Author: Marta Isabel Martínez Sánchez (Spain)
Co-authors: Beatriz Gonzalo Suárez, Carlos Vera Lara
To describe characteristic clinical-ophthalmological findings of bilateral macular pseudocoloboma in a patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis disease (FHHNC) and establish a differential diagnosis with macular diseases with similar fundoscopic appearances.
Retina Subspecialty, Hospital Universitario ‘‘Príncipe de Asturias’’ at Alcalá de Henares, Madrid.
The following is a case of bilateral macular pseudocoloboma in a 16-year-old child with past history of FHHNC caused by a mutation in the gene CLDN19 diagnosed at age of 3 years old. The child was referred to our hospital for ophthalmologic evaluation. Best corrected visual acuity (BCVA) was of 20/63 in both eyes (OU). Anterior segment showed a mild congenital Y-suture cataract. Intraocular pressure measurements were in range and both pupils were equal, reactive to light with no relative afferent pupillary defect. A 15-degrees exotropia with left eye ocular dominance was observed. Ophthalmologic history includes mild myopia. Fundus examination revealed lesions occupying the macular region OU that simulates areas of scarring combined with retinal atrophy plaques. The scars were similar to those caused by toxoplasma retinochoroiditis while in atrophy plaques, only the bare sclera appeared with the absence of choroidal vessels and retinal structures. The optic nerve and retinal periphery showed no interesting findings. Autofluorescence images OU showed a central hypoautofluorescent lesion corresponding to retinal pigmented epithelium (RPE) and photoreceptor atrophy. Optical coherence tomography (OCT) demonstrated a cup-shaped macular lesion with a severe neurosensory retina and RPE atrophy together with a decrease in choroidal thickness.
Given the atrophy of the outer retina/RPE/choroid together with a mutation in the gene CLDN19 the existence of macular pseudocoloboma due to FHHNC disease was confirmed. Electroretinography showed normal scotopic function and mildly abnormal photopic function.
FHHNC is a rare tubulopathy with recessive inheritance characterized by hypomagnesemia, hypercalciuria, nephrocalcinosis, renal insufficiency and ocular abnormalities. It is caused by a mutation in CLDN16 and CLDN19 genes which encode a protein expressed both in the Henle’s loop and in the RPE. CLDN19 expression in RPE is higher than that of gene CLDN16 causing severe ocular involvement(strabismus, macular pseudocoloboma, nystagmus or myopia). A differential diagnosis of macular pseudocoloboma based on fundoscopic features must be established. Ocular toxoplasmosis may present with similar appearance, visualizing active lesions seen as whitish foci of retinochoroiditis adjacent to pigmented atrophic scars with vitritis and uveitis often associated. Similar fundoscopy can also be observed in North Carolina macular dystrophy (NCMD), an inherited disorder caused by chromosome 5 and 6 mutations. NCMD grade 3, defined by the affection of choriocapillaris and RPE (colobomatous or stafilomatous lesions), could be similar to pseudocoloboma. In this cases, genetic testing and clinical findings can lead to diagnosis. As reported, SD-OCT along with autofluorescence confirmed the complete absence neurosensory retina, choriocapillaris and RPE. These findings together with the presence of renal dysfunction and the genetic study lead us to the diagnosis of macular pseudocoloboma in the context of a FHHNC disease.
Financial disclosures of all authors. Funding: None.