RESUMO
A male infant was brought in a paediatric emergency with swelling in the right hand associated with restriction of wrist movements. Examination confirmed similar findings. The history of trauma was not forthcoming. Given the ambiguous history, the possibility of child abuse was kept. X-ray showed local soft tissue swelling with periosteal thickening and raised inflammatory markers in blood tests, which on review of the literature, was consistent with Caffey disease. Due to the self-limiting nature of the condition, the child was managed conservatively. Child abuse should be suspected in children with unexplained injuries, and before labelling abuse, its mimickers should be ruled out.
Assuntos
Maus-Tratos Infantis , Hiperostose Cortical Congênita , Humanos , Lactente , Masculino , Maus-Tratos Infantis/diagnóstico , Hiperostose Cortical Congênita/diagnóstico por imagem , Radiografia , Articulação do PunhoRESUMO
Introducción: La enfermedad de Caffey es una patología ósea inflamatoria, rara, autolimitada, casi exclusiva de lactantes. Objetivos: Jerarquizar el abordaje diagnóstico de una patología poco frecuente. Caso clínico: 4 meses 22 días, varón, consulta por irritabilidad y edema de miembro inferior izquierdo de 4 días de evolución. Sin traumatismos ni fiebre. Examen físico: edema indurado en tercio medio e inferior de pierna izquierda, no rubor ni calor local. Dolor a la palpación de cara anterior y lateral de tibia y peroné. Limitación funcional, no resaltos óseos. Radiografía: engrosamiento del periostio en tibia y peroné a nivel diafisario. Hemograma: Glóbulos blancos 15.380 KU/L, Hemoglobina 10,8 g/dL, Plaquetas 816.400 10/ul, proteína C reactiva 13,90 mg/dl. Con planteo de probable infección osteoarticular se inicia clindamicina ( gentamicina e ingresa a cuidados moderados. Dada la persistencia de edema e irritabilidad, al quinto día se solicita resonancia magnética: hallazgos sugerentes de un probable proceso inflamatorio- infeccioso de partes blandas con compromiso óseo. Completa 14 días de clindamicina y 7 días de gentamicina intravenosa, hemocultivo negativo. Persiste con edema, irritabilidad y dolor. A los 21 días, se revalora la presentación clínica-imagenológica, se plantea enfermedad de Caffey. Se inicia anti-inflamatorio con buena evolución. Conclusiones: La enfermedad de Caffey es una colagenopatía rara, que afecta lactantes. El diagnóstico es clínico - radiológico (irritabilidad, tumefacción de partes blandas y alteraciones radiológicas). El pronóstico a largo plazo suele ser favorable. Es importante considerar el diagnóstico en lactantes que se presentan con esta sintomatología para evitar retrasos diagnósticos e instauración de tratamientos innecesarios.
Introduction: Caffey's disease is a rare disease that is reported almost exclusively in infants. Objective: Describe the case of a rare pathology, prioritizing the diagnostic approach. Clinical case: 4 month -old, healthy male. Consultation due to irritability and edema of the left lower limb for 4 days. No trauma or fever. Physical examination: indurated edema in the left leg, no redness or local heat. Pain on palpation of the anterior and lateral aspect of the tibia and fibula. Functional limitation, no bony protusions. Leg x-ray: thickening of the periosteum in the tibia and fibula at the diaphyseal level. Hemogram: White Blood Cells 15,380 KU/L Hemoglobin: 10.8 g/dL. Platelets: 816,400 10/ul, C-reactive protein: 13.90 mg/dl. He was admitted with a suggestion of probable osteoarticular infection. Clindamycin ( gentamicin is started. Given the persistence of edema and irritability despite treatment, on the fifth day an MRI was requested: findings suggestive of a probable inflammatory-infectious process of soft tissues with bone involvement. Completed 14 days of clindamycin and 7 days of intravenous gentamicin, blood culture negative. It persists with edema, irritability and pain. After 21 days, the clinical-imaging presentation was reassessed and Caffey's disease was considered. Anti-inflammatory begins with good evolution. Conclusions: Caffey's disease is a rare collagenopathy, that affects infants. The diagnosis is clinical - radiological (irritability, soft tissue swelling and radiological alterations). The long-term prognosis is usually favorable. It is important to consider the diagnosis in infants who present with these symptoms to avoid diagnostic delays and initiation of unnecessary treatments.
