|Year : 2020 | Volume
| Issue : 3 | Page : 334-335
Osteoporosis pseudoglioma syndrome
Vykuntaraju K Gowda1, Hemadri Vegda1, Sanjay K Shivappa2, Naveen Benakappa1
1 Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
2 Department of Pediatric Medicine, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
|Date of Submission||30-Apr-2020|
|Date of Decision||29-May-2020|
|Date of Acceptance||08-Jul-2020|
|Date of Web Publication||06-Nov-2020|
Prof. Vykuntaraju K Gowda
Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Osteoporosis pseudoglioma syndrome is characterized by intellectual disability, osteoporosis of bones and eye abnormalities. We report, a 14-year-old female child presented with walking difficulty with frequent falls followed by deformity of left leg. On examination, bilateral micropthalmia, microcornea, corneal clouding, vitreo-retinal detachment, and atrophic irises. She had deformity of left lower limb, anterior bowing of both tibia, lax skin, hyperextensible joints. Skeletal survey showed severe osteoporosis with fracture of left femur and fish mouth vertebra. She had normal serum calcium, phosphorus, and alkaline phosphatase levels. Targeted next generation testing revealed homozygous pathogenic variant in exon 6 at c.1096G>A/p.V366 M and confirmed by Sanger sequencing. Early diagnosis and treatment are helpful in preventing further fractures and osteoporosis.
Keywords: Intellectual disability, osteoporosis, pseudoglioma
|How to cite this article:|
Gowda VK, Vegda H, Shivappa SK, Benakappa N. Osteoporosis pseudoglioma syndrome. J Pediatr Neurosci 2020;15:334-5
Osteoporosis pseudoglioma (OPPG) syndrome is a rare autosomal recessive condition characterized by intellectual disability, osteoporosis of bones, and eye abnormalities. It is caused by mutation in gene LRP5 (LDL receptor-related protein) on chromosome 11q13.4. This protein helps in regulation of bone mineral density and development of retina. A 14-year-old female child, born of the nonconsanguineous marriage, presented with a history of walking difficulty with frequent falls since the last 3 years followed by deformity of the left leg. History of difficulty in vision and small eyes were noted from infancy. On examination, her head size was 46 cm (less than 3 SD), bilateral micropthalmia, microcornea, corneal clouding, vitreoretinal detachment, and atrophic irises [Figure 1]A. Such eye findings are called pseudoglioma of eye. She had deformity of left lower limb, anterior bowing of both tibia [Figure 1]B, lax skin, and hyperextensible joints. Radiological evaluation showed severe osteoporosis with fracture of left femur [Figure 1]C and [Figure 1]D and fish mouth vertebra [Figure 1]E and [Figure 1]F. She had normal serum calcium, phosphorus, and alkaline phosphatase levels. Targeted next-generation testing revealed homozygous pathogenic variant in exon 6 at c.1096G>A/p.V366M and confirmed by Sanger sequencing. Testing for parents showed heterozygous status for same pathogenic varmint in both parents.
|Figure 1: (A) Microphthalmia, microcornea, and corneal clouding. (B) Bowing of both lower limbs left more than right. (C) Fracture of shaft of left femur and severe thinning of bones. (D) Bowing of tibia with fracture of lower end of shaft of femur. (E and F) Generalized osteoporosis with fish mouth vertebra|
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We report a case of OPPG syndrome, with infantile onset of vision loss and severe osteoporosis. This child had micropthalmia, microcornea, corneal clouding, vitreoretinal detachment, and atrophic irises. Ocular findings may vary other than these. There are reports of band keratopathy, intraocular hemorrhage, and calcification. Few patients had preserved vision till teenage also. Most patients are blind before 25 years of age. Therefore, bone examination should be done whenever such eye findings are there and vice versa eye examination should be done with the severe bone abnormality. All patients manifest severe thinning of bones, bowing of extremities, and spinal deformities.
We considered the possibility of congenital rubella syndrome and excluded as the child does not have deafness and in the presence of severe osteoporosis of bones. We also considered the possibility of Osteogenesis imperfecta (OI); however, OI had ruled out as this child had no hearing loss, blue sclera, joint laxity, contractures, and teeth problems. In the presence of classical eye findings of pseudoglioma of eye with radiological features of severe osteoporosis we diagnosed as OPPG and confirmed by genetic testing. Osteoporosis and vertebral fractures are known to start in juvenile period. But few patients had earlier onset. Similar pathogenic mutation has been described by Tüysüz et al. Treatment options are regular bisphosphonates therapy which improves bone mineral density and prevents early fractures. Early diagnosis and treatment are helpful in preventing further fractures and osteoporosis.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
McDowell CL, Moore JD Multiple fractures in a child: the osteoporosis pseudoglioma syndrome. A case report. J Bone Joint Surg Am 1992;74:1247-9.
Ai M, Heeger S, Bartels CF, Schelling DK; Osteoporosis-Pseudoglioma Collaborative Group. Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet 2005;77:741-53.
Tüysüz B, Bursalı A, Alp Z, Suyugül N, Laine CM, Mäkitie O Osteoporosis-pseudoglioma syndrome: three novel mutations in the LRP5 gene and response to bisphosphonate treatment. Horm Res Paediatr 2012;77:115-20.