Unclassified sclerosing bone dysplasia with osteopathia striata, cranial sclerosis, metaphyseal undermodeling, and bone fragility

Abstract

Sclerosing bone dysplasias are diagnosed on the basis of a characteristic pattern of osteosclerosis and clinical manifestations; in many of them, cause and pathogenesis are still unknown. A 33-year-old man had five fractures of the humerus, tibiae, and femur as a result of mild traumatic incidents that occurred between the ages of 18 and 33 years as well as a remnant of rib fractures without apparent trauma on radiographs. His height was 158 cm (-2.2 SD). Radiographic evaluation showed cranial sclerosis, longitudinal striations in the metaphyses of the femur and tibia, fan-like striation in the ilium, metaphyseal widening in the femur and tibia, and sclerosis of the ribs. The blood chemistry findings, including serum calcium, phosphorus, and alkaline phosphatase, were normal. Biopsy from the ilium showed thick trabeculae composed of woven bone. The coexistence of osteopathia striata, cranial sclerosis, metaphyseal undermodeling, and bone fragility has not been recognized previously. Our case appears to represent a new form of sclerosing bone dysplasia.

WTX R353X mutation in a family with osteopathia striata and cranial sclerosis (OS-CS): case report and literature review of the disease clinical, genetic and radiological features

“…OS-CS has been classically considered an autosomal dominant condition with high penetrance and variable intra- and interfamilial expressivity [4,9,12,15-17,21,43] until the recent identification of mutated WTX (Wilms Tumor in the X; also called FAM123B and AMER1 ) within proximal Xq11.2 in affected families [8]. WTX can be spliced: the full length form encodes for a 1135 aminoacid protein, WTXs1, which possesses three binding sites for APC (adenomatous polyposis coli), a β-catenin- (C-terminal), a WT1- and a PIP2 (phosphatidylinositol 4.5 bisphosphate, at N-terminus)- binding site; and a shorter isoform, WTXs2 (missing aminoacids 50-326) keeps the first APC- binding domain [45-47].…”

“…Osteopathia striata with cranial sclerosis (OS-CS; OMIM#300373) is a rare, X-linked dominant inherited skeletal dysplasia (prevalence 0.1/1 million people [1]), part of sclerosing bone dysplasias [2-4], a group of disorders characterized by abnormally dense bones as a result of the prevalence of bone formation by osteoblasts over bone reabsorption by osteoclasts. Striated methaphyses were firstly described by Voorhoeve in 1924 [5]; thirty years later, Hurt [3] reported a case of association with cranial sclerosis.…”

“…Age at diagnosis and clinical presentation is highly variable, ranging from asymptomatic to neonatal lethal cases. Skull thickening, responsible for characteristic facies, and linear striations in the metaphyseal region of the long bones and pelvis represent disease main features, the latter representing a key feature for differential diagnosis [2-4]. Nervous and internal organs defects can be associated.…”

Temporal Bone CT Findings in a Male Patient with Osteopathia Striata and Cranial Sclerosis

“…However, the clinical pattern of partial involvement, as well as the reported family observations pleads for X-linked inheritance with mild striated bone affections to carrier women and severe syndromic morbidity and high mortality to the males [1,17]. Descriptions of biochemical findings and biopsy changes in patients having osteopathia striata with cranial sclerosis are scarce [6,12,15].…”

Osteopathia striata with cranial sclerosis (OSCS): review of the literature and case report demonstrating challenges of spinal fusion after trauma

“…Elevated bone density has been found in the pelvis and trunk of OSCS patients [15]. Another patient with OSCS has been described as having fractures of the humerus, tibia, and femur as a result of mild traumatic incidents [12]. In this paper, we report a case of a patient with OSCS presenting with trauma following motor vehicle collision.…”