- Email: [email protected]
Bilateral anterior lens dislocation: the genetic perspective – Authors' reply
Correspondence
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Forouzanfar MH, Foreman KJ, Delossantos AM, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011; 378: 1461–84. Institute for Health Metrics and Evaluation. The challenge ahead: progress and setbacks in breast and cervical cancer. Seattle: IHME, 2011. http://www.healthmetricsandevaluation.org/ publications/policy-report/challenge-aheadprogress-and-setbacks-breast-and-cervicalcancer (accessed March 27, 2012). International Agency for Research on Cancer, World Health Organization. GLOBOCAN: data sources and methods. http://globocan.iarc.fr/ (accessed Sept 23, 2011).
Department of Genetics, Institute of Liver and Biliary Sciences, New Delhi, India 1
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Bilateral anterior lens dislocation: the genetic perspective
Science Photo Library
Jagat Ram and colleagues (Oct 15, p 1501)1 describe an infant with bilateral spherophakia, megalocornea, and anterior lens dislocation, and report the systemic examination as being normal. I hope a genetic assessment was part of the clinical workup, since two genetic syndromes—congenital Marfan’s syndrome2 and WeillMarchesani syndrome3—can present with identical ocular findings in infancy. The photograph in fact seems to suggest the possibility of a depressed nasal bridge, bilateral epicanthic folds, and doubtful hypertelorism. Even in the absence of any dysmorphic features, there is a possibility that this infant is affected with biallelic LTBP2 mutations, which have been reported to be causative in the ocular phenotype of megalocornea, microspherophakia, and lens dislocation.4 These children develop marfanoid habitus over time and need to be followed up. Additionally, owing to the autosomal recessive inheritance pattern, the risk of recurrence in subsequent pregnancies is 25%. This risk necessitates genetic counselling for the family, and, if mutation analysis is possible, the suitability of prenatal diagnosis can be discussed. I declare that I have no conflicts of interest.
Shagun Aggarwal [email protected]
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Ram J, Gupta N. Bilateral spontaneous anterior dislocation of crystalline lens in an infant. Lancet 2011; 378: 1501. Meire FM, Delleman WJ, Bleeker-Wagemakers EM. Ocular manifestations of congenital Marfan syndrome with contractures (CMC syndrome). Ophthalmic Paediatr Genet 1991; 12: 1–9. Dagoneau N, Benoist-Lasselin C, Huber C, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet 2004; 75: 801–06. Désir J, Sznajer Y, Depasse F, et al. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. Eur J Hum Genet 2010; 18: 761–67.
Authors’ reply We agree with Shagun Aggarwal that the child in our Clinical Picture also had a depressed nasal bridge, epicanthal folds, and hypertelorism in addition to bilateral megalocornea, spherophakia, and anterior dislocated crystalline lens. We did consider the possibility of connective tissue disorders such as Marfan’s syndrome and Weill-Marchesani syndrome, as well as isolated spherophakia. However, no abnormality was detected after a through systemic assessment by a paediatrician. Marfan’s syndrome is an autosomaldominant connective-tissue disorder involving the cardiovascular, skeletal, and ocular systems.1 Additionally, the skin, integument, lung muscle adipose, and dura can be affected.1 Weill-Marchesani syndrome is a rare systemic connective-tissue disease characterised by short stature, brachydactyly, ectopia lentis, and spherophakia.2 Desir and colleagues3 reported two families with megalocornea, nasal-inferonasal-superior lens dislocation, spherophakia, and high-arched palate and tall stature in all cases. Although our patient had bilateral megalocornea, spherophakia, and anterior dislocated crystalline lens, he did not have a high arched palate nor nasal-inferonasal-superior lens dislocation. The child underwent bilateral surgical lensectomy, anterior vitrect-
omy, and peripheral iridectomy, and had no postoperative complications at 6-month follow-up. The child had a right eye corneal diameter of 13·5 mm (horizontal) × 13·0 mm (vertical) and left eye corneal diameter of 14·5 mm × 14·0 mm, with no change in dimension after 6 months’ follow-up. Intraocular pressure was 12 mm Hg and 13 mm Hg in the right and left eye, respectively. Posterior segment examination showed a healthy optic disc and normal macula. The child can walk with the help of prescribed aphakic glasses. Paediatric assessment showed normal growth variables and no systemic abnormality. We agree with Aggarwal that, even in the absence of dysmorphic features, there is a possibility that this infant is affected with biallelic LTBP2 mutations, which are causative in the ocular phenotype of megalocornea, microspherophakia, and lens dislocation.3 Owing to financial constraints, the child and his parents did not undergo genetic analysis; however, the child is under regular and close follow-up for early detection of any ocular or systemic abnormalities. We declare that we have no conflicts of interest.
