Coffin-Siris syndrome (CSS) is a rare heterogenous genetic disorder first described in 1970. The diagnosis is considered in children with cognitive/developmental delay, 5th finger hypoplasia and characteristic facial features. There is, however, significant variability in the phenotypic appearance, making clinical diagnosis challenging [1, 2].

Fig. 1
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a Ahmed Valve in situ, b Severe VKC, c Foster-Fuchs spot

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Fig. 2
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Glaucomatous optic disc cupping

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Numerous ocular features associated with the syndrome have been reported in the literature: strabismus, nystagmus, cataract, hypophoria, astigmatism, hypermetropia and anisomyopia [3].

We present two cases of children in Northern Ireland with a confirmed genetic diagnosis of CSS (mutation in the ARID1B gene), both having developed significant issues with raised intra-ocular pressure (IOP). We believe glaucoma to be a novel feature of this syndrome.

Our first case exhibited global developmental delay and learning difficulties, hypertonia, small ASD, short stature, hearing loss and speech dyspraxia. The child was found to have a mutation in the ARID1B gene and diagnosed with CSS at 9 years of age. From an ophthalmic perspective, significant anisomyopia was a feature, with the left eye (LE) being more myopic than the right eye (RE), along with a right divergent squint and amblyopia. Severe vernal kerato-conjunctivitis (VKC) presented at age 7 with the development of recurrent shield ulcers. Interestingly, this is not a known association of CSS. In addition to anti-histamines and topical Cyclosporin, he was treated with topical and subtarsal steroids for many years. At age 8, he suddenly developed IOPs of 40 mmHg in both eyes associated with optic disc cupping (0.4 cup:disc RE and 0.6 cup:disc LE). Despite maximal topical therapy and discontinuing steroids, the child’s IOPs remained elevated. Filtration surgery with Ahmed valve insertion was ultimately required on both eyes. VKC was controlled with Omalizumab and all steroids were avoided. Thereafter, IOPs remained stable for 4 years. During this time, he also developed a right Foster–Fuchs choroidal neovascular membrane requiring intravitreal Lucentis therapy. Unfortunately, 5 months ago his pressures suddenly spiked again to a high (30 s) in both eyes, despite having not been on steroids for many years. The role of steroids in the development of his juvenile onset glaucoma remains unclear (Fig. 1).

Our second case was referred to ophthalmology at age 13 weeks following an antenatal finding of Corpus Callosum agenesis. After genetic testing she was diagnosed with CSS, possessing the same mutation as our first case. The patient exhibited developmental delay and delayed visual maturation, with progressive anisomyopia being the most significant ocular feature associated with right divergent squint and amblyopia. From 4 months, rising IOPs were noted in both eyes, associated with disc cupping. Interestingly, the least myopic eye developed the more advanced glaucomatous disc cupping. Currently her pressures are managed with topical therapy (Fig. 2).

Both our cases display already reported ocular features of CSS—progressive anisomyopia and unilateral divergent squint with associated amblyopia. However, the development of glaucomatous features common to both cases is interesting and not previously reported in the literature. The exact mechanism of this open-angle glaucoma is unclear, and further investigation into the structural ocular abnormalities present in CSS is necessary to evaluate whether this genotype (ARID1B mutation) is linked to the development of glaucoma.

Disclaimer

The authors declare that the material presented is original research, has not been previously published and has not been submitted for publication elsewhere while under consideration.