Spondyloocular Syndrome: A Report of an Additional Family and Phenotypic Spectrum Delineation

Abstract

Spondyloocular syndrome (SOS, OMIM # 605822) is a rare genetic disorder characterized by osseous and ocular manifestations, including generalized osteoporosis, multiple long bones fractures, platyspondyly, dense cataracts and retinal detachment, and dysmorphic facial features, with or without short stature, cardiopathy, hearing impairment, and intellectual disability. Biallelic mutations in the XYLT2 gene (OMIM * 608125), encoding the xylosyltransferase II, were shown to be responsible for this disease. To date, 22 cases with SOS have been described, with varying clinical presentations and a yet-to-be-established genotypic-phenotypic correlation. Two patients from a consanguineous Lebanese family that presented with SOS were included in this study. Whole exome sequencing revealed a novel homozygous nonsense mutation in XYLT2 (p.Tyr414*) in these patients. We review all previously reported cases with SOS, describe the second nonsense mutation in XYLT2, and contribute to a better delineation of the phenotypic spectrum of the disease.

Keywords: Lebanon; XYLT2; ocular disorders; skeletal disorders; spondyloocular syndrome; whole exome sequencing.

Figure 1

Pedigree of the reported family. Black color represents the affected individuals. Arrows indicate the affected individuals included in this study.

Figure 2

X-rays of patient 1 showing thinning of the occipital bone, abnormal vertebrae, kyphoscoliosis, femoral fractures, and bone demineralization.

Figure 3

X-rays of patient 2. Note the abnormal lower dorsal and lumbar vertebra and the femoral fracture.

Figure 4

Electrophoregrams showing the identified p.Tyr414* (c.1242C>A) variant in XYLT2 (NM_022167.3), in the affected patient (IV-4).