Introdução: A doença de Caffey é uma patologia óssea inflamatória rara, autolimitada, quase exclusiva de lactentes. Objetivos: Priorizar a abordagem diagnóstica de uma patologia rara. Caso clínico: 4 meses 22 dias, sexo masculino, consulta por irritabilidade e edema do membro inferior esquerdo de 4 dias de evolução. Sem trauma ou febre. Exame físico: edema endurecido em terço médio e inferior da perna esquerda, sem vermelhidão ou calor local. Dor à palpação das faces anterior e lateral da tíbia e fíbula. Limitação funcional, sem saliências ósseas. Radiografia: espessamento do periósteo na tíbia e fíbula ao nível diafisário. Hemograma: Glóbulos brancos 15.380 KU/L, Hemoglobina 10,8 g/dL, Plaquetas 816.400 10/ul, Proteína C reativa 13,90 mg/dl. Com sugestão de provável infecção osteoarticular, foi iniciada clindamicina + gentamicina e internado em cuidados moderados. Dada a persistência do edema e da irritabilidade, no quinto dia foi solicitada ressonância magnética: achados sugestivos de provável processo inflamatório-infeccioso de partes moles com envolvimento ósseo. Completou 14 dias de clindamicina e 7 dias de gentamicina intravenosa, hemocultura negativa. Persiste com edema, irritabilidade e dor. Após 21 dias, o quadro clínico-imagem foi reavaliado e considerada doença de Caffey. O antiinflamatório começa com uma boa evolução. Conclusões: A doença de Caffey é uma colagenopatia rara que afeta lactentes. O diagnóstico é clínico-radiológico (irritabilidade, edema de partes moles e alterações radiológicas). O prognóstico a longo prazo é geralmente favorável. É importante considerar o diagnóstico em lactentes que apresentam esses sintomas para evitar atrasos no diagnóstico e início de tratamentos desnecessários.
Assuntos
Humanos , Masculino , Tíbia/patologia , Hiperostose Cortical Congênita/diagnóstico por imagem , Fíbula/patologia , Dor/etiologia , Edema/etiologia , Inflamação/etiologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Child abuse is a major public health problem that can lead to critical consequences for the child and family. However, early identification of abuse may be difficult. An 8-month-old boy presented with extensive periosteal reaction in both upper and lower long bones. There was no specific history of injury. Caffey disease was initially considered as the diagnosis because the patient displayed fever and hyperostosis of multiple bones with elevated erythrocyte sedimentation rates and C-reactive protein and alkaline phosphatase levels. However, we suspected child abuse based on the clinical and radiological features. We eventually found out that the child had been injured through child abuse and were able to treat him. We report this case because child abuse cases may be confused with Caffey disease. This case report can, therefore, help distinguish between Caffey disease and child abuse.
Assuntos
Maus-Tratos Infantis , Hiperostose Cortical Congênita , Osso e Ossos , Criança , Maus-Tratos Infantis/diagnóstico , Diagnóstico Diferencial , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Lactente , Masculino , RadiografiaRESUMO
Kenny-Caffey syndrome type 2 (KCS2) and osteocraniostenosis (OCS) are allelic disorders caused by heterozygous pathogenic variants in the FAM111A gene. Both conditions are characterized by gracile bones, characteristic facial features, hypomineralized skull with delayed closure of fontanelles and hypoparathyroidism. OCS and KCS2 are often referred to as FAM111A-related syndromes as a group; although OCS presents with a more severe, perinatal lethal phenotype. We report a novel FAM111A mutation in a fetus with poorly ossified skull, proportionate long extremities with thin diaphysis, and hypoplastic spleen consistent with FAM111A-related syndromes. Trio whole exome sequencing identified a p.Y562S de novo missense variant in the FAM111A gene. The variant shows significant similarity to other reported pathogenic mutations fitting proposed pathophysiologic mechanism which provide sufficient evidence for classification as likely pathogenic. Our report contributed a novel variant to the handful of OCS and KCS2 cases reported with pathogenic variants.
Assuntos
Anormalidades Múltiplas/genética , Doenças do Desenvolvimento Ósseo/genética , Anormalidades Craniofaciais/genética , Nanismo/genética , Hiperostose Cortical Congênita/genética , Hipocalcemia/genética , Receptores Virais/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Doenças do Desenvolvimento Ósseo/diagnóstico , Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/patologia , Anormalidades Cardiovasculares/diagnóstico , Anormalidades Cardiovasculares/genética , Anormalidades Cardiovasculares/patologia , Anormalidades Craniofaciais/diagnóstico , Anormalidades Craniofaciais/diagnóstico por imagem , Anormalidades Craniofaciais/patologia , Nanismo/diagnóstico , Nanismo/diagnóstico por imagem , Nanismo/patologia , Ossos Faciais/anormalidades , Ossos Faciais/patologia , Feminino , Feto , Predisposição Genética para Doença , Heterozigoto , Humanos , Hiperostose Cortical Congênita/diagnóstico , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/patologia , Hipocalcemia/diagnóstico , Hipocalcemia/diagnóstico por imagem , Hipocalcemia/patologia , Masculino , Mutação/genética , Gravidez , Crânio/anormalidades , Crânio/patologia , Baço/anormalidades , Baço/diagnóstico por imagem , Sequenciamento do ExomaRESUMO
A 2 month-old female cat, mixed breed, was referred for difficulty moving and severe enlargement of the mandible and limbs. Polyostotic cortical hyperostosis was diagnosed based on diagnostic imaging and histopathological changes of the mandible and limbs. Marked cortical bone thickening was detected on radiographs and CT scan images. The diaphyses of both radii and ulnae, together with the mandibular rami and bodies, were most severely affected. The many similarities shared with the human condition, Caffey's disease, are discussed.
