Abstract
Purpose :
Primary concomitant strabismus (PCS) comprising intermittent exotropia (IE) and accommodative esotropia (ET) are two common forms of ocular misalignment. Familial forms of PCS have been observed across all populations. However, no definitive mode of inheritance or any genetic determinants have been concretely established for the same. Recently next generation sequencing technology has emerged as a powerful tool in discovery genomics and a large number of novel disease-causing variants are being reported. As a first step, we recruited informative families with PCS for subsequent genetic analysis for disease-causing variant identification.
Methods :
All consecutive families of north Indian origin, with two or more affected members with PCS were recruited at the ophthalmic outpatient’s department of Lady Hardinge Medical College and Dr RML Hospital, New Delhi, India from August 2014 to November 2019. Detailed phenotypic evaluation of the proband and other affected family members was performed. Pedigree documentation was done by Cyrillic 3.0.400 software.
Results :
Of the 70 recruited PCS families so far, 100% concordance of phenotype was observed in 63 (90%), 23 with ET and 40 with XT. In 5 families, the affected members demonstrated both, ET and XT. However, in 3 of these, the different phenotypes were of relatives bonded by marriage and hence have lesser significance as being demonstrative of discordance. In 2 families, one of the siblings each had XT and the other sibling demonstrated Duane’s retraction syndrome (DRS). 16/23 ET (69.5%), 33/40 XT (82.5%) and 1 of 2 (50%) families demonstrating both ET and XT in members related by blood, had PCS in at least two generations, implying vertical transmission. Maternal transmission was observed in 12/16 (75%) ET and 22/33 (67%) XT families with vertical transmission, the rest demonstrated transmission from the paternal side. Consanguinity was observed in 2 families, both with ET. In two families with XT and likely autosomal recessive inheritance, nystagmus and low vision were additional phenotypes. In another two families with XT, the proband had autism in one and an associated mitochondrial myopathy in the other.
Conclusions :
Pedigree analysis of this large and unique familial cohort with PCS in the geographical location of north India, recruited for future genetic analysis, opens up perspectives on the phenotypic heterogeneity of the condition in this population.
This is a 2020 ARVO Annual Meeting abstract.