Alports syndrome is associated with RP and an abnormal glomerular-basement membrane leading to nephrotic syndrome. It is inherited as X-linked dominant. RP combined with ophthalmoplegia, dysphagia, ataxia, and cardiac conduction defects is seen in the mitochondrial DNA disorder Kearns–Sayre syndrome (also known as Ragged Red Fiber Myopathy)
RP combined with retardation, peripheral neuropathy, acanthotic (spiked) RBCs, ataxia, steatorrhea, and absence of VLDL is seen in abetalipoproteinemia. RP is seen clinically in association with several other rare genetic disorders (including muscular dystrophy and chronic granulomatous disease) as part of McLeod syndrome. This is an X-linked recessive phenotype characterized by a complete absence of XK cell surface proteins, and therefore markedly reduced expression of all Kell red blood cell antigens. For transfusion purposes, these patients are considered completely incompatible with all normal and K0/K0 donors. RP associated with hypogonadism, and developmental delay with an autosomal recessive inheritance pattern is seen with Bardet–Biedl syndromeOther conditions include neurosyphilis, toxoplasmosis and Refsums disease. Genetics
Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration.There are multiple genes that code for proteins needed in the visual pathway, when mutated, they can cause the retinitis pigmentosa phenotype. Inheritance patterns of RP have been identified as autosomal dominant, autosomal recessive, X-linked, and maternally (mitochondrially) acquired, and are dependent on the specific RP gene mutations present in the parental generation.
Taking account of its preferential uptake by bone and the alpha particles short range, radium-223 is estimated to give targeted osteogenic cells a radiation dose at least eight times higher than other non-targeted tissues. Clinical trials and FDA and EMA approval
The phase II study of radium-223 in castration-resistant prostate cancer (CRPC) patients with bone metastases showed minimum myelotoxicity and good tolerance for the treatment.223Ra successfully met the primary endpoint of overall survival in the phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer patients) study for bone metastases resulting from CRPC in 922 patients.The ALSYMPCA study was stopped early after a pre-planned efficacy interim analysis, following a recommendation from an Independent Data Monitoring Committee, on the basis of achieving a statistically significant improvement in overall survival (two-sided p-value = 0.0022, HR = 0.699, the median overall survival was 14.0 months for 223Ra and 11.2 months for placebo). Earlier phase II of the trial showed a median increased survival of 18.9 weeks (around 4.4 months). The lower figure of 2.8 months increased survival in interim phase III results is a probable result of stopping the trial; median survival time for patients still alive could not be calculated. A 2014 update indicates a median increased survival of 3.6 months.In May 2013, 223Ra received marketing approval from the U.S. Food and Drug Administration (FDA) as a treatment for CRPC with bone metastases in patients with symptomatic bone metastases and without known visceral disease.