Gorham-Stout Disease

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

G6PC, SLC37A4, PHKA2, APOB, APOE, BTD, SI, ABCG8, MGAM, GCA, PYGM, ROS1, HNF1A, TRAF3, SMUG1, ADRA2A, NT5C3A, CDHR5, MED18, ABCG5, POLDIP3, LINC01193, H3P36, PYGL, MB, MNAT1, GBE1, APRT, CCKAR, CSF2

G6PC, SLC37A4, PHKA2, APOB, APOE, BTD, SI, ABCG8, MGAM, GCA, PYGM, ROS1, HNF1A, TRAF3, SMUG1, ADRA2A, NT5C3A, CDHR5, MED18, ABCG5, POLDIP3, LINC01193, H3P36, PYGL, MB, MNAT1, GBE1, APRT, CCKAR, CSF2, CSF3, CTLA4, CYP7A1, FABP2, GH1, MFAP1, GNAS, GYG1, GYS2, IL6ST, LAMC2, LRPAP1, ANXA2, H3C9P

Drugs

Ethanol (96 per cent ) (gel for injection), Streptococcus pyogenes Su strain cells treated with benzylpenicillin

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Gorham-Stout disease (GSD) is a rare disease of massive osteolysis associated with proliferation and dilation of lymphatic vessels. GSD may affect any bone in the body and can be monostotic or polyostotic. Symptoms at presentation are dependent upon the location(s) of the disease; the most common symptom is localized pain. The disease may be discovered after a pathological fracture.

Epidemiology

To date around 300 cases have been reported in the literature. GSD does not display a clear race, sex predilection (1.6:1; male: female ratio) or geographic distribution.

Clinical description

GSD can present at any age, but is commonly diagnosed in children and young adults (average 13 years). GSD may affect any bone in the body but most commonly affects the ribs, followed by the cranium, clavicle and cervical spine. Additional affected areas include maxillofacial bones (mostly the mandible), sternum, humerus, hand, femur, and foot. GSD can be monostotic or polyostotic and symptoms vary according to the body sites affected. The most common symptom is localized pain. Swelling, weakness and functional impairment of affected limbs are also noticed. In the dentoalveolar region, mobile teeth, malocclusion, mandibular deviation and bony deformity may be observed. Patients with thoracic involvement may present respiratory distress (caused by chylothorax). Severe neurological defects and paralysis, secondary to vertebral involvement, are also observed. Patients with cervical spine or base of skull disease can develop cerebrospinal fluid leak. GSD may be discovered after a bone fracture (spontaneous or following minor trauma).

Etiology

Etiology of GSD is still elusive. The pathological process is the benign vascular proliferation of endothelial channels adjacent to or within bone, leading to extreme thinning of bony trabecula, osteoclast-mediated resorption, and replacement of bone with fibrous tissue. Tissue samples test positive for lymphatic endothelial cell markers, suggesting that GSD is a disease involving disordered lymphangiogenesis.

Diagnostic methods

Diagnosis relies on radiographic findings revealing progressive osteolysis and cortical destruction. Magnetic resonance imaging shows complete resorption of bone and replacement with infiltrative soft tissue that is of low signal intensity on T1-weighted imaging and high signal intensity on T2, with intense enhancement on contrast imaging. Immunohistochemical markers of lymphatic endothelial cells (LYVE-1, podoplanin/D2-40) reveal presence of lymphatic vessels in medullary and cortical regions of bones, and in affected soft tissues. Rib lesions should not be biopsied, as this procedure may elicit a refractory chylous effusion.

Differential diagnosis

Differential diagnosis includes generalized lymphatic anomaly (the major distinguishing characteristic is the progressive osteolysis seen in GSD), acroosteolysis dominant type, multicentric carpo-tarsal osteolysis with or without nephropathy, autosomal recessive carpotarsal osteolysis, hereditary sensory and autonomic neuropathy type 2, Farber lipogranulomatosis, Torg-Winchester syndrome, and idiopathic phalangeal acro-osteolysis (see these terms). Other causes of osteolysis such as infection, cancer (primary or metastatic), inflammatory or endocrine disorders should also be considered.

Genetic counseling

GSD occurs sporadically.

Management and treatment

Treatment of GSD includes drugs (bisphosphonates and/or interferon alpha 2b, sirolimus is also being studied) to stabilize progressive disease, and supportive procedures that may reduce or halt chylothorax (pleurectomy, pleurodesis, thoracentesis, and thoracic duct embolization or ligation), or may stabilize affected regions of the skeleton. Radiotherapy may be used in combination with these therapies, but is generally reserved for refractory or rapidly progressive disease.

Prognosis

Prognosis depends on the extent and location of affected areas. Mild disease may remain stable for many years, while severe cases involving the craniofacial and/or thoracic areas may be fatal. Pulmonary involvement may herald a worsened prognosis.