Camurati-Engelmann disease (progressive diaphyseal dysplasia) in a Moroccan family

ArticleinOsteoporosis International 16(9):1167-70 · October 2005with12 Reads
DOI: 10.1007/s00198-005-1896-2 · Source: PubMed
We report on a 46-year-old mother of Moroccan origin, suffering mainly from painful, swollen legs, and her 26-year-old son who had experienced intense pain in his legs, without fever, for approximately 3 years. They did not have dysmorphic features or abnormal gaits. Radiographic studies of the mother revealed diaphyseal sclerosis of the tibia and spondylosis of the thoracal and lumbar vertebrae. The son had sclerosis of the diaphyses of the metacarpalia of the left hand, the femur and the fibula. The other parts of the skeleton were normal. Several osteosclerotic/hyperostotic disorders, such as melorheostosis (present mostly in sporadic cases and affecting lower extremities) and van Buchem's disease (autosomal recessive and commonly affecting the mandible) were considered as a diagnosis in the proposita. However, similar symptoms in the son of the proposita suggested an autosomal dominant inheritance pattern. This brought us to the diagnosis of progressive diaphyseal dysplasia (PDD) or Camurati-Engelmann disease (CED), an autosomal dominant disorder characterized by limb pain, reduced muscle mass, weakness, a waddling gait, progressive periosteal and endosteal sclerosis of the diaphyses of the long bones and sclerosis of the skull base. Mutations in the transforming growth factor (TGF)-beta1 gene on chromosome 19q13.1 have been reported to cause this disorder. The diagnosis of PDD/CED in this family was confirmed at the molecular level by detection of a C-to-T transition at position 466, leading to an arginine-to-cysteine amino acid change (position 156) in exon 2 of the transforming growth factor-beta1 (TGFB1) gene.
    • "Sur le plan radiologique, l'atteinte osseuse est symétrique et bilatérale, aboutissant à un rétrécissement de la cavité médullaire par un épaississement corticale endosté et périosté de la diaphyse des os longs. Au niveau du crâne, on observe une condensation et une hyperostose de la base du crâne [69] qui peuvent entraîner des sténoses foraminales responsables de compressions nerveuses : des déficits des nerfs crâniens (surdité, troubles visuels et paralysie faciale notamment) sont présents chez 38 % des patients [86, 87] . "
    [Show abstract] [Hide abstract] ABSTRACT: De nombreuses affections congénitales ou acquises peuvent être à l'origine d'ostéocondensations ou d'hyperostoses de la voûte et de la base du crâne. En pratique quotidienne, le scanner ou l'imagerie par résonance magnétique (IRM) deviennent les principaux modes de découverte de ce type de pathologie. Les seules indications restantes de la radiographie du crâne concernent essentiellement le bilan osseux général classiquement réalisé dans certaines hémopathies et dans les maladies osseuses constitutionnelles de l'enfant. Les explorations scintigraphiques du squelette, en fournissant une étude concomitante du crâne, permettent aussi d'avoir une analyse du métabolisme des os du crâne. Le but de ce travail est donc de décrire les caractéristiques radiologiques des ostéocondensations et des hyperostoses crâniennes en fonction du caractère locorégional ou généralisé de l'atteinte osseuse.
    Full-text · Chapter · Jan 2016 · Journal of Korean medical science
    • "Marrow space can contain increased interstitial fibrosis.(15) Osteoid osteoma or chronic osteomyelitis have been diagnosed in CED.(65,66) In 2007, Bondestam et al.(27) reported iliac crest histology (following tetracycline labeling) of a 10-year-old boy with CED that featured trabecular osteoporosis with normal bone remodeling. "
    [Show abstract] [Hide abstract] ABSTRACT: We report a 32-year-old man and his 59-year-old mother with a unique and extensive variant of Camurati-Engelmann disease (CED) featuring histopathological changes of osteomalacia and alterations within TGFβ1 and TNFSF11 encoding TGFβ1 and RANKL, respectively. He suffered leg pain and weakness since childhood and reportedly grew until his late 20s, reaching 7 feet in height. He had deafness, perforated nasal septum, torus palatinus, disproportionately long limbs with knock-knees, low muscle mass, and pseudoclubbing. Radiographs revealed generalized skeletal abnormalities, including wide bones and cortical and trabecular bone thickening in keeping with CED, except that long bone ends were also affected. Lumbar spine and hip BMD Z-scores were + 7.7 and + 4.4, respectively. Biochemical markers of bone turnover were elevated. Hypocalciuria accompanied low serum 25-hydroxyvitamin D (25[OH]D) levels. Pituitary hypogonadism and low serum insulin-like growth factor (IGF)-1 were present. Karyotype was normal. Despite vitamin D repletion, iliac crest histology revealed severe osteomalacia. Exon 1 of TNFRSF11A (RANK), exons 2, 3, and 4 of LRP5, and all coding exons and adjacent mRNA splice junctions of TNFRSF11B (OPG), SQSTM1 (sequestosome 1), and TNSALP (tissue nonspecific alkaline phosphatase) were intact. His asymptomatic and less dysmorphic 5'11″ mother, also with low serum 25(OH)D, had milder clinical, radiological, biochemical, and histopathological findings. Both individuals were heterozygous for a novel 12-bp duplication (c.27_38dup, p.L10_L13dup) in exon 1 of TGFβ1, predicting four additional leucine residues in the latency-associated-peptide segment of TGFβ1, consistent with CED. The son was also homozygous for a single base transversion in TNFSF11, predicting a nonconservative amino acid change (c.107C > G, p.Pro36Arg) in the intracellular domain of RANKL that was heterozygous in his nonconsanguineous parents. This TNFSF11 variant was not found in the SNP Database, nor in published TNFSF11 association studies, but it occurred in four of the 134 TNFSF11 alleles (3.0%) we tested randomly among individuals without CED. Perhaps the unique phenotype of this CED family is conditioned by altered RANKL activity.
    Full-text · Article · May 2011
    • "Camurati-Engelmann disease (CED) (Mendelian Inheritance in Man 131300), also known as progressive diaphyseal dysplasia (PDD), is a rare disease that occurs in both genders with equal frequency and is inherited in an autosomal dominant pattern with variable penetrance and wide expressivity (1-3). Considerable variations in signs, symptoms, and severity between afflicted individuals exist within the same family (2, 3). The main clinical symptoms are pain in the legs, waddling gait, muscular weakness, and easy fatigability (1-3). "
    [Show abstract] [Hide abstract] ABSTRACT: Camurati-Engelmann disease (CED) is an autosomal dominant progressive diaphyseal dysplasia caused by mutations in the transforming growth factor-beta1 (TGFB1) gene. We report the first Korean family with an affected mother and son who were diagnosed with CED. The proband is a 19-yr-old male with a history of abnormal gait since the age of 2. He also suffered from proximal muscle weakness, pain in the extremities, and easy fatigability. Skeletal radiographs of the long bones revealed cortical, periosteal, and endosteal thickenings, predominantly affecting the diaphyses of the upper and lower extremities. No other bony abnormalities were noted in the skull and spine and no remarkable findings were seen on laboratory tests. The patient's mother had a long-standing history of mild limb pain. Under the impression of CED on radiographic studies, we performed mutation analysis. A heterozygous G to A transition at cDNA position +653 in exon 4 of the TGFB1 gene (R218H) was detected in the patient and his mother.
    Full-text · Article · Sep 2009
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