Keratoconus in a patient with B3GALT6‐related disorder

Abstract

To the Editor: B3GALT6 is a single exon gene on 1p36.33, and it encodes β3GalT6 (β-1,3galactosyltransferase 6), which functions in glycosaminoglycans (GAG) synthesis. Biallelic mutations in B3GALT6 lead to reduced GAG synthesis, activity, and abnormal collagen structure. To date, approximately 60 patients from 40 families have been molecularly identified and reported with spondylodysplastic EDS due to B3GALT6deficiency (spEDS-B3GALT6). The condition exhibits a pleiotropic phenotype, allelic heterogeneity, and wide clinical variability. Brady described the hallmarks of the disorder. Ocular findings described so far in spEDS-B3GALT6 include refractive errors, corneal clouding, microcornea, glaucoma, blue sclerae, proptotic eyes, small optic nerves, and retinal abnormalities including detachment. Keratoconus has not been previously described in these patients. The proband was referred to our clinic for poor wound healing following surgery for keratoconus at age 38 years. His medical history was additionally pertinent for short stature. Birth growth parameters are unavailable. Per available history short stature was not a concern until age 1–2 years. Between ages 3 and 5 years, he started experiencing low back pain, and he was later diagnosed with spinal stenosis. In his early teenage years (13–14 years), increased mobility of his knees and ankles was noted. He began noticing a deterioration of his vision. A lumbar laminectomy was performed at age 22 years to treat symptoms of central spinal stenosis. At age 29 years, he was diagnosed with keratoconus, characterized by progressive, bilateral, corneal steepening and thinning (Figure 1a). At age 37 years, the patient underwent Bowman layer transplantation in one eye in an attempt to arrest the progression of his keratoconus. While the operation was technically successful, corneal steepening and thinning continued until a second procedure, corneal crosslinking (CXL) was performed which, so far, has resulted in corneal stability. The proband has no history of learning disabilities. His parents are unaffected. He and his younger sister share similar features. His sister has two unaffected children. Additionally, there are no other family members with eye problems similar to our patient. Physical examination at age 38 years was notable for height of 141.40 cm (−4.6 SD) and weight of 109 kg (BMI 54.52). He has macrocephaly, flat face, prominent forehead, prominent eyes, depressed and wide nasal bridge, long upper lip, low set ears, high arched palate, broad fingers and toes, increased creases in the skin of the palms, bowed legs, flat feet, and increased finger laxity (Figure 1b). His skin is soft, with a doughy texture mostly in the hands.