Diencephalic syndrome in child with NF-1 and hypothalamic tumour

We describe a 20 month old boy with neuro-fibromatosis type 1 (NF-1) who presented with diencephalic syndrome due to a large hypothalamic tumour and developed massive necrosis after chemotherapy associated with severe encephalopathy. We report this case because of rapid progression of presenting symptoms, the rare association with diencephalic syndrome in NF-1, chemotherapy induction of “tumour lysis” associated with encephalopathy, reduced toxicity and sustained improvement with vinblastine, the therapeutic benefit of tumour drainage signs of resolution of diencephalic syndrome and then restoration of visual movements and function associated with developmental recovery. The presentation of tumour in this case highlights the importance for parents and doctor to known and recognize the precocious symptoms, and justifies sharing these features as an indicator with parents and GP’s to justify early / urgent specialist review, particularly in the first two years of life. Early recognition could offer a reduced risk of brain injury

Neuropsychological outcomes of children with Optic Pathway Glioma

Optic Pathway Glioma (OPG) is a relatively common brain tumour in childhood; however, there is scarce understanding of neuropsychological sequelae in these survivors. In this study, 12 children with diagnosis of OPG before 6 years of age received a comprehensive standardised assessment of visual perception, general intelligence and academic achievement, using adjustments to visual materials of the tests, to examine the extent of concurrent impairment in these functional domains. Information about vision, clinical and sociodemographic factors were extracted from medical records to assess the associations of neuropsychological outcomes with clinical and socio-demographic factors. Children with OPG exhibited high within-patient variability and moderate group-level impairment compared to test norms. Visual perception was the most impaired domain, while scholastic progression was age-appropriate overall. For cognition, core verbal and visuo-spatial reasoning skills were intact, whereas deficits were found in working memory and processing speed. Visual function was associated with tasks that rely on visual input. Children with OPG are at moderate risk of neuropsychological impairment, especially for visual perception and cognitive proficiency. Future research should elucidate further the relative contribution of vision loss and neurofibromatosis type 1 co-diagnosis within a large sample

Diencephalic syndrome in child with NF-1 and hypothalamic tumour

We describe a 20 month old boy with neuro-fibromatosis type 1 (NF-1) who presented with diencephalic syndrome due to a large hypothalamic tumour and developed massive necrosis after chemotherapy associated with severe encephalopathy.We report this case because of rapid progression of presenting symptoms, the rare association with diencephalic syndrome in NF-1, chemotherapy induction of “tumour lysis” associated with encephalopathy, reduced toxicity and sustained improvement with vinblastine, the therapeutic benefit of tumour drainage signs of resolution of diencephalic syndrome and then restoration of visual movements and function associated with developmental recovery. The presentation of tumour in this case highlights the importance for parents and doctor to known and recognize the precocious symptoms, and justifies sharing these features as an indicator with parents and GP’s to justify early / urgent specialist review, particularly in the first two years of life. Early recognition could offer a reduced risk of brain injury

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus

Idiopathic congenital nystagmus (ICN) is characterised by involuntary, periodic, predominantly horizontal, oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 ICN singleton cases (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina suggesting a specific role in the control of eye movement and gaze stability

