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Diving Deeper Into the Blue: a Case of Osteogenesis Imperfecta with Ocular Involvement Undiagnosed for 25 Years

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Diving Deeper Into the Blue: a Case of Osteogenesis Imperfecta with Ocular Involvement Undiagnosed for 25 Years Title: Diving deeper into the blue: a case of osteogenesis imperfecta with ocular involvement undiagnosed for 25 years Author(s): Janki H Parikh, OD, Mariya Skreydel OD, MS, Rochelle Mozlin, OD, MPH, FCOVD, FAAO Abstract: A detailed look into a 25-year old female’s seemingly benign history and ocular exam aids in diagnosing and properly managing her long-undetected osteogenesis imperfecta. I. Case History • Patient demographics: 25-year-old Indian female • Chief complaint: Patient presents with floaters OU and concern about blueish tint in sclera OU • Ocular, medical history: o Myopia OU: Patient wears SV glasses and Proclear Daily contact lenses. o Endoscopic Skull Base Encephalocele Surgery (June 2013): Patient reports she had a continuous cerebrospinal fluid (CSF) leak out of her left nostril for 20 years. She was misdiagnosed with allergic rhinitis by several providers and treated with anti-histamines and steroid nasal sprays for years. CSF leak resolved with surgery after CT and MRI scans revealed herniation of frontal lobe tissue into the left nasal cavity from a skull base fracture at 18 months of age. o Headaches: frequent severe throbbing frontal headaches, resolved after surgery • Medications: None • Other salient information: Patient reports father has similar blueish tint in his eyes. He became deaf at the age of 35; unknown etiology at this time. Patient is being followed by an ENT yearly; hearing in left ear is slightly below average. Patient reports weakness, easy bruising, and several fractures in past (skull base, both arms, leg, floating ribs, toe fractures, and finger dislocation) from very minor trauma. II. Pertinent findings • Clinical: Distance and near BCVA 20/20 with -3.00sph Rx OU, blue sclera OU on slit lamp and external observation, CCT 495/499, IOPs 18/18, C/D 0.6R/0.6R, posterior vitreous detachment OU • Physical: Increased joint laxity and overall flexibility • Laboratory studies (ordered by referral to PCP): Bloodwork, (+) Vitamin D insufficiency • Radiology studies (ordered by referral to endocrinologist): DEXA Bone Density Scan, (+) Osteopenia • Others (ordered by referral to endocrinologist): Genetic Testing, (+) COL1A1 gene mutation III. Differential diagnosis • Primary/leading: Type 1 Osteogenesis Imperfecta (OI) • Others: Other conditions affecting bones and collagen production such as: Bruck syndrome, Hypophosphatasia, Idiopathic juvenile osteoporosis, and Child abuse/neglect. IV. Diagnosis and discussion • Elaborate on the condition: o Osteogenesis Imperfecta (OI) is a genetic disorder characterized mainly by defects in Type 1 collagen synthesis. Type 1 collagen is a major structural protein found in bones, skin, ligaments, connective tissues, and the eye. It is caused by a mutation in one of two genes (COL1A1 and COL1A2), that encode the alpha chains of collagen type 1. There are multiple subtypes of OI which exhibit several phenotypic differences varying from very mild to lethal. Most moderate to severe types of OI typically have a point mutation affecting a glycine residue in these genes producing a mixture of normal and abnormal collagen. Type 1 OI, the mildest and most common autosomal dominant form with a normal life span, usually has mutations with a premature stop codon within the gene. These products are very unstable and destroyed, leaving only normal collagen chains in a reduced amount. Incidence is approximately 1 in 20,000 live births. Although the prevalence is similar worldwide with about 25,000 to 50,000 cases, this figure may actually be higher given the often underdiagnosed nature of the condition. • Expound on unique features: o Patients with OI tend to have bones that fracture easily and are predisposed to dislocations, loose joints and muscle weakness, skin that bruises easily, blue, purple, or gray tinted sclera, tendency toward spinal curvature, and possible hearing loss beginning in early 20s-30s. V. Treatment, management • Treatment and response to treatment: o Patient was referred to a PCP and Bone Disease endocrinologist for bloodwork, DEXA scan to assess bone quality, and genetic testing if necessary. After receiving results and a definitive diagnosis of OI, patient was prescribed 1000mg Vitamin D and Calcium supplements daily, low impact strengthening exercises, and low estrogen birth control pills to prevent bone density loss. o The goal of treatment is to reduce fracture rates, prevent long-bone deformities and scoliosis, control symptoms such as hearing loss, dental issues, and osteoporosis, and improve functional outcome. Current medical treatments including hormones, steroids, and high dose vitamins and minerals have shown little clinical effectiveness. IV Bisphosphonates used for osteoporosis can be used for moderate to severe forms of OI but is associated with atypical fractures after long- term use in adults. o Proper management include referrals to Physical Therapy, Orthopedics, Endocrinology, Genetic Counseling, Audiology, and Nutritionist as needed. o Early stages of preclinical research in transplanting Bone Marrow-Derived Mesenchymal Cells differentiated into osteoblasts or using Mesenchymal stem cells (MSCs) to inactivate mutant COL1A1 and COL1A2 demonstrates some therapeutic future potential. • Bibliography, literature review encouraged o Golshani K, Ludwig M, Cohn P, Kruse R. Osteogenesis Imperfecta. Del Med J 2016;88(6):178-85. o Horwitz EM, Prockop DJ, Fitzpatrick LA, et al. Transplantability and Therapeutic Effects of Bone Marrow-Derived Mesenchymal Cells in Children with Osteogenesis Imperfecta." Nature Medicine 1999: 309-13. o Chamberlain J, Deyle D, Russell D, et al. Gene Targeting of Mutant COL1A2 Alleles in Mesenchymal Stem Cells from Individuals with Osteogenesis Imperfecta. Molecular Therapy 2008;16:187-93. VI. Conclusion • Clinical pearls, take away points if indicated o Type 1 OI is often undiagnosed due to its normal phenotypic appearance and mild severity of symptoms. Optometrists may play a primary role in detection with a thorough case history and examination. It is important to ask follow up questions regarding fracture history in patients with blue sclera and make appropriate referrals for imaging, testing, and management. o Since collagen is an integral protein in the eye, OI can affect the cornea, trabecular meshwork, the lens, sclera, optic nerve, lamina cribrosa, and the eyelids. Associated ocular diseases include POAG, retinal detachment, and keratoconus. For this reason, annual eye examinations are essential. Always prescribe protective eyewear and refrain from referral for refractive surgery due to risk of ectasia from thin corneas. .
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