible role of the variants of uncertain pathological significance as the cause of the disease. In conclusion, we hope that this article will help in molecular screening for the ROBO3 gene and will contribute to enlargement of the ROBO3 gene variation database.
