A report of three patients with MMP2 associated hereditary osteolysis

Summary: A report of three patients with MMP2 associated hereditary osteolysis: Osteolysis syndromes are rare hereditary disorders characterized by destruction and resorption of affected bones. The current study adds three new patients from (wo unrelated consanguineous families with a severe form of inherited osteolysis. Clinical examination. radiological, biochemical, ultrastructural and molecular studies were conducted. Clinical and radiological studies suggested the diagnosis of Torg- Winchester syndrome. The three affected patients were homozygous for novel MMP2 gene mutations which confirmed the diagnosis. Our patients arc the first lo be reported from Egypt thus, supporting the pan ethnic nature of the disease. Key-words: Hereditary osteolysis -Torg-Winchesler syndrome - Novel MMP2 gene mutations. INTRODUCTION Osteolysis disorders are a group of inherited diseases characterized by rheumatoid like destruction and resorption of affected small joints with associated swelling and pain. Historically, the existence of three autosomal recessive osteolysis syndromes was suspected: Torg syndrome, Winchester syndrome and Nodulosis-Arthropathy-Osteolysis syndrome (NAO) or Multicentric Osteolysis Nodulosis and Arthropathy (MONA). (OMIM respectively are: 259600, 277950, 605 1 56) ( 1 8), As they are all caused by MMP2 mutations, they were grouped under the nomenclature of Torg- Winchester syndrome (TWS) (OMIM: 259600) (18). The current study reports three new patients from two unrelated Egyptian families with Torg-Winchester syndrome. CLINICALREPORTS FAMILY 1 Patient 1 A 17-year old female patient was referred to our department because of hand and feet deformities and difficulty in walking. The patient was the oldest child of first cousin parents; she had a younger brother who was similarly affected and a healthy sister. Pregnancy, delivery and early childhood were uneventful. At the age of 4.5 years, her mother noticed that her right leg was shorter than the left. Painless swellings of fingers and toes developed. The patient was diagnosed with juvenile rheumatoid arthritis (JRA) and received non-steroid anti-inflammatory medications with no improvement. Fractures of right tibia and left radius occurred following trauma when the patient was 6, 8 and 9 years old. At 1 1 years of age, the condition progressed to involve the large joints, particularly the wrist, knee and ankle joints. On examination (at 17 years of age) the patient had mild coarse facies, low anterior hair line, slightly prominent eyes, narrow nasal bridge, bulbous nose and full cheeks. The neck was short with symmetrically thickened, hyperpigmented skin. The patient had mild hirsuitism. Orodental examination showed right facial hemihypertrophy and gum hypertrophy. Growth and development were normal for age. Upper limb examination showed bilateral limited range of movement at the shoulder joint, while elbow and wrist joints showed flexion deformity with limited extension. Fingers of both hands were short and swollen with constriction rings between phalanges due to scalloping of soft tissues covering the shortened bones (Fig. IB). Metacarpophalangeal and proximal inter-phalangeal joints showed fixed extension while distal interphalangeal joints showed flexion deformity. Skin pads at the palmar surface of terminal phalanges were noted. Examination of lower limbs showed limited extension of both knee joints, both feet were broad and short, all toes were swollen and severely shortened and knob-like with constriction rings between the phalanges and a wide gap between the hallux and other toes. Large painless fibrocollagenous pads at the soles were seen (Fig. IE). Radiological examination showed marked osteoarthritic changes of wrist and knee joints. Long bones showed marked osteopenia. X-ray of hands and feet showed marked osteoporosis of metacarpal and metatarsal bones, cortical thinning and medullary expansion. …