11/251. Familial cryptic translocation between chromosomes 2qter and 8qter: further delineation of the Albright hereditary osteodystrophy-like phenotype. Recently five patients with an Albright hereditary osteodystrophy (AHO)-like phenotype were reported to have a subtelomeric deletion of the long arm of chromosome 2. These patients showed a striking resemblance to a number of patients from a large pedigree known to us for a long time. After molecular confirmation of a subtelomeric deletion in one patient, FISH analysis was used and a cryptic translocation between the long arms of chromosomes 2 and 8, t(2;8)(q37.3;q24.3), was detected. Remarkably, five proven and 10 probable cases with a 2qter deletion were found in the family, but none with an 8qter deletion. This was not explained by increased fetal loss. The major clinical characteristics of terminal 2q deletion are a short, stocky build, round face, sparse hair, deeply set eyes, bulbous nose, thin vermilion border, brachymetaphalangism, seizures, and developmental delay. A specific behavioural phenotype consisting of periods of hyperkinesia and aggression can develop with age. The overall phenotype is sufficiently characteristic to allow clinical recognition. The cytogenetic and molecular studies did not narrow down the common deleted region. Both testing of additional 2q markers and characterisation of other AHO-like patients with 2q37 microdeletions may help to define the candidate gene region. ( info) |
12/251. Cranio-facial fibrous dysplasia in a 38-year-old African woman: a case history. A 38-year-old woman sought treatment with cranio-facial dysplasia involving the cranium, maxilla and the mandible. Her chief complaint was a mandibular swelling, which had appeared about 2 years previously, had gradually enlarged, and was associated with spontaneous pain. x-ray film examination revealed a ground-glass opacity with blurred demarcation and a 99 Tc medronate bone scan disclosed an increase in tracer uptake in the cranium, maxilla and mandible. The rest of the skeleton was not affected. Histological examination of the lesions revealed solid proliferation of spindle-shaped cells associated with islands of osteid and bone trabecullae with Chinese letter pattern and numerous multinucleated giant cells consistent with fibrous dysplasia. The continued osteoblastic activity of involved bones, coupled with the medical condition of the patient, restricted the management of the patient to largely supportive and palliative care. ( info) |
13/251. Identification of two novel deletion mutations within the Gs alpha gene (GNAS1) in Albright hereditary osteodystrophy. Albright hereditary osteodystrophy (AHO) is a genetic disorder characterized by short stature, skeletal defects, and obesity. Within AHO kindreds, some affected family members have only the somatic features of AHO [pseudopseudohypoparathyroidism (PPHP)], whereas others have these features in association with resistance to multiple hormones that stimulate adenylyl cyclase within their target tissues [pseudohypoparathyroidism type Ia (PHP Ia)]. Affected members of most AHO kindreds (both those with PPHP and those with PHP Ia) have a partial deficiency of Gs alpha, the alpha-subunit of the G protein that couples receptors to adenylyl cyclase stimulation, and in a number of cases heterozygous loss of function mutations within the Gs alpha gene (GNAS1) have been identified. Using PCR with the attachment of a high melting domain (GC-clamp) and temperature gradient gel electrophoresis, two novel heterozygous frameshift mutations within GNAS1 were found in two AHO kindreds. In one kindred all affected members (both PHP Ia and PPHP) had a heterozygous 2-bp deletion in exon 8, whereas in the second kindred a heterozygous 2-bp deletion in exon 4 was identified in all affected members examined. In both cases the frameshift encoded a premature termination codon several codons downstream of the deletion. In the latter kindred affected members were previously shown to have decreased levels of GNAS1 messenger ribonucleic acid expression. These results further underscore the genetic heterogeneity of AHO and provides further evidence that PHP Ia and PPHP are two clinical presentations of a common genetic defect. Serial measurements of thyroid function in members of kindred 1 indicate that TSH resistance progresses with age and becomes more evident after the first year of life. ( info) |
