Case#: LL89, F, Age of Diagnosis: 36 y.o., Ethnicity: Portuguese origin.
CasePresentingHPOs:HP:0000613 (Photophobia), HP:0000662 (Nyctalopia/Night blindness), HP:0030786 (Photopsia), HP:0001133 (Constriction of peripheral visual field), HP:0007663 (Reduced visual acuity), HP:0000551 (Color vision defect/loss of color vision), HP:0012508 (Metamorphopsia), HP:0000543 (Optic disc pallor/pale optic discs), HP:0000533 (Chorioretinal atrophy/generalized chorioretinal atrophy), HP:0002076 (Migraine)
CaseHPOFreeText: Proband was born a from consanguineous union between first degree cousins of Portuguese origin. She was diagnosed with a classical form of retinitis pigmentosa at the age of 36 years.
Initial visual complaints started with photophobia at 11 years of age and progressed to night blindness and photopsia by the age of 25. Constriction of the peripheral visual field was noted at the age of 28. Disease progression led to a sharp reduction in visual acuity at age 38 and to loss of color vision by the age of 40. The patient underwent cataract surgery at age 40 and 48. At 50 she developed metamorphopsia in the OS.
At the last ophthalmologic examination, patient P2 showed a BCVA of 0.3 in the OD, 0.16 in the OS, and severe constriction of the peripheral visual field, with bilateral tunnel-like vision, restricted to the 5 degrees central. Dilated fundus examination revealed attenuated retinal vessels, pale optic discs (Fig 2B) and a marked generalized chorioretinal atrophy in the posterior pole and in the periphery, with areas of complete atrophy in the inferior peripheral region of the right eye. Mild to moderate mottled pigment deposition in the retinal periphery, along with some irregular white patches in the posterior pole near the superior vessels, was also observed. Fundus autofluorescence was notable for generalized hypo-autofluorescence with a wide hyper-autofluorescent ring in the posterior pole (Fig 2D). SD-OCT revealed pronounced atrophy of the outer retinal layers and the presence of a foveal cyst (Fig 2F).
P2 gave birth to two children.
P2 displays a pale optic disc, vascular thinning and marked retinal changes, with opalescent areas of the retinal tissue in the periphery and central atrophic lesion. Scarse pigment deposition can also be found adjacent to the optic nerve head and periphery.
P2 suffered from frequent migraines and recently underwent a cerebral CT imaging examination, which revealed normal ventricular volumes and absence of other morphological anomalies.
CaseNotHPOs: N/A.
CaseNotHPOFreeText: N/A.
CasePreviousTesting: N/A.
CaseMethod1: N/A.
CaseMethod2: N/A.
CaseGenotypingMethod: WES and Sanger.
Variant: NM_012106.4:c.33_36del.
ClinVar: 2577503.
CAID: CA2580617535.
gnomAD: N/A.
VariantEvidence: N/A.
CaseAddInfo: Patient P2’s paternal aunt (P3) and her uncle (P4) were also diagnosed with RP, showing similar progression and manifestations. Specifically, P3 began to be visually impaired in her 20s with the onset of night blindness. Her visual field progressively shrank for both eyes and considerably worsened after the birth of her two daughters in her 30s, evolving to a state of complete blindness by the age of 50.
There is no clinical history of other ciliopathic disorders in this family, with the exception of P4, who suffered from chronic bronchitis. This latter patient died of multiple myeloma prior to this study, thus preventing further clinical analysis. Interestingly, P4 never conceived any offspring in spite of multiple attempts (as reported by his sister, patient P3), whereas both female patients P2 and P3 had two healthy children.
CasePMIDs: N/A.