Visual Function in Noonan and LEOPARD Syndrome

Abstract

The aim of the study was to assess various aspects of visual and visuoperceptual function in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) with mutations affecting the PTPN11, SOS1 and RAF1 genes. Twenty-four patients were assessed with a battery of tests assessing visual function including ophthalmological and orthoptic evaluation and age appropriate behavioural visual tests, including measures of crowding acuity (Cambridge crowding cards), and stereopsis (TNO test). Twenty-one subjects were also assessed with the visuo-motor integration (VMI) test. Twenty of the 24 patients (83%) had abnormalities of visual function on at least one of the tests used to assess visual function or on ophthalmological examination, and 7 of 21 (33%) also had abnormalities on VMI. Ocular movements and stereopsis were most frequently abnormal (50% and 79%, respectively). Our results suggest that visual and visuoperceptual abilities are commonly impaired in patients with Noonan and LEOPARD syndrome and they are probably related to a multifactorial etiology.

vision - Noonan syndrome - LEOPARD syndrome - genotype-phenotype

References

• 1 Allanson JE. Noonan syndrome.  Am J Med Genet C Semin Med Genet. 2007;  145 274-279
• 2 Atkinson J. Review of human visual development: crowding and dyslexia. In: Stein JF, ed. Vision and visual dyslexia (Vol. 13 of Vision and visual dysfunction edited by Cronly-Dillon JR). New York: MacMillan Press 1991: 44-57
• 3 Atkinson J, van Hof-van Duin J. Visual assessment during the first years of life. In: Fielder A, Bax M, eds. Management of visual impairment in childhood. London: MacKeith Press 1993
• 4 Carta C, Pantaleoni F, Bocchinfuso G. et al . Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype.  Am J Hum Genet. 2006;  79 129-135
• 5 Cesarini L, Alfieri P, Pantaleoni F. et al . Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade.  Am J Med Genet, in press.
• 6 Jongmans M, Mercuri E, Henderson S. et al . Visual function of prematurely born children with and without perceptual-motor difficulties.  Early Hum Dev. 1996;  45 73-82
• 7 Beery KE. Administration, scoring, and teaching manual for the Beery-Buktenica developmental test of visual-motor integration with supplemental tests of visual perception and motor coordination. Modern Curriculum Press, New Jersey 1997
• 8 Lee DA, Portnoy S, Hill P. et al . Psychological profile of children with Noonan syndrome.  Dev Med Child Neurol. 2005;  47 35-38
• 9 Lee NB, Kelly L, Sharland M. Ocular manifestations of Noonan syndrome.  Eye. 1992;  6 328-334
• 10 Noonan JA. Noonan syndrome. An update and review for the primary pediatrician.  Clin Pediatr (Phila). 1994;  33 548-555
• 11 Okuda FC, Apt L, Wanters BS. Evaluation of the TNO random-dot stereogram.  Am Orthoptic J. 1977;  34 124-131
• 12 Pandit B, Sarkozy A, Pennacchio LA. et al . Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.  Nat Genet. 2007;  39 1007-1012
• 13 Pike MG, Holstrom G, de Vries L. et al . Pattern of visual impairment associated with lesions of the preterm infant brain.  Dev Med Child Neurol. 1994;  36 849-862
• 14 Sarkozy A, Digilio MC, Zampino G. et al .LEOPARD syndrome: clinical aspects and molecular pathogenesis. In: Zenker M, ed. Monographs in Human Genetics – Vol. 17. Noonan syndrome and related disorders: A matter of deregulated RAS signaling. Karger Press, Basel, in press 2008
• 15 Sarkozy A, Digilio MC, Marino B. et al .Genotype-phenotype correlations in Noonan syndrome. In: Zenker M, ed Monographs in Human Genetics – Vol. 17 Noonan syndrome and related disorders: A matter of deregulated RAS signaling. Karger Press, Basel, in press 2008
• 16 Tartaglia M, Kalidas K, Shaw A. et al . PTPN11 mutations in Noonan syndrome. Molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.  Am J Hum Genet. 2002;  70 1555-1563
• 17 Tartaglia M, Gelb BD. Noonan syndrome and related disorders: genetics and pathogenesis.  Annu Rev Genomics Hum Genet. 2005;  6 45-68
• 18 Tartaglia M, Pennacchio L, Zhao C. et al . Gain-of-function SOS1 mutations cause a distintive form of Noonan syndrome.  Nat Genet. 2007;  39 75-79
• 19 Tartaglia M, Gelb BD. Molecular genetics of Noonan syndrome. In: Zenker M, ed. Monographs in Human Genetics – Vol. 17. Noonan syndrome and related disorders: A matter of deregulated RAS signaling. Karger Press, Basel, in press 2008
• 20 Van der Burgt I, Berends E, Lommen E. et al . Clinical and molecular studies in a large Dutch family with Noonan syndrome.  Am J Med Genet. 1994;  53 187-191
• 21 Verhoeven W, Wingbermühle E, Egger J. et al . Noonan syndrome: psychological and psychiatric aspects.  Am J Med Genet A. 2008;  146 191-196
• 22 Voron DA, Hatfield HH, Kalkhoff RK. Multiple lentigines syndrome. Case report and review of the literature.  Am J Med. 1976;  60 447-456

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