Assuntos
Doenças do Gato , Hiperostose Cortical Congênita , Animais , Doenças do Gato/diagnóstico por imagem , Gatos , Feminino , Seguimentos , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/veterinária , Mandíbula , Radiografia , UlnaRESUMO
Kenny-Caffey Syndrome Type 2 (KCS2) is a rare genetic disorder characterized by short stature, skeletal dysplasia, primary hypoparathyroidism, and delayed closure of the anterior fontanelle. Patients with KCS2 typically require multidisciplinary management due to numerous craniofacial and skeletal anomalies. Craniosynostosis, however, has not yet been identified in a patient with KCS2 to the best of our knowledge. We present the first case of craniosynostosis in the setting of KCS2 and provide a comprehensive analysis of the associated craniofacial findings to date. The authors will describe the craniofacial features specific to our patient and review the characteristic morphological features in a manner relevant to early recognition and focused evaluation.
Assuntos
Nanismo/diagnóstico por imagem , Hiperostose Cortical Congênita/diagnóstico por imagem , Hipocalcemia/diagnóstico por imagem , Crânio/diagnóstico por imagem , Humanos , Hipoparatireoidismo , Lactente , Imageamento por Ressonância Magnética , Masculino , Osteocondrodisplasias , Tomografia Computadorizada por Raios XRESUMO
Caffey disease, or infantile cortical hyperostosis, classically describes a self-limited inflammatory disorder that presents in the infant with fussiness, focal swelling and sometimes fever. Imaging is conventionally limited to radiography, which shows mild to profound subperiosteal bone formation and sometimes deformity. This disease was not uncommonly diagnosed in the late 20th century. Interestingly, the disease may not just occur in the infant, and it may be due to a genetic mutation in the alpha-one chain of type 1 collagen (COL1A1). Recurrent or delayed onset in the older child or adolescent also occurs. In more recent years, another type of inflammatory bone disorder, chronic sterile osteomyelitis, has been frequently recognized and, depending on the radiographic stage or the diagnostic modality used, may have characteristics overlapping with Caffey disease. In this review, we discuss the demographics, imaging and known etiologies for Caffey disease and chronic recurrent multifocal osteomyelitis and raise the possibility of similar molecular origins.
Assuntos
Hiperostose Cortical Congênita/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Osteomielite/diagnóstico por imagem , Radiografia/métodos , Osso e Ossos/diagnóstico por imagem , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , RecidivaRESUMO
Infantile cortical hyperostosis, or Caffey's disease, usually presents with typical radiological features of soft tissue swelling and cortical thickening of the underlying bone. The disease can be fatal when it presents antenatally, especially before a gestational age of 35 weeks. This fatal, premature form of the disease is known to occur in various ethnic groups around the globe, and approximately 30 cases have been reported in English literature. This paper is unique in that it is the first paper to report a lethal form of prenatal-type infantile cortical hyperostosis diagnosed in South Korea. Born at gestational age of 27 weeks and 4 days, the patient had typical features of polyhydramnios, anasarca, hyperostosis of multiple bones, micrognathia, pulmonary hypoplasia, and hepatomegaly. The patient was hypotonic, and due to pulmonary hypoplasia and persistent pulmonary hypertension, had to be supported with high frequency ventilation throughout the entire hospital course. Due to the disease entity itself, as well as prolonged parenteral nutrition, liver failure progressed, and the patient expired on day 38 when uncontrolled septic shock was superimposed. The chromosome karyotype of the patient was normal, 46, XX, and COL1A1 gene mutation was not detected.
Assuntos
Hiperostose Cortical Congênita/patologia , Adulto , Evolução Fatal , Feminino , Idade Gestacional , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Recém-Nascido , Masculino , Gravidez , República da CoreiaRESUMO
We describe radiographic, contrast-enhanced MDCT and MRI findings with pathologic correlations of an unusual recurrence of tumoral calcinosis, also called Teutschlander disease. The disease was silent in the first decade of life, when it appeared with elbows recurring lesions, until the seventh decade of life, when a left hip active growth lesion developed. A review about tumoral calcinosis pathogenesis, clinical course and imaging differential diagnosis is reported. (www.actabiomedica.it).