Phenotyping and Genotyping of Idiopathic Infantile Nystagmus

Background: Nystagmus can be a manifestation of ocular or systemic disorders. However, it may represent a separate disease entity by itself as in idiopathic infantile nystagmus (IIN). In 2004, Kerrison et al. localised the gene causing X-linked IIN to Xq26-27 (NYS1); however, the gene/genes causing IIN had not been identified. Aims and Objectives: The aims of this study were threefold. 1. To ascertain families and singletons (sporadic subjects) with IIN. 2. To further refine the locus NYS1 and to identify the gene causing X-linked IIN 3. To describe and compare the phenotype of subjects with IIN Methods: 39 families and 78 singletons with nystagmus were recruited and phenotyped. Genotyping with microsatellite markers were performed in the X-linked families to refine the genetic interval at Xq26-27. Gene sequencing was carried out by our collaborators (not by the author) at the Sanger Institute. The clinical features and eye movement recordings of 90 subjects with mutations in the FRMD7 gene were compared to 48 subjects with IIN not associated with mutations in this gene (non-FRMD7 group). Results: I: 149 familial subjects and 78 sporadic subjects with IIN were phenotyped. 121 subjects from 30 families were diagnosed to have X-linked IIN while 28 subjects from 9 families had other diagnosis such as albinism and aniridia. II: Genetic mapping in 16 families with X-linked IIN, refined the critical interval at Locus NYS1 (Xq26-17) to a 9mB region between markers DXS8072 and DXS8094 which contained about 80 genes. High throughput DNA sequencing was carried out at the Sanger Institute which led to the discovery of FRMD7, mutations in which is associated with X-linked IIN. III: The median visual acuity in subjects with a FRMD7 mutation was log MAR 0.301. The number of subjects with good stereopsis (Lang positive) was higher in the FRMD7 group (93.4%) compared to subjects in the non- FRMD7 group (78.4%). None of the subjects in the FRMD7 group had severe (>15˚) anomalous head posture (AHP) while 27% of subjects in the non-FRMD7 group had AHP more than 15˚. 52.17% of obligate female carriers of a FRMD7 mutation were clinically affected. Discussion: This study identified the first gene causing idiopathic infantile nystagmus. The phenotypic characteristics of these subjects will help in clinically identifying subjects with IIN due to mutations in FRMD7. In addition it has generated a stage for further research into the mechanisms behind ocular motor control

Phenotyping and genotyping of idiopathic infantile nystagmus

Background: Nystagmus can be a manifestation of ocular or systemic disorders. However, it may represent a separate disease entity by itself as in idiopathic infantile nystagmus (IIN). In 2004, Kerrison et al. localised the gene causing X-linked IIN to Xq26-27 (NYS1); however, the gene/genes causing IIN had not been identified. Aims and Objectives: The aims of this study were threefold. 1. To ascertain families and singletons (sporadic subjects) with IIN. 2. To further refine the locus NYS1 and to identify the gene causing X-linked IIN 3. To describe and compare the phenotype of subjects with IIN Methods: 39 families and 78 singletons with nystagmus were recruited and phenotyped. Genotyping with microsatellite markers were performed in the X-linked families to refine the genetic interval at Xq26-27. Gene sequencing was carried out by our collaborators (not by the author) at the Sanger Institute. The clinical features and eye movement recordings of 90 subjects with mutations in the FRMD7 gene were compared to 48 subjects with IIN not associated with mutations in this gene (non-FRMD7 group). Results: I: 149 familial subjects and 78 sporadic subjects with IIN were phenotyped. 121 subjects from 30 families were diagnosed to have X-linked IIN while 28 subjects from 9 families had other diagnosis such as albinism and aniridia. II: Genetic mapping in 16 families with X-linked IIN, refined the critical interval at Locus NYS1 (Xq26-17) to a 9mB region between markers DXS8072 and DXS8094 which contained about 80 genes. High throughput DNA sequencing was carried out at the Sanger Institute which led to the discovery of FRMD7, mutations in which is associated with X-linked IIN. III: The median visual acuity in subjects with a FRMD7 mutation was log MAR 0.301. The number of subjects with good stereopsis (Lang positive) was higher in the FRMD7 group (93.4%) compared to subjects in the non- FRMD7 group (78.4%). None of the subjects in the FRMD7 group had severe (>15˚) anomalous head posture (AHP) while 27% of subjects in the non-FRMD7 group had AHP more than 15˚. 52.17% of obligate female carriers of a FRMD7 mutation were clinically affected. Discussion: This study identified the first gene causing idiopathic infantile nystagmus. The phenotypic characteristics of these subjects will help in clinically identifying subjects with IIN due to mutations in FRMD7. In addition it has generated a stage for further research into the mechanisms behind ocular motor control.EThOS - Electronic Theses Online ServiceGBUnited Kingdo