Bruck Syndrome
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《美国医学杂志》
Department of Pediatrics, Kalawati Saran Children's Hospital, Lady Hardinge Medical College, New Delhi, India, India
Abstract
Abstract. The combination of arthrogryposis multiplex congenita and osteogenesis imperfecta is extremely rare. This combination is named Bruck syndrome. A 34 week male baby weighing 1.7 kg at birth was noted to have multiple flexion contractures and pterygia at elbows, wrists and knees, in addition to right foot talipes equinovarus deformity. Postnatally the child developed multiple swellings involving both the upper and lower limbs. A plain radiograph revealed the presence of fractures involving the long bones of the upper and lower limbs. A diagnosis of osteogenesis imperfecta with arthrogryposis multiplex congenita was made, and the patient was labeled as a case of Bruck Syndrome. The aim of this report is to make the readers aware regarding this rare entity and to specifically look for presence of features suggestive of osteogenesis imperfecta when encountered with a neonate born with arthrogryposis multiplex congenita. [Indian J Pediatr 2005; 72 (5) : -442]
Keywords: Arthrogryposis; Osteogenesis imperfecta; Bruck syndrome; Neonate
Arthrogryposis multiplex congenita is a syndrome characterized by the presence of congenital contractures of the multiple joints usually with flexion deformities, with or without pterygia or webbing at the joints involved. Osteogenesis imperfecta or "brittle bone disease" is a rare disorder of connective tissue involving the bones, ligaments, tendons, skin and sclera, and characterized by bone fragility and pathological fractures of long bones, blue sclera, thin skin, joint laxity, hernias, wormian bones, and secondary skeletal deformities. The disease is heritable and characterized by abnormality in the synthesis of Type I collagen, which is present in the bone matrix.
The combination of arthrogryposis multiplex congenita and osteogenesis imperfecta is extremely rare.[1] This combination is named "Bruck syndrome", after the discoverer of the first case noticed in 1897. The aim of this report is to sensitize the readers about this rare disorder and to also help them in managing these children so as to prevent them from developing serious disability.
Case Report
0A 34 week preterm male baby was born to a 26 year old second gravida mother by spontaneous vaginal delivery out of a non consanguineous marriage. The antenatal period was uneventful. The child at birth weighed 1.7 kg (<25th centile), and was noted to have deformed limbs, with bilateral flexion contractures and pterygia at elbows, and bilateral flexion contractures at wrists and knees (Fig 1). Right foot was noted to have talipes equinovarus deformity. An initial diagnosis of arthrogryposis multiplex congenita was made. The baby was nursed in the neonatal unit for the subsequent 2 days when he was noticed to have multiple swellings involving the legs and hands. These swellings were tender and had superficial bruising provisional diagnosis of pathological fractures was made and an infantogram was obtained.The infantogram revealed the presence of multiple fractures, involving bilateral humeral shafts, bilateral tibia-fibula in the legs, right femoral shaft, and multiple old rib fractures with callus formation (Fig 2). Also noted were wormian bones in the skull.The baby had white sclera. An additional diagnosis of osteogenesis imperfecta were made. A bone and skin biopsy was declined by the father of the child. No abnormalities of any other internal organs was detected. Specific inquiry regarding the presence of a similar disorder in the family or relatives yielded a negative result.
Discussion
Bruck syndrome is a very rare disorder characterized by the association of osteogenesis imperfecta and arthrogryposis multiplex congenita.The first case was described by Bruck in 1897.[2] This is the second report of this syndrome from India, the first case reported by Sharma and Anand in 1964.[3] The disease occurs both sporadically as well as in an autosomal recessive manner. As there was no family history suggestive of a similar disorder, the mode of inheritance seems most likely due to a sporadic mutation in this case. Bruck syndrome has been classified in the Third International Nomenclature of Constitutional Disorders of the Skeleton 1998,[1] under two categories of OI with congenital joint contractures, in the nomenclature of OI syndromes. Type 1 includes those cases of Bruck syndrome that result from mutations in the gene for terminal lysyl hydroxylase I (TLH I) located on chromosome 17q. TLH I is involved in the registration of type I collagen polypeptides prior to assembly of the triple helices. This type of the disease follows an autosomal inheritance. Those cases of Bruck syndrome in which this linkage could not be demonstrated are possibly linked to another locus; such cases are classified under Type 2. Thus there are at least two loci for Bruck syndrome.
However, it is important to note that molecular diagnosis is, at present not available in most of the centres and is of little help to characterize clinical severity and prognosticate evolution. Hence, a good clinical evaluation remains of utmost importance to delineate the basic abnormalities associated with this disorder.
Clinically most of these patients present with congenital contractures and pterygia. They mostly have white sclera as in this case and normal hearing and vision. The fractures occur postnatally and the contractures are the primary abnormality and not a complication of the fractures. Fractures also occur in isolated arthrogryposis without associated osteogenesis imperfecta (Bruck syndrome) due to osteoporosis but they are never as severe and frequent as seen in a case of Bruck syndrome. We were not able to examine the bone specimen from this patient due to refusal of consent for bone biopsy from the parents. Brenner et al[4] performed the electron microscopy of the bone specimen of affected patient and showed the presence of osteoblasts with swollen mitochondria and dilated endoplasmic reticulum. They also noted a decrease in the diameter of the collagen fibrils along with low mineral content and increased pepsin extraction of collagen 1.