*Jagat Ram, Nishant Gupta [email protected] Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India 1
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Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev 2007; 17: 1–7. Jensen AD, Cross HE, Paton D. Ocular complications in the Weill-Marchesani syndrome. Am J Ophthalmol 1974; 77: 261–69. Désir J, Sznajer Y, Depasse F, et al. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. Eur J Hum Genet 2010; 18: 761–67.
www.thelancet.com Vol 379 April 14, 2012
1
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3
Forouzanfar MH, Foreman KJ, Delossantos AM, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet 2011; 378: 1461–84. Institute for Health Metrics and Evaluation. The challenge ahead: progress and setbacks in breast and cervical cancer. Seattle: IHME, 2011. http://www.healthmetricsandevaluation.org/ publications/policy-report/challenge-aheadprogress-and-setbacks-breast-and-cervicalcancer (accessed March 27, 2012). International Agency for Research on Cancer, World Health Organization. GLOBOCAN: data sources and methods. http://globocan.iarc.fr/ (accessed Sept 23, 2011).
Department of Genetics, Institute of Liver and Biliary Sciences, New Delhi, India 1
2
3
4
Bilateral anterior lens dislocation: the genetic perspective
Science Photo Library
Jagat Ram and colleagues (Oct 15, p 1501)1 describe an infant with bilateral spherophakia, megalocornea, and anterior lens dislocation, and report the systemic examination as being normal. I hope a genetic assessment was part of the clinical workup, since two genetic syndromes—congenital Marfan’s syndrome2 and WeillMarchesani syndrome3—can present with identical ocular findings in infancy. The photograph in fact seems to suggest the possibility of a depressed nasal bridge, bilateral epicanthic folds, and doubtful hypertelorism. Even in the absence of any dysmorphic features, there is a possibility that this infant is affected with biallelic LTBP2 mutations, which have been reported to be causative in the ocular phenotype of megalocornea, microspherophakia, and lens dislocation.4 These children develop marfanoid habitus over time and need to be followed up. Additionally, owing to the autosomal recessive inheritance pattern, the risk of recurrence in subsequent pregnancies is 25%. This risk necessitates genetic counselling for the family, and, if mutation analysis is possible, the suitability of prenatal diagnosis can be discussed. I declare that I have no conflicts of interest.
Shagun Aggarwal [email protected]
1392
Ram J, Gupta N. Bilateral spontaneous anterior dislocation of crystalline lens in an infant. Lancet 2011; 378: 1501. Meire FM, Delleman WJ, Bleeker-Wagemakers EM. Ocular manifestations of congenital Marfan syndrome with contractures (CMC syndrome). Ophthalmic Paediatr Genet 1991; 12: 1–9. Dagoneau N, Benoist-Lasselin C, Huber C, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet 2004; 75: 801–06. Désir J, Sznajer Y, Depasse F, et al. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. Eur J Hum Genet 2010; 18: 761–67.
Authors’ reply We agree with Shagun Aggarwal that the child in our Clinical Picture also had a depressed nasal bridge, epicanthal folds, and hypertelorism in addition to bilateral megalocornea, spherophakia, and anterior dislocated crystalline lens. We did consider the possibility of connective tissue disorders such as Marfan’s syndrome and Weill-Marchesani syndrome, as well as isolated spherophakia. However, no abnormality was detected after a through systemic assessment by a paediatrician. Marfan’s syndrome is an autosomaldominant connective-tissue disorder involving the cardiovascular, skeletal, and ocular systems.1 Additionally, the skin, integument, lung muscle adipose, and dura can be affected.1 Weill-Marchesani syndrome is a rare systemic connective-tissue disease characterised by short stature, brachydactyly, ectopia lentis, and spherophakia.2 Desir and colleagues3 reported two families with megalocornea, nasal-inferonasal-superior lens dislocation, spherophakia, and high-arched palate and tall stature in all cases. Although our patient had bilateral megalocornea, spherophakia, and anterior dislocated crystalline lens, he did not have a high arched palate nor nasal-inferonasal-superior lens dislocation. The child underwent bilateral surgical lensectomy, anterior vitrect-
omy, and peripheral iridectomy, and had no postoperative complications at 6-month follow-up. The child had a right eye corneal diameter of 13·5 mm (horizontal) × 13·0 mm (vertical) and left eye corneal diameter of 14·5 mm × 14·0 mm, with no change in dimension after 6 months’ follow-up. Intraocular pressure was 12 mm Hg and 13 mm Hg in the right and left eye, respectively. Posterior segment examination showed a healthy optic disc and normal macula. The child can walk with the help of prescribed aphakic glasses. Paediatric assessment showed normal growth variables and no systemic abnormality. We agree with Aggarwal that, even in the absence of dysmorphic features, there is a possibility that this infant is affected with biallelic LTBP2 mutations, which are causative in the ocular phenotype of megalocornea, microspherophakia, and lens dislocation.3 Owing to financial constraints, the child and his parents did not undergo genetic analysis; however, the child is under regular and close follow-up for early detection of any ocular or systemic abnormalities. We declare that we have no conflicts of interest.
*Jagat Ram, Nishant Gupta [email protected] Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India 1
2
3
Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev 2007; 17: 1–7. Jensen AD, Cross HE, Paton D. Ocular complications in the Weill-Marchesani syndrome. Am J Ophthalmol 1974; 77: 261–69. Désir J, Sznajer Y, Depasse F, et al. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. Eur J Hum Genet 2010; 18: 761–67.
www.thelancet.com Vol 379 April 14, 2012