Cranio-lenticulo-sutural dysplasia (CLSD), also known as Boyadjiev-Jabs syndrome, is a rare autosomal recessive syndrome manifesting with large and late-closing fontanels, hypertelorism, early-onset cataract and mild generalized skeletal dysplasia. Affected patients have abnormal hair, frontal bossing, hyperpigmentation with capillary hemangioma of the forehead, macrocephaly, significant hypertelorism, and a broad and prominent nose.
CLSD was first reported in 21 members of a Saudi family. Treatment is mainly symptomatic and the prognosis is good.
Boyadjiev et al. (2003) and Boyadjiev et al. (2006) reported a highly inbred Saudi family of Bedouin descent with 21 members. In two related clusters within the family in which parents were double first cousin, five males and one female were affected with a new dysmorphic syndrome. All affected members had similar craniofacial features including wide open calvarial sutures with large and late-closing anterior fontanels, frontal bossing, hyperpigmentation, with capillary hemangioma of the forehead, significant hypertelorism, and a broad and prominent nose. All affected individuals also had a posterior Y-shaped sutural cataract diagnosed at 1 to 2 years of age. In addition, they had skeletal abnormalities including, membranous bones of the calvaria, but vertebral and pelvic bone defects and generalized joint hypermobility. Genetic mapping assigned CLSD to chromosome 14q21.1, and the SEC23A gene was found to be the causative gene. In fibroblasts from individuals affected with CLSD, a gross dilatation of the endoplasmic reticulum was demonstrated by electron microscopy and immunofluorescence. These cells also exhibited cytoplasmic mislocalization of SEC31. In 2011, Boyadjiev et al. (2011) reported a 4.5-year-old boy with CLSD who had a characteristic facial appearance as well as clinical and skeletal features similar to those of the original patients described by Boyadjiev et al. (2003). While most of the patients diagnosed in both studies had common facial features, the eye phenotypes differed, with esotropia, bilateral optic atrophy, and double-ring sign of the lens present in the new case, but no cataract detected by 4.5 years of age. Other previously undescribed features included macrocephaly, anterior frenulum linguae requiring frenulectomy, bifid uvula, cleft palate, gastroesophageal reflux with postnatal failure to thrive, valvular pulmonic stenosis, and osteopenia.