Osteoporosis-pseudoglioma syndrome: Report of two cases and a manifesting carrier.
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.



Two probands (4 and 7 years of age respectively) and their parents were assessed by genetic analysis and comprehensive ophthalmic examination.



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.



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.
a MAGI Non-Profit Human Medical Genetics Institute , Rovereto ( TN ), Italy.
Paolo
P
Maltese
b Neuro-Ophthalmology Unit, "G.B. Bietti" Foundation - IRCCS , Rome , Italy.
Lucia
L
Ziccardi
c Department of Ophthalmology , Bambino Gesù IRCCS Children's Hospital , Rome , Italy.
Giancarlo
G
Iarossi
d Eye Clinic, Department of Neurosciences, Biomedicine and Movement , University and AOUI (Azienda Ospedaliera Universitaria Integrata) of Verona , Verona , Italy.
Elena
E
Gusson
e Medical Genetics Unit , IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy.
Leonardo
L
D'Agruma
d Eye Clinic, Department of Neurosciences, Biomedicine and Movement , University and AOUI (Azienda Ospedaliera Universitaria Integrata) of Verona , Verona , Italy.
Giorgio
G
Marchini
c Department of Ophthalmology , Bambino Gesù IRCCS Children's Hospital , Rome , Italy.
Luca
L
Buzzonetti
a MAGI Non-Profit Human Medical Genetics Institute , Rovereto ( TN ), Italy.|f Department of Medical and Surgical Sciences (DIMEC) , University of Bologna , Bologna , Italy.
Annalisa
A
Nicoletti
a MAGI Non-Profit Human Medical Genetics Institute , Rovereto ( TN ), Italy.
Sabrina
S
Benedetti
a MAGI Non-Profit Human Medical Genetics Institute , Rovereto ( TN ), Italy.
Matteo
M
Bertelli
D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density; D001842:Bone and Bones / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D004596:Electroretinography; D015785:Eye Diseases, Hereditary; D000080345:Familial Exudative Vitreoretinopathies; D005260:Female; D005451:Fluorescein Angiography; D006579:Heterozygote; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics*; D008297:Male; D010013:Osteogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000175:diagnosis / Q000235:genetics*
C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5
Familial exudative vitreoretinopathy; LRP5 gene; osteoporosis-pseudoglioma syndrome