A novel sclerosing skeletal dysplasia with mixed sclerosing bone dysplasia, characteristic syndromic features, and clinical and radiographic evidence of male-male transmission

Abstract

We report on a father and his 4-year-old son sharing a characteristic dysmorphic facial phenotype (including hyperteleroism, prominent forehead, and wide nasal bridge), macrocephaly, hearing loss, palatal clefting, developmental delay, hypotonia and bony abnormalities including marked cranial sclerosis and sclerosis of the ribs and long bones, which evolved in severity in the son between the ages of 2 and 4 years. The father's radiographs also showed prominent coarse striations, patchy metaphyseal sclerotic plaques, markedly increased bone density and cortical thickening of long bones, and significant degenerative changes in the thoracic spine. The son has an additional history of sleep apnea resulting from multi-level airway obstruction that includes adenoid hypertrophy, lingual tonsil hypertrophy, subglottic stenosis, and supra-arytenoid tissue consistent with laryngomalacia and tracheomalacia. The clinical, radiographic, and genetic findings in father and son are consistent with a sclerosing skeletal dysplasia syndrome with similarities to mixed sclerosing bone dysplasia (MSBD) including metaphyseal plaques, osteopathia striata, and cranial sclerosis (OS-CS). This family may represent one of the first descriptions of familial inheritance and evolving phenotype in MSBD. The evidence for male-male transmission would support the existence of an autosomal mechanism of inheritance for a novel form of MSBD with characteristic syndromic features.