TY - JOUR
T1 - Osteoporosis-pseudoglioma syndrome
T2 - Report of two cases and a manifesting carrier
AU - Maltese, Paolo
AU - Ziccardi, Lucia
AU - Iarossi, Giancarlo
AU - Gusson, Elena
AU - D’Agruma, Leonardo
AU - Marchini, Giorgio
AU - Buzzonetti, Luca
AU - Nicoletti, Annalisa
AU - Benedetti, Sabrina
AU - Bertelli, Matteo
PY - 2017/9/3
Y1 - 2017/9/3
N2 - Background: Osteoporosis-pseudoglioma syndrome is a very rare disease mainly characterized by severe eye abnormalities and osteoporosis but also causing a broader range of clinical features. The syndrome is associated with homozygous or compound heterozygous variations in the LRP5 gene. In this report, we describe two children with a severe early-onset form of familial exudative vitreoretinopathy associated with skeletal abnormalities. Materials and methods: Two probands (4 and 7 years of age respectively) and their parents were assessed by genetic analysis and comprehensive ophthalmic examination. Results: In both probands, the diagnosis of osteoporosis-pseudoglioma syndrome was confirmed by detection of three new pathogenic LRP5 variants: p.(Asp379Asn), found in the homozygous state in one proband, and p.(Asp203Ala) in the compound heterozygous state with p.(Cys612Valfs*25) in the other. The clinical and genetic study was extended to their parents, confirming that heterozygous carriers may also have incomplete clinical manifestation of this syndrome. Conclusions: To our knowledge, these are the first two cases of the syndrome described in Italy. Genetic testing proved to be fundamental for definition of the syndrome and confirms the importance of early detection of LRP5 variants for management of systemic features of the disease in patients and carrier relatives.
AB - Background: Osteoporosis-pseudoglioma syndrome is a very rare disease mainly characterized by severe eye abnormalities and osteoporosis but also causing a broader range of clinical features. The syndrome is associated with homozygous or compound heterozygous variations in the LRP5 gene. In this report, we describe two children with a severe early-onset form of familial exudative vitreoretinopathy associated with skeletal abnormalities. Materials and methods: Two probands (4 and 7 years of age respectively) and their parents were assessed by genetic analysis and comprehensive ophthalmic examination. Results: In both probands, the diagnosis of osteoporosis-pseudoglioma syndrome was confirmed by detection of three new pathogenic LRP5 variants: p.(Asp379Asn), found in the homozygous state in one proband, and p.(Asp203Ala) in the compound heterozygous state with p.(Cys612Valfs*25) in the other. The clinical and genetic study was extended to their parents, confirming that heterozygous carriers may also have incomplete clinical manifestation of this syndrome. Conclusions: To our knowledge, these are the first two cases of the syndrome described in Italy. Genetic testing proved to be fundamental for definition of the syndrome and confirms the importance of early detection of LRP5 variants for management of systemic features of the disease in patients and carrier relatives.
KW - Familial exudative vitreoretinopathy
KW - LRP5 gene
KW - osteoporosis-pseudoglioma syndrome
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U2 - 10.1080/13816810.2016.1253107
DO - 10.1080/13816810.2016.1253107
M3 - Article
C2 - 28145787
AN - SCOPUS:85011288777
VL - 38
SP - 473
EP - 479
JO - Ophthalmic Genetics
JF - Ophthalmic Genetics
SN - 0167-6784
IS - 5
ER -