Clinical spectrum of choroideremia in pediatric carriers of CHM gene mutations

Background. Choroideremia (CHM, OMIM 303100) is a rare (1 in 50,000 males) hereditary bilateral retinal dystrophy with an X-linked recessive inheritance pattern. The disease leads to progressive vision loss due to the primary degeneration of the choriocapillaris, followed by progressive atrophy of the retinal pigment epithelium (RPE) and photoreceptors. Female carriers of pathogenic variants in the CHM gene may also manifest clinical symptoms. Purpose: to present the phenotypic characteristics of choroideremia in pediatric carriers of a CHM gene mutation. Materials and methods. This article describes a clinical case of choroideremia associated with a CHM gene mutation in two sisters aged 4 and 2 years. The parents consulted an ophthalmologist due to complaints of reduced distance vision in the elder daughter. In addition to standard ophthalmologic examination, both patients underwent spectral-domain optical coherence tomography (SD-OCT) and electrophysiological testing (ERG). Molecular genetic testing was conducted for diagnostic confirmation and detection of the pathogenic nucleotide variant, preceded by collection of family history. Results. A detailed pedigree analysis and comprehensive examination of biological relatives across three generations confirmed an X-linked mode of inheritance of the disease. Best-corrected visual acuity (BCVA) in both girls was 0.9. The high visual acuity correlated with the preserved foveal architecture observed on spectral-domain optical coherence tomography (SD-OCT), which demonstrated an intact trilaminar structure comprising Bruch’s membrane, the retinal pigment epithelium (RPE), and the external limiting membrane. The ellipsoid zone (EZ), corresponding to the junction between the inner and outer segments of photoreceptors, was absent in the peripheral retina but remained preserved within the foveal region. Electrophysiological evaluation was limited due to the young age of the patients. Molecular genetic testing of family members revealed a previously unreported pathogenic variant in exon 10 of the CHM gene, resulting in a premature stop codon at position 445 (p.Ser445*) in a hemizygous state. This variant is consistent with the molecular characteristics of choroideremia, a form of inherited retinal degeneration (IRD). Conclusion. An etiopathogenetic diagnostic approach and molecular genetic testing enabled the accurate identification of the specific IRD subtype–choroideremia. Pediatric carriers of the pathogenic variant in exon 10 of the CHM gene may exhibit early signs of chorioretinal degeneration, detectable by OCT and ERG.