The disease progresses relentlessly in all patients and leads to severe limb deformities, short stature, progressive kyphoscoliosis and multiple fractures. While meticulous orthopedic care with fracture management and rehabilitation remain the cornerstones in the management of all types of OI, bisphosphonates have been shown to be safe and effective in treatment of osteoporosis in several types of OI, including Bruck syndrome. Cyclic intravenous pamidronate is now the gold standard of treatment of Bruck syndrome. Side effects are rare, and include first dose fever and occasional nephrocalcinosis. Response to therapy can be monitored via bone densitometric studies. Oral bisphophonates, such as alendronate and risedronate are currently undergoing clinical trials for establishing their safety and efficacy.[1]
Most of the patients are of normal intelligence with normal hearing and vision. This patient is presently 1 month old and has been thriving well, he has subsequent to discharge suffered from two fractures involving the lower limbs and continues to be in regular orthopedic care.
The main purpose of this case report, besides reporting a very rare entity was to make the reader aware that whenever confronted by a neonate with features suggestive of arthrogryposis multiplex congenita, an immediate radiological assessment should be done to rule out underlying osteogenesis imperfecta. This would not only aid in promptly identifying this rare disorder but also help in instituting early preventive modalities to prevent further fractures from occurring like gentle handling, padding of beds and splinting etc. Early orthopedic consultation would be routinely required for most of these patients to help them in rehabilitation and recovery. Arthrogryposis can be picked up antenatally on ultrasound from the second trimester onwards. With the discovery of the specific gene locus and biochemical defect, in future it may be possible to identify such fetuses in utero and offer specific genetic counseling
References
1. Sillence DO. Disorders of bone density,volume and mineralisation. In Emery and Rimoins, eds. Principles and Practice of Medical Genetics . Vol.3 4th edn. Philadelphia; Churchill Livingstone, 2002; 4116-4126.
2. Bruck A.Ueber eine seltene Form von Erkrankung der Knochen und Gelenke. Dtsch Med Wochenschr 1897; 23: 152-155.
3. Sharma NL, Anand JS. Osteogenesis imperfecta with arthrogryposis multiplex congenita. Indian Med J 1964; 53 : 124-126.
4. Brenner RE, Vetter U, Stoss H, Muller PK, Teller WM. Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures. Eur J Pediatr 1993; 152 : 505-508(Datta Vikram, Sinha Aditi)
Abstract
Abstract. The combination of arthrogryposis multiplex congenita and osteogenesis imperfecta is extremely rare. This combination is named Bruck syndrome. A 34 week male baby weighing 1.7 kg at birth was noted to have multiple flexion contractures and pterygia at elbows, wrists and knees, in addition to right foot talipes equinovarus deformity. Postnatally the child developed multiple swellings involving both the upper and lower limbs. A plain radiograph revealed the presence of fractures involving the long bones of the upper and lower limbs. A diagnosis of osteogenesis imperfecta with arthrogryposis multiplex congenita was made, and the patient was labeled as a case of Bruck Syndrome. The aim of this report is to make the readers aware regarding this rare entity and to specifically look for presence of features suggestive of osteogenesis imperfecta when encountered with a neonate born with arthrogryposis multiplex congenita. [Indian J Pediatr 2005; 72 (5) : -442]
Keywords: Arthrogryposis; Osteogenesis imperfecta; Bruck syndrome; Neonate
Arthrogryposis multiplex congenita is a syndrome characterized by the presence of congenital contractures of the multiple joints usually with flexion deformities, with or without pterygia or webbing at the joints involved. Osteogenesis imperfecta or "brittle bone disease" is a rare disorder of connective tissue involving the bones, ligaments, tendons, skin and sclera, and characterized by bone fragility and pathological fractures of long bones, blue sclera, thin skin, joint laxity, hernias, wormian bones, and secondary skeletal deformities. The disease is heritable and characterized by abnormality in the synthesis of Type I collagen, which is present in the bone matrix.
The combination of arthrogryposis multiplex congenita and osteogenesis imperfecta is extremely rare.[1] This combination is named "Bruck syndrome", after the discoverer of the first case noticed in 1897. The aim of this report is to sensitize the readers about this rare disorder and to also help them in managing these children so as to prevent them from developing serious disability.
