Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: Clinical and radiographic delineation of a pleiotropic disorder

• Published in: American journal of medical genetics. Part A 2006-03, Vol.140A (6), p.541-550
• Main Authors: Renella, Raffaele, Schaefer, Elke, LeMerrer, Martine, Alanay, Yasemin, Kandemir, Nurgun, Eich, Georg, Costa, Teresa, Ballhausen, Diana, Boltshauser, Eugen, Bonafé, Luisa, Giedion, Andres, Unger, Sheila, Superti-Furga, Andrea
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - diagnostic imaging; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Adolescent; Adult; Biological and medical sciences; Bone and Bones - abnormalities; Bone and Bones - diagnostic imaging; Brain Diseases - pathology; Calcinosis - pathology; cerebral calcification; Child; Child, Preschool; Diseases of the osteoarticular system; enchondroma; Family Health; Female; Humans; immune dysregulation; Immune System Diseases - pathology; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; immunodeficiency; Immunopathology; Male; Medical sciences; Muscle Spasticity - pathology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Osteochondrodysplasias - pathology; Pedigree; Radiography; skeletal dysplasia; spasticity; spondyloenchondrodysplasia; Tumors of striated muscle and skeleton
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31081

Enchondromas are a feature of several constitutional disorders of bone, and the classification of different nosologic entities is still provisional. Among these disorders, spondyloenchondrodysplasia (SPENCD), as outlined by Schorr et al. [1976], is defined by the presence of radiolucent spondylar and metaphyseal lesions that represent persistence of islands of chondroid tissue within bone. Careful review of radiographic findings is needed to distinguish SPENCD from the many other disorders combining enchondromas with spinal lesions. Even when strict criteria are applied, it appears that SPENCD is clinically heterogeneous, as some SPENCD patients are neurologically intact while others present with spasticity, mental retardation, and cerebral calcifications in different combinations, and it has been suggested that SPENCD should be divided in two types. We herein report ten individuals from six families with SPENCD and illustrate the radiographic changes. Seven individuals had CNS manifestations including spasticity, developmental delay, and late‐onset cerebral calcifications. We also noted that six individuals had clinical manifestations of autoimmunity (auto‐immune thrombocytopenic purpura, auto‐immune hemolytic anemia, auto‐immune thyroiditis, and SLE) and one had been diagnosed with immune deficiency. Neurological and autoimmune manifestations were seen in different combinations within one single family. These observations suggest that SPENCD may be a single entity defined by specific radiographic features, but with remarkably pleiotropic manifestations that include CNS disease (spasticity, mental retardation, and calcifications), as well as immune dysregulation ranging from autoimmunity to immunodeficiency. The notion of recessive inheritance hitherto assumed is challenged by the observation of two apparently dominant pedigrees. © 2006 Wiley‐Liss, Inc.