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Andrea L Vincent, Gulunay Kiray, Sarah Hull; Harboyan Syndrome with biallelic SLC4A11 pathogenic variants misdiagnosed as congenital CMV infection. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1498.
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Harboyan syndrome is a rare autosomal recessive disorder characterised by congenital hereditary corneal endothelial dystrophy (CHED) with a later onset of sensorineural hearing loss (SNHL) due to pathogenic variants in the SLC4A11 gene. Congenital cytomegalovirus infection (CMV) may manifest with SNHL and visual impairment. We present a case of a 4 year old girl, diagnosed at birth with congenital CMV infection, but careful phenotyping and genetic testing permitted a definitive diagnosis.
Case report, clinical ocular and auditory phenotyping, next generation sequencing of corneal genes (Asper Ophthalmics), and parental segregation of variants
A 4 year old female presented with bilateral corneal clouding, and BCVA of 6/19 OD and 6/15 OS. At pregnancy her mother had a 2nd trimester febrile illness and converted from CMV negative to positive, with CMV detected in an umbilical blood sample. Age 2 months a faint corneal haze was noted and normal audiology at 2 months ( auditory brain response), and 8 months (otoacoustic emissions). At 18 months of age she developed a right esotropia, and was recorded as having clear corneas. A hypermetropic correction and patching was prescribed. Review at age 3.5 years showed bilateral moderate central corneal oedema, no evidence of bullae, central corneal thicknesses of 980 microns, and a clear periphery, with normal retina and optic nerves. Thought to be consistent with CHED, audiology was repeated demonstrating slight SNHL from 500-2000 Hz, sloping down to moderate SNHL at 8000Hz bilaterally. Genetic testing identified a previously reported pathogenic variant in SLC4A11 c.2609T>C, p.( Leu870Pro) and a second variant c.1318G>C, p.(Gly440Arg) with an allele frequency of 6.57e-6 in gnoMAD , and damaging by multiple in silico tools. Parental segregation of these variants was confirmed.
Congenital CMV infection affects 1% of all births although only 15-20% have sequelae. Although progressive SNHL may be a feature, corneal clouding is not described, with the most common ocular features being strabismus, optic atrophy, cortical visual impairment and chorioretinitis. Biallelic mutations in SLC4A11 are more commonly causative of isolated CHED2, but also described in the rarer Harboyan syndrome. The combination of cornal opacification and progressive SNHL should alert the clinicans to alternate diagnoses.
This is a 2021 ARVO Annual Meeting abstract.
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