14/251. A rare case of polyostotic fibrous dysplasia assessed by bone scintigraphy with Tc-99m methylene diphosphonate (MDP). A 66-year-old man affected by polyostotic form of fibrous dysplasia in consequence of worsening of lower extremity bone pain aggravated by walking and concomitant increase of serum alkaline phosphatase and osteocalcin, was subjected first to a radionuclide study. Bone scan demonstrated a pathological uptake of the radiotracer in the craniofacial bones, right scapula, left and right posterior ribs, right hemipelvis and lower extremities confirming the diagnosis but establishing especially the extent of bone involvement, greater than expected on the basis of symptoms and X-ray findings, underlying the importance of nuclear medicine imaging in the assessment and follow-up of this rare disease. ( info) |
| McCune-Albright syndrome (MAS) is a disease of noninheritable, genetic origin defined by the triad of cafe-au-lait pigmentation of the skin, precocious puberty, and polyostotic fibrous dysplasia. This syndrome, which affects young girls primarily, has also been reported with other endocrinopathies, and rarely with acromegaly and hyperprolactinemia. The fibrous dysplasia in MAS is of the polyostotic type and, apart from the characteristic sites such as the proximal aspects of the femur and the pelvis, the craniofacial region is frequently involved. A male patient with MAS presented with juvenile gigantism, precocious puberty, pituitary adenoma-secreting growth hormone and prolactin, hypothalamic pituitary gonadal and thyroid dysfunction, and polyostotic fibrous dysplasia causing optic nerve compression. Visual deterioration and its surgical management are presented. ( info) |
16/251. osteosarcoma in a patient with McCune-Albright syndrome and Mazabraud's syndrome. Sarcomas infrequently develop in osseous sites of fibrous dysplasia. We report a patient with Mazabraud's syndrome (polyostotic fibrous dysplasia and soft tissue myxomas) complicated by the development of osteogenic sarcoma in a bone affected by fibrous dysplasia. This is the third case of osteosarcoma within the small population of reported patients with Mazabraud's syndrome. There may be an increased incidence of malignant transformation in these individuals' dysplastic bones above that associated with patients suffering from fibrous dysplasia alone. ( info) |
17/251. Bilateral proptosis: an unusual presentation of fibrous dysplasia. Fibrous dysplasia is a benign, developmental bone disorder of unknown aetiology. With involvement of the facial bones, indications for surgical intervention include cosmetic deformity and/or progressive neurological dysfunction. We present the case of a 36-year-old female with bilateral orbital lesions whose initial presentation was that of progressive proptosis and visual loss. She underwent bilateral pterional craniotomies with gross total resection of her tumours. review of the literature reveals several cases of unilateral orbital fibrous dysplasia. This appears to be the first reported case of distinct, bilateral orbital fibrous dysplasia. ( info) |
18/251. McCune-Albright syndrome with fibrous dysplasia of the paranasal sinuses. We report a 19-year old female patient with the McCune-Albright syndrome, which is a rare disease consisting of polyostotic fibrous dysplasia (FD) of bone associated with brown pigmented areas of the skin and several endocrine dysfunctions. The patient had FD involving the paranasal sinuses, the middle turbinate and the skull. The endocrine dysfunction of the patient concerns both growth hormone and prolactin hypersecretion. Because the patient had no major symptoms, neither surgical nor medical treatment was applied. Five-year follow-up revealed no complication and enlargement of the lesion. ( info) |
19/251. Familial polyostotic fibrous dysplasia. A case of polyostotic fibrous dysplasia of the craniofacial type is presented, together with substantial evidence that this condition had a genetic basis in this patient. A review of the literature indicates that there is absolutely no previous evidence of a genetic basis to this condition. The possibility that the propositus suffered from polyostotic fibrous dysplasia of the Jaffe or the Albright type was excluded. ( info) |
20/251. Segmentary fibrous dysplasia manifesting as macrodactyly. In this report we describe the unusual manifestation of fibrous dysplasia of rays IV and V of the right hand and of rays III-IV of the left hand in a 12-year-old normal girl. The first symptoms of localised macrodactyly became progressively evident from the age of 8 years on. ( info) |