Oman Journal of Ophthalmology

: 2022  |  Volume : 15  |  Issue : 3  |  Page : 385--388

An association between bilateral keratoconus in a patient with spondyloocular syndrome and xylosyltransferase II gene mutation

Sara Fathi-Nieto, Rodrigo Butrón-Ruiz, Enrique García-Soler, Ana Hervás-Ontiveros, Amparo Ortiz-Seller 
 Department of Ophthalmology, University and Polytechnic La Fe Hospital, Valencia, Spain

Correspondence Address:
Sara Fathi-Nieto
C/Avenida Fernando Abril Martorell, 106, ES-46026 Valencia


Spondyloocular syndrome (SOS) is a rare autosomal-recessive disorder. Since 2015, SOS has been linked to mutations in xylosyltransferase II (XYLT2) locus. Phenotypic features could affect multiple systems, such as sight, hearing, or bones. Herein, we report a case of SOS with multiple bone fractures without trauma, bilateral cataracts, and sensorineural hearing loss. Mutations in XYLT2 gene were detected, and the diagnosis of SOS was made. At the age of 8, the patient presented with progressive vision loss. Slit-lamp examination revealed inferior steepening, apical scarring, and thinning of the cornea. Due to keratoconus suspicion, a corneal tomography was done, confirming the diagnosis of keratoconus. We present the first case of bilateral keratoconus in a patient with SOS.

How to cite this article:
Fathi-Nieto S, Butrón-Ruiz R, García-Soler E, Hervás-Ontiveros A, Ortiz-Seller A. An association between bilateral keratoconus in a patient with spondyloocular syndrome and xylosyltransferase II gene mutation.Oman J Ophthalmol 2022;15:385-388

How to cite this URL:
Fathi-Nieto S, Butrón-Ruiz R, García-Soler E, Hervás-Ontiveros A, Ortiz-Seller A. An association between bilateral keratoconus in a patient with spondyloocular syndrome and xylosyltransferase II gene mutation. Oman J Ophthalmol [serial online] 2022 [cited 2023 Feb 7 ];15:385-388
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Full Text


Spondyloocular syndrome (SOS) is a rare disease, first suspected in 2001, in a family with consanguineous healthy parents and children affected with the same clinical features.[1] These features included bilateral cataracts, retinal detachment, osteoporosis, and platyspondyly, but any mutation was found.[1],[2] In 2006, two siblings with cataracts, sensorineural hearing loss, osteoporosis, and mild learning defects underwent genetic testing. The whole-exome sequencing on the genomic DNA revealed a homozygous frame-shift duplication in exon 3 of xylosyltransferase II (XYLT2) (NM_022167.3:c. 692dup) that results in a decreased circulating XylT activity and fibroblasts. Their parents were also heterozygous for this mutation.[3]

Since 2006 to date, 17 patients with mutations in XYLT2 gene and SOS have been reported.[4] The origins of these families were Turkish, Pakistani, and European Australian. Besides, clinical features such as flat cornea, heart defects, ureter dilatation, dental anomaly, facial dysmorphism, long bones fracture, and flat feet were also described.[1],[2],[3],[4],[5],[6],[7]

 Case Report

A 1-year-old female child from consanguineous healthy parents from Morocco was evaluated in our hospital after having fracture of the right acromion, right femur, and right parietal bones. She also presented pectus carinatum, platyspondyly, as well as multiple vertebral fractures. Furthermore, the patient was diagnosed of bilateral cataract and underwent uneventful bilateral cataract surgery. Blood test, abdominal ultrasound, and brain MRI were performed with normal results, but brainstem evoked response audiometry study showed a mild-to-moderate bilateral sensorineural hearing loss. The study for metabolic diseases was also negative.

