Idiopathic familial acroosteolysis: Histomorphometric study of bone and literature review of the Hajdu‐Cheney syndrome

Abstract

We describe a 27-year-old man with familial acroosteolysis involving 9 fingers. Bone biopsy of an affected digit showed osteolysis with no tetracycline deposition, rare osteoclasts, increased vascularity, and numerous mast cells. In contrast, the iliac crest bone showed active ,bone remodeling and normal doubletetracycline labeling. We believe mast cells deserve further study as possible factors in this form of localized osteolysis.Idiopathic acroosteolysis is an uncommon disorder which involves painful osteolysis of the distal phalanges. When it occurs in a familial form, with a characteristic facies, generalized osteoporosis, and early loss of teeth (l), the condition is termed HajduChencey syndrome. We describe a patient and his mother: the fifth family reported to have this disorder. for the first time in this syndrome. The non-decalcified iliac crest bone biopsy specimen showed active bone remodeling features.Case report. The patient was a 27-year-old white man with a 7-year history of gradually progressive deformity in 9 fingers and loss of distal phalangeal mass. He had continuous pain in the tips of all involved fingers. He denied having Raynaud's phenomenon, frostbite, or burns, or having been exposed to ergot, vinyl chloride, or trauma. He had no history of acute or chronic arthritis, myalgias, skin rash, tight skin, or symptoms in his feet. Graves' disease had been diagnosed 2 years after the onset of his hand symptoms. This had been treated successfully with 1311, 2 years previously; however hypothyroidism had evolved and was being controlled with levothyroxine sodium, 0.1 mg daily. In addition, he was taking diazepam, 5 mg 3 times daily. He also had impotence, noted approximately since the diagnosis of thyroid disease.The patient's mother had similar "shrinking fingers," which first appeared approximately at age 50, progressed for 2 years, then became asymptomatic and have remained stable for the past 15 years. His father had normal hands, and had died at age 64 of lung cancer. The patient has 2 sisters, ages 37 and 38, who are in good health without musculoskeletal problems.The patient was short, with a broad face and prominent eyebrows (Figure 1). His temperature was 98"F, pulse rate 68/minute, blood pressure 110/70, respirations 16/minute, weight 162 lbs, and height 66 inches. He had slight proptosis, but extraocular muscle and funduscopic examination results were normal. He had numerous caries, but all his teeth were

Hajdu–Cheney syndrome with severe dural ectasia

“…It has been speculated that osteoporosis in adults with HCS is secondary to a failure of bone mass accretion during puberty [Leidig-Bruckner et al, 1999]. However, histological, histomorphometric, and biochemical findings as well as the progressive nature of osteoporosis suggest that increased bone turnover and increased bone resorption play a significant role [Udell et al, 1986;Nunziata et al, 1990;Leidig-Bruckner et al, 1999;Drake et al, 2003]. Bisphosphonate treatment with alendronate [Drake et al, 2003] as well as combined pamidronate and teriparatide treatment [McKiernan, 2008] have been used occasionally in HCS patients with promising results.…”

Hajdu Cheney Mouse Mutants Exhibit Osteopenia, Increased Osteoclastogenesis, and Bone Resorption

“…Despite the pronounced skeletal abnormalities reported in Hajdu Cheney syndrome, little is known regarding the mechanisms underlying the bone loss or the effects of Notch2 gain-of-function in the skeleton. Information obtained from iliac crest bone biopsies has been inconclusive and reported in a small number of subjects with Hajdu Cheney syndrome (32)(33)(34)(35).…”

“…Despite the pronounced skeletal abnormalities reported in Hajdu Cheney syndrome, little is known regarding the mechanisms underlying the bone loss or the effects of Notch2 gain-of-function in the skeleton. Information obtained from iliac crest bone biopsies has been inconclusive and reported in a small number of subjects with Hajdu Cheney syndrome (32)(33)(34)(35).The purpose of this work was to gain understanding on the Hajdu Cheney syndrome skeletal phenotype and the mechanisms involved. To this end, we created a mouse model reproducing the NOTCH2 mutation (6949C3 T) found in a subject affected by the disease and presenting with pronounced osteoporosis and fractures (28,30 …”

Primary sjogren's syndrome associated with systemic necrotizing vasculitis: a fatal case

“…." (1). This observation, whether applied to their patient, who had the familial form of the disorder, or to Elias' patient, who had the nonfamilial form (2), is at best a truism.…”

“…She died on the thirty-ninth day of hospitalization. Sjogren's syndrome (SS) is an autoimmune exocrinopathy with highly variable systemic clinical features (1). Since the prognosis is generally good in patients with primary SS, there have been few autopsy reports.…”