Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome.

UNLABELLED: Torg syndrome is a multicentric osteolysis syndrome of unknown etiology. We identified mutations in the MMP2 gene in a patient with Torg syndrome that resulted in complete loss of MMP2 activity. MMP2 mutations were previously identified in patients with NAO and Winchester syndrome. Our findings suggest that Torg, NAO, and Winchester syndrome are allelic disorders. INTRODUCTION: Torg, nodulosis-arthropathy-osteolysis (NAO), and Winchester syndrome are a group of autosomal recessive osteolysis syndromes with marked clinical and radiological overlap. It has been suggested that the three conditions are causally related, but molecular evidence for this assumption has been lacking. Recently, mutations in the matrix metalloproteinase 2 gene (MMP2) have been reported in patients with NAO and Winchester syndrome. MATERIALS AND METHODS: We sequenced the MMP2 gene in a patient with clinical and radiographic findings of Torg syndrome. MMP2 activity was measured with gelatin zymography. RESULTS: Two mutations in the MMP2 gene were identified in this patient. Gelatin zymography indicated complete loss of MMP2 activity. CONCLUSIONS: Torg, NAO, and Winchester syndrome are allelic disorders. The name Torg-Winchester syndrome is suggested as a common denominator for this group of disorders.

Arthropathy of neonatal onset multisystem inflammatory disease (NOMID/CINCA).

BACKGROUND: Neonatal onset multisystem inflammatory disease (NOMID), an autoinflammatory disease, is characterized by fever, chronic urticarial rash, CNS manifestations, and arthropathy. Approximately 50% of patients with NOMID have de novo missense mutations in CIAS1, which is associated with modulation of the IL-1b and apoptotic pathways. Approximately 60% of NOMID patients have prominent arthropathy, most commonly involving the knees, the cause of which remains poorly understood. OBJECTIVE: To more fully describe the findings of NOMID arthropathy on MRI and radiography and to provide a better understanding of the origin of the bony lesions. MATERIALS AND METHODS: We imaged 20 patients with NOMID to further investigate NOMID-associated bony lesions. RESULTS: Bony abnormalities were seen in the knees of 11/20 patients. The knee findings included enlarged, deformed femora and patellae in all and tibiae in the majority, without evidence of synovitis. Some patients had other joint involvement. Most had short stature and valgus or varus knee deformities. No association was noted between bony abnormalities and CIAS1 mutations. The abnormalities appeared to be the result of a mass-producing process. The resulting heterogeneously calcified masses appeared to originate in the physis and deformed the adjacent metaphysis and epiphysis. CONCLUSION: These findings suggest that the arthropathy of NOMID is the result of abnormal endochondral bone growth. Further investigation is needed to determine whether this deformity is triggered by inflammation early in development or by CIAS1 mutations causing abnormal chondrocyte apoptosis.

Lassoed liver: hepatic pseudo-fissure caused by ventriculoperitoneal shunt.

A 2-year-old child with a ventriculoperitoneal shunt and a shunt revision 18 months previously developed a shunt infection. A CT scan of the abdomen was performed soon after the shunt catheter was removed. A peculiar invagination in the liver was demonstrated along the same course of a recently removed intraperitoneal catheter, presumably caused by the catheter. There have been no reported cases of deformity and pseudo-fissure of the liver, which may mimic pathologic processes on ultrasound or CT, caused by a ventriculoperitoneal shunt.

The hand in Smith-Magenis syndrome (deletion 17p11.2): evaluation by metacarpophalangeal pattern profile analysis.

BACKGROUND: Brachydactyly has been described on physical examination in patients with Smith-Magenis syndrome (SMS). Metacarpophalangeal pattern profile analysis (MCPPPA), a method of graphic depiction of the relative size of the bones of the hand, has been used to objectively evaluate radiographs of the hand in patients with SMS in two small series: a single case and a study of four patients. This technique has confirmed brachydactyly and has suggested conflicting MCPPPA results. OBJECTIVE: The purpose of our study was to evaluate the hand by MCPPPA in a large series of patients with SMS. PATIENTS AND METHODS: We measured the bones of the hand and performed MCPPPA in 29 confirmed cases of SMS. RESULTS: Our results in 29 patients demonstrated a different MCPPPA in patients with SMS than previously reported. The analysis confirmed brachydactyly and the previously described trend of more pronounced shortening of the distal bones relative to the more proximal bones, but also demonstrated a previously undescribed pattern: relative enlargement of the proximal phalanx of the thumb and middle phalanx of the fifth finger. However, statistical analysis suggested that the pattern was not highly characteristic. CONCLUSION: MCPPPA of 29 patients with SMS demonstrates a pattern different than previously reported, but not highly characteristic.