Molecular testing was performed when she was 1 year old, on suspicion of imperfecta osteogenesis (COL1A1 and COL1A2 genes) being negative. Treatment with intravenous pamidronate was started, and since then, she had received 18 doses. In 2016, the genetic examination was expanded by next-generation sequencing (NSG), identifying homozygosity for a deletion in exon 8 of XYLT2 gene (NM_022167.3:c. 1512_1519del). Her parents were also genetically studied by NSG, and the test confirmed that they were heterozygous for the same mutation. Due to the clinical features (cataracts, fragile bones, multiple bone fractures, platyspondyly, and sensorineural hearing loss) and the homozygous XYLT2 mutation, the diagnosis of SOS was made.

The patient was lost to follow-up in the ophthalmology department; however, at the age of 8, she was referred again complaining of bilateral painless vision loss for 2 years. Her best-corrected visual acuity was 20/100 in the right and 20/125 in the left eye. Pupils were normal in size and reacting to light and accommodation. Intraocular pressure measured by I-care rebound tonometer was 6 and 7 mm of mercury in the right and left eye, respectively. The cycloplegic autorefractometer mean measurements were − 2.5–2.75 × 44 ° in oculus dextrus and − 10.75–8 × 71 ° in oculus sinister.

Anterior-segment examination on the slit lamp revealed inferior corneal steepening in both eyes and stromal scarring in the left eye, bilateral uveal ectropion, and pseudophakia. Anterior-segment optical coherence tomography confirmed inferior corneal steepening and decreased corneal thickness in both eyes with stromal scarring in the left eye [Figure 1]. Posterior-segment examination was normal.{Figure 1}

Corneal tomography [Figure 2] and [Figure 3] revealed an inferior steepening and superior flattening in both eyes, marked thinning in an area coincident with steepening and elevation, increase in I–S ratio (inferior to superior power), abnormal posterior elevation, and significant skewing of the radial axes of the bow tie. We concluded, based on Belin ABCD grading system for keratoconus,[8] that she had a keratoconus Stage A1B0C4D2 − in the right eye and Stage A2B1C4D3 + in the left eye.{Figure 2}{Figure 3}


SOS is a very rare autosomal-recessive disease due to mutation in XYLT2 gene.[4],[5],[6],[7] XYLT2 gene, encoding isoform of xylosyltransferase, impacts on the protein structure and function, modifying expression pattern in different tissues that lead to phenotypic variability.[3] The protein encoded by the XYLT2 gene belongs to a family of glycosyltransferases and regulates proteoglycans' expression such as heparan sulfate and chondroitin sulfate,[3] which are involved in cellular homeostasis, as well as growth factor function, morphogen gradient formation, and coreceptor activity.

As the cornea is composed of an extracellular matrix formed of collagens and proteoglycans, such as dermatan sulfate and keratan sulfate, previous research suggested that keratan sulfate proteoglycans are altered in some corneal diseases such as keratoconus.[9]

Keratoconus is a progressive and asymmetric disorder associated with structural changes in corneal collagen organization and proteoglycans occurring in 1/2000 individuals.[8],[9] Typically, patients complain of progressive visual impairment in the second decade of life due to corneal shape modification, leading to irregular astigmatism, myopia, and poor visual acuity. Frequently, keratoconus is an isolated disease. However, it can be associated with other pathologies or syndromes, for example vernal keratoconjunctivitis, atopy, Down syndrome, retinitis pigmentosa, Leber congenital amaurosis, mitral valve prolapse or connective tissue disorders such as Marfan and Ehlers–Danlos syndromes.[9] Nevertheless, it has never been associated with SOS. In this way, since mutations in XYLT2 gene could affect proteoglycans' expression, and cornea is composed of collagens and proteoglycans; perhaps, mutations in XYLT2 gene could affect corneal composition, favoring the development of structural corneal diseases such as keratoconus.

To the best of our knowledge, this is the first case of bilateral keratoconus in a patient with SOS. Further investigation is needed to clarify the pathogenic mechanisms of SOS and the possible association between these two pathologies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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