Radiographic Manifestations in Pfeiffer Syndrome

Abstract

The patient, a 14-year-old boy with type 1 Pfeiffer syndrome and a 2-month history of pain in the fourth finger of his left hand, was referred to the rheumatology clinic. The patient presented at birth with craniosynostosis, hypertelorism, and brachydactyly. The geneticists diagnosed Pfeiffer syndrome, and gene testing confirmed a mutation in fibroblast growth factor receptor 1. His clinical history and disease course included hearing loss, initial speech delay (now resolved), dental problems, and malocclusion. In addition to his symptoms of finger pain, he also had intermittent subluxation of his left elbow and both shoulders due to congenital dislocations. Excluding joint pain, the patient denied any other symptoms of inflammatory arthritis. There was no family history of rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, or psoriasis. The musculoskeletal physical examination was remarkable for short broad fingers and toes, decreased range of motion in both the first and second digits, and decreased range of motion in both elbows and shoulders. Radiographs of two views of the hands and wrists showed partial fusion at the first interphalangeal joints bilaterally and the second proximal interphalangeal (PIP) joint of the left hand. The second PIP joint of the right hand was completely fused. The proximal phalanges of the thumb and the middle phalanges of the second and fourth fingers were shortened bilaterally. Both thumbs were radially deviated. The metacarpal heads of both hands also appeared slightly diminutive. There was widening at the distal radioulnar joints, with the ulna appearing abnormally rotated on the frontal view bilaterally, which indicates instability at the radioulnar joint. Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that affects 1 in 100,000 persons. The syndrome is a result of mutations in fibroblast growth factor receptors 1 or 2 leading to gain-of-function altered cell differentiation, including bone cells. There is no association with an inflammatory or autoimmune mechanism. Musculoskeletal involvement in Pfeiffer syndrome is commonly associated with craniosynostosis, maxillary hypoplasia, broad and deviated thumbs and great toes, and partial syndactyly of the hands and feet in addition to joint fusion and ankylosis of small and large joints. The diagnosis of Pfeiffer syndrome is essentially clinical, but radiologic exploration can confirm the associated skeletal abnormalities (1-3). This patient was referred to the rheumatology clinic in order to rule out arthritis. Clinical examination did not reveal the typical findings of inflammatory arthritis but only the musculoskeletal findings described above. Although radiology provided no explanation for the pain in the fourth finger of his left hand, this digit may be in the early stages and a new site for bone formation and ultimate fusion. Serial radiographs can be helpful to document disease progression. Because the process is noninflammatory in nature, magnetic resonance imaging is not indi...