Case Report
0A 34 week preterm male baby was born to a 26 year old second gravida mother by spontaneous vaginal delivery out of a non consanguineous marriage. The antenatal period was uneventful. The child at birth weighed 1.7 kg (<25th centile), and was noted to have deformed limbs, with bilateral flexion contractures and pterygia at elbows, and bilateral flexion contractures at wrists and knees (Fig 1). Right foot was noted to have talipes equinovarus deformity. An initial diagnosis of arthrogryposis multiplex congenita was made. The baby was nursed in the neonatal unit for the subsequent 2 days when he was noticed to have multiple swellings involving the legs and hands. These swellings were tender and had superficial bruising provisional diagnosis of pathological fractures was made and an infantogram was obtained.The infantogram revealed the presence of multiple fractures, involving bilateral humeral shafts, bilateral tibia-fibula in the legs, right femoral shaft, and multiple old rib fractures with callus formation (Fig 2). Also noted were wormian bones in the skull.The baby had white sclera. An additional diagnosis of osteogenesis imperfecta were made. A bone and skin biopsy was declined by the father of the child. No abnormalities of any other internal organs was detected. Specific inquiry regarding the presence of a similar disorder in the family or relatives yielded a negative result.
Discussion
Bruck syndrome is a very rare disorder characterized by the association of osteogenesis imperfecta and arthrogryposis multiplex congenita.The first case was described by Bruck in 1897.[2] This is the second report of this syndrome from India, the first case reported by Sharma and Anand in 1964.[3] The disease occurs both sporadically as well as in an autosomal recessive manner. As there was no family history suggestive of a similar disorder, the mode of inheritance seems most likely due to a sporadic mutation in this case. Bruck syndrome has been classified in the Third International Nomenclature of Constitutional Disorders of the Skeleton 1998,[1] under two categories of OI with congenital joint contractures, in the nomenclature of OI syndromes. Type 1 includes those cases of Bruck syndrome that result from mutations in the gene for terminal lysyl hydroxylase I (TLH I) located on chromosome 17q. TLH I is involved in the registration of type I collagen polypeptides prior to assembly of the triple helices. This type of the disease follows an autosomal inheritance. Those cases of Bruck syndrome in which this linkage could not be demonstrated are possibly linked to another locus; such cases are classified under Type 2. Thus there are at least two loci for Bruck syndrome.
However, it is important to note that molecular diagnosis is, at present not available in most of the centres and is of little help to characterize clinical severity and prognosticate evolution. Hence, a good clinical evaluation remains of utmost importance to delineate the basic abnormalities associated with this disorder.
Clinically most of these patients present with congenital contractures and pterygia. They mostly have white sclera as in this case and normal hearing and vision. The fractures occur postnatally and the contractures are the primary abnormality and not a complication of the fractures. Fractures also occur in isolated arthrogryposis without associated osteogenesis imperfecta (Bruck syndrome) due to osteoporosis but they are never as severe and frequent as seen in a case of Bruck syndrome. We were not able to examine the bone specimen from this patient due to refusal of consent for bone biopsy from the parents. Brenner et al[4] performed the electron microscopy of the bone specimen of affected patient and showed the presence of osteoblasts with swollen mitochondria and dilated endoplasmic reticulum. They also noted a decrease in the diameter of the collagen fibrils along with low mineral content and increased pepsin extraction of collagen 1.
The disease progresses relentlessly in all patients and leads to severe limb deformities, short stature, progressive kyphoscoliosis and multiple fractures. While meticulous orthopedic care with fracture management and rehabilitation remain the cornerstones in the management of all types of OI, bisphosphonates have been shown to be safe and effective in treatment of osteoporosis in several types of OI, including Bruck syndrome. Cyclic intravenous pamidronate is now the gold standard of treatment of Bruck syndrome. Side effects are rare, and include first dose fever and occasional nephrocalcinosis. Response to therapy can be monitored via bone densitometric studies. Oral bisphophonates, such as alendronate and risedronate are currently undergoing clinical trials for establishing their safety and efficacy.[1]
Most of the patients are of normal intelligence with normal hearing and vision. This patient is presently 1 month old and has been thriving well, he has subsequent to discharge suffered from two fractures involving the lower limbs and continues to be in regular orthopedic care.
The main purpose of this case report, besides reporting a very rare entity was to make the reader aware that whenever confronted by a neonate with features suggestive of arthrogryposis multiplex congenita, an immediate radiological assessment should be done to rule out underlying osteogenesis imperfecta. This would not only aid in promptly identifying this rare disorder but also help in instituting early preventive modalities to prevent further fractures from occurring like gentle handling, padding of beds and splinting etc. Early orthopedic consultation would be routinely required for most of these patients to help them in rehabilitation and recovery. Arthrogryposis can be picked up antenatally on ultrasound from the second trimester onwards. With the discovery of the specific gene locus and biochemical defect, in future it may be possible to identify such fetuses in utero and offer specific genetic counseling
References
1. Sillence DO. Disorders of bone density,volume and mineralisation. In Emery and Rimoins, eds. Principles and Practice of Medical Genetics . Vol.3 4th edn. Philadelphia; Churchill Livingstone, 2002; 4116-4126.
2. Bruck A.Ueber eine seltene Form von Erkrankung der Knochen und Gelenke. Dtsch Med Wochenschr 1897; 23: 152-155.
3. Sharma NL, Anand JS. Osteogenesis imperfecta with arthrogryposis multiplex congenita. Indian Med J 1964; 53 : 124-126.
4. Brenner RE, Vetter U, Stoss H, Muller PK, Teller WM. Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures. Eur J Pediatr 1993; 152 : 505-508(Datta Vikram, Sinha Aditi)