Spherophakia, Isolated Clinical CharacteristicsOcular Features: Small, spherical lenses are characteristic of this entity. Lenticular myopia is usually present but no increased axial length. Glaucoma has been reported in several individuals and speculated to be due to pupillary block. No buphthalmos or angle anomalies were present. The lens may sublux into the vitreous cavity. Systemic Features: No skeletal, cardiovascular or metabolic disease is present. GeneticsIsolated spherophakia is an autosomal recessive disorder resulting from homozygous mutations in LTBP2 (13q24.1-q32.12). Parental consanguinity was present in reported families. Spherophakia is a clinically and genetically heterogeneous disorder and usually found in association with systemic findings. It is commonly seen in the Weill-Marchesani syndrome 1 (277600), in Weill Marchesani syndrome 2 (608328), in the Weill-Marchesani-Like syndrome (613195), in a condition known as ‘megalocornea, ectopia lentis, and spherophakia’ (?), another one called 'spherophakia and hernia' (157150), sulfite oxidase deficiency (272300), primary congenital glaucoma D (613086) and in a syndrome known as ‘spherophakia and metaphyseal dysplasia’ (157151). Pedigree: Autosomal recessiveTreatmentTreatment Options: The lenses may require extraction for secondary glaucoma and/or visual rehabilitation. ReferencesArticle Title: A homozygous mutation in LTBP2 causes isolated microspherophakia Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH. A homozygous mutation in LTBP2 causes isolated microspherophakia. Hum Genet. 2010 Oct;128(4):365-71. PubMed ID: 20617341 Clinical and genetic investigation of isolated microspherophakia in a consanguineous Tunisian family Ben Yahia S, Ouechtati F, Jelliti B, Nouira S, Chakroun S, Abdelhak S, Khairallah M. Clinical and genetic investigation of isolated microspherophakia in a consanguineous Tunisian family. J Hum Genet. 2009 Sep;54(9):550-3. PubMed ID: 19696795 Read more about Spherophakia, Isolated
A homozygous mutation in LTBP2 causes isolated microspherophakia Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH. A homozygous mutation in LTBP2 causes isolated microspherophakia. Hum Genet. 2010 Oct;128(4):365-71. PubMed ID: 20617341
Clinical and genetic investigation of isolated microspherophakia in a consanguineous Tunisian family Ben Yahia S, Ouechtati F, Jelliti B, Nouira S, Chakroun S, Abdelhak S, Khairallah M. Clinical and genetic investigation of isolated microspherophakia in a consanguineous Tunisian family. J Hum Genet. 2009 Sep;54(9):550-3. PubMed ID: 19696795
Megalocornea, Ectopia Lentis, and Spherophakia Clinical CharacteristicsOcular Features: Patients have megalocornea and mobile lenses. Corneal diameters are at least 13 mm in diameter. Some lenses are spherophakic (refractive errors may be in the +11-12 diopter range) and sometimes displace into the anterior chamber or cause pupillary block glaucoma. The clinical picture often resembles congenital glaucoma in young children but the elevated pressure is usually secondary to hypermobility of the lens and/or its spherical shape. Haab striae are not present but cloudy corneas have been reported in a few patients. Many patients develop phthisis or have severe reductions in vision. Systemic Features: Some but not all patients have several physical features of the Marfan syndrome (154700) such as high arched palate, tall stature, and narrow face but those tested do not have mutations in the FBN1 gene. GeneticsThis is an autosomal recessive disorder. Parental consanguinity is common. Homozygous mutations in the LTBP2 gene (14q24.3) are found in affected individuals. LTBP2 competes with LTBP1 (ADAMTSL2) for binding to the gene product of FBN1 in which mutations are associated with the Marfan syndrome (154700) and may account for the variable skeletal signs sometimes found in patients with this megalocornea syndrome. Both gene products are important to the structure of the extracellular matrix proteins of the ciliary processes, lens capsule, and lens epithelial layer. The different modes of inheritance and the unique mutations, of course, argue for separateness of the two disorders. Mutations in LTBP2 have also been found in a family with microspherophakia and ectopia lentis but corneal diameters were described as normal suggesting clinical heterogeneity. This is a unique disorder which previously has been classified as Glaucoma, Congenital Primary D (613086). The usual occurrence of ectopia lentis, the sometimes spherophakic nature of the lenses, the congenital presence of megalocornea without corneal edema in the absence of elevated intraocular pressure, and the lack of breaks in the Descemet membrane strongly suggest that this is not a primary congenital glaucoma. Pedigree: Autosomal recessiveTreatmentTreatment Options: Urgent lensectomy is necessary for lenses that migrate into the anterior chamber. Patients have to be monitored as lens dislocations can occur at any age. ReferencesArticle Title: Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations Khan AO, Aldahmesh MA, Alkuraya FS. Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations. Mol Vis. 2011;17:2570-9. PubMed ID: 22025892 LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea,spherophakia, and secondary glaucoma D?(c)sir J, Sznajer Y, Depasse F, Roulez F, Schrooyen M, Meire F, Abramowicz M. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea,spherophakia, and secondary glaucoma. Eur J Hum Genet. 2010 Jul;18(7):761-7. PubMed ID: 20179738 A homozygous mutation in LTBP2 causes isolated microspherophakia Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH. A homozygous mutation in LTBP2 causes isolated microspherophakia. Hum Genet. 2010 Oct;128(4):365-71. PubMed ID: 20617341 Null mutations in LTBP2 cause primary congenital glaucoma Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, Hejtmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy AL, Azmanov D, Tournev I, Cherninkova S, Jafri H, Raashid Y, Toomes C, Craig J, Mackey DA, Kalaydjieva L, Riazuddin S, Inglehearn CF. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009 May;84(5):664-71. PubMed ID: 19361779 Read more about Megalocornea, Ectopia Lentis, and Spherophakia
Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations Khan AO, Aldahmesh MA, Alkuraya FS. Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma - a distinct phenotype caused by recessive LTBP2 mutations. Mol Vis. 2011;17:2570-9. PubMed ID: 22025892
LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea,spherophakia, and secondary glaucoma D?(c)sir J, Sznajer Y, Depasse F, Roulez F, Schrooyen M, Meire F, Abramowicz M. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea,spherophakia, and secondary glaucoma. Eur J Hum Genet. 2010 Jul;18(7):761-7. PubMed ID: 20179738
A homozygous mutation in LTBP2 causes isolated microspherophakia Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH. A homozygous mutation in LTBP2 causes isolated microspherophakia. Hum Genet. 2010 Oct;128(4):365-71. PubMed ID: 20617341
Null mutations in LTBP2 cause primary congenital glaucoma Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, Hejtmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy AL, Azmanov D, Tournev I, Cherninkova S, Jafri H, Raashid Y, Toomes C, Craig J, Mackey DA, Kalaydjieva L, Riazuddin S, Inglehearn CF. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009 May;84(5):664-71. PubMed ID: 19361779
Glaucoma, Congenital Primary D Clinical CharacteristicsOcular Features: Evidence of glaucoma can appear in early childhood but may appear much later. However, typical signs such as enlarged corneas or frank buphthalmos, cloudiness of the corneas, tearing and photophobia are present only when the pressure is elevated due to pupillary block or when the lens migrates into the anterior chamber. Most patients have additional signs such as ectopia lentis and spherophakia. Systemic Features: Some patients have osteopenia, a high arched palate, and a marfanoid habitus. GeneticsThis form of congenital glaucoma has been described primarily in Middle Eastern and Asian as well as Roma/Gypsy families and is inherited in an autosomal recessive pattern. The mutations occur in the LTBP2 gene (14q24) which is in close proximity to GLC3C, another putative gene with mutations causing congenital glaucoma. Mutations in other genes are also associated with primary congenital glaucoma such as in CYP1B1 causing type A (231300) and in GLC3B causing type B (600975). THIS IS NOT A PRIMARY GLAUCOMA DISORDER. Microspherophakia and ectopia lentis are not features of primary congenital glaucoma. Elevated pressures in these patients are found only when there is a pupillary block or when the lens dislocates into the anterior chamber. The enlarged cornea is clear and has no breaks in the Descemet membrane. THIS CONDITION IS THEREFORE RECLASSIFIED AS "MEGALOCORNEA, ECTOPIA LENTIS, AND SPHEROPHAKIA". Pedigree: Autosomal recessiveTreatmentTreatment Options: The usual surgical and pharmacological treatments for glaucoma apply but vision preservation is a challenge. The spherophakic or dislocated lenses may need to be removed. ReferencesArticle Title: LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population Azmanov DN, Dimitrova S, Florez L, Cherninkova S, Draganov D, Morar B, Saat R, Juan M, Arostegui JI, Ganguly S, Soodyall H, Chakrabarti S, Padh H, L??pez-Nevot MA, Chernodrinska V, Anguelov B, Majumder P, Angelova L, Kaneva R, Mackey DA, Tournev I, Kalaydjieva L. LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population. Eur J Hum Genet. 2011 Mar;19(3):326-33. PubMed ID: 21081970 Null mutations in LTBP2 cause primary congenital glaucoma Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, Hejtmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy AL, Azmanov D, Tournev I, Cherninkova S, Jafri H, Raashid Y, Toomes C, Craig J, Mackey DA, Kalaydjieva L, Riazuddin S, Inglehearn CF. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009 May;84(5):664-71. PubMed ID: 19361779 Read more about Glaucoma, Congenital Primary D
LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population Azmanov DN, Dimitrova S, Florez L, Cherninkova S, Draganov D, Morar B, Saat R, Juan M, Arostegui JI, Ganguly S, Soodyall H, Chakrabarti S, Padh H, L??pez-Nevot MA, Chernodrinska V, Anguelov B, Majumder P, Angelova L, Kaneva R, Mackey DA, Tournev I, Kalaydjieva L. LTBP2 and CYP1B1 mutations and associated ocular phenotypes in the Roma/Gypsy founder population. Eur J Hum Genet. 2011 Mar;19(3):326-33. PubMed ID: 21081970
Null mutations in LTBP2 cause primary congenital glaucoma Ali M, McKibbin M, Booth A, Parry DA, Jain P, Riazuddin SA, Hejtmancik JF, Khan SN, Firasat S, Shires M, Gilmour DF, Towns K, Murphy AL, Azmanov D, Tournev I, Cherninkova S, Jafri H, Raashid Y, Toomes C, Craig J, Mackey DA, Kalaydjieva L, Riazuddin S, Inglehearn CF. Null mutations in LTBP2 cause primary congenital glaucoma. Am J Hum Genet. 2009 May;84(5):664-71. PubMed ID: 19361779