Assuntos
Calcinose/diagnóstico por imagem , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperfosfatemia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia Computadorizada Multidetectores , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
This report presents two cases of Worth syndrome involving the mandible which were identified as an incidental finding on radiologic evaluation. Both patients were females who presented with enlarged mandibles. Radiologic evaluation revealed multiple bilateral mandibular enostoses, widened and thickened inferior cortical border of the mandible, with no other major clinical finding on examination. One of the patients received orthognathic surgery and healed uneventfully with no post-surgical complications. In this report, we reviewed possible differential diagnoses to this syndrome to facilitate identification among general dentists and oral and maxillofacial radiologists.
Assuntos
Hiperostose Cortical Congênita , Osteopetrose , Osteosclerose , Adulto , Feminino , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Achados Incidentais , Mandíbula/diagnóstico por imagem , Pessoa de Meia-Idade , Osteopetrose/diagnóstico por imagem , Osteosclerose/diagnóstico por imagemRESUMO
Hyperphosphatemic familial tumoral calcinosis (HFTC), secondary to fibroblast growth factor 23 (FGF23) gene mutation, is a rare genetic disorder characterized by recurrent calcified masses. We describe young Lebanese cousins presenting with HFTC, based on a retrospective chart review and a prospective case study. In addition, we present a comprehensive review on the topic, based on a literature search conducted in PubMed and Google Scholar, in 2014 and updated in December 2017. While the patients had the same previously reported FGF23 gene mutation (homozygous c.G367T variant in exon 3 leading to a missense mutation), they presented with variable severity and age of disease onset (at 4 years in patient 1 and at 23 years in patient 2). A review of the literature revealed several potential patho-physiologic pathways of HFTC clinical manifestations, some of which may be independent of hyperphosphatemia. Most available treatment options aim at reducing serum phosphate level, by stimulating renal excretion or by inhibiting intestinal absorption. HFTC is a challenging disease. While the available medical treatment has a limited and inconsistent effect on disease symptomatology, surgical resection of calcified masses remains the last resort. Research is needed to determine the safety and efficacy of FGF23 replacement or molecular therapy, targeting the specific genetic aberration. Hyperphosphatemic familial tumoral calcinosis is a rare genetic disorder characterized by recurrent calcified masses, in addition to other visceral, skeletal, and vascular manifestations. It remains a very challenging disease.
Assuntos
Calcinose/genética , Fatores de Crescimento de Fibroblastos/genética , Hiperostose Cortical Congênita/genética , Hiperfosfatemia/genética , Mutação , Adolescente , Adulto , Densidade Óssea/genética , Calcinose/diagnóstico por imagem , Calcinose/patologia , Ecocardiografia , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/patologia , Hiperfosfatemia/diagnóstico por imagem , Hiperfosfatemia/patologia , Masculino , Linhagem , Estudos Prospectivos , Radiografia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Caffey's disease is a rare syndrome, usually self-limiting, affecting newborn and young infants. On radiological exams, the cortical hyperostosis is always present, associated or not to soft tissue swelling. Other radiographic presentations are described as lytic areas. AIM: This article has the objective to relate computed tomography (CT) findings of Caffey's disease, where lytic lesion on mandibular angle was the principal radiological manifestation. METHODS AND RESULTS: Three-dimensional reconstructions were performed to demonstrate the initial aspect and the healing process. CONCLUSION: This report shows unusual radiological characteristics of Caffey's disease on CT and its progressive resolution.
Assuntos
Hiperostose Cortical Congênita/diagnóstico por imagem , Criança , Diagnóstico Diferencial , Humanos , Imageamento Tridimensional , Masculino , Mandíbula , Radiografia Panorâmica , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Worth syndrome or autosomal dominant endosteal hyperostosis (ADEH) is an extremely rare genetic disease involving increased bone density. To the author's knowledge, this is the second case report of a family with neurologic involvement associated with this condition along with its surgical treatment. The most effective treatment for clinically significant neurologic symptoms in this scenario is currently unknown, and there is sparse experience on surgical treatment for this condition reported in the literature. Therefore we aim to make a contribution to the identification of a standard and consistently successful surgical management. CASE DESCRIPTION: Two patients, mother (Patient 1) and daughter (Patient 2), were diagnosed with Worth syndrome. Both presented with the typical facial characteristics described for ADEH. Interestingly, Patient 1 presented the novel mutation in the LRP5 gene that is associated with different conditions involving increased bone density. Although neurologic symptoms are infrequent in ADEH, both referred chronic headache, nausea, and vomiting. Neuroimaging showed an increased cranial bone density and Chiari I malformation. The patients underwent a midline suboccipital craniectomy with excision of the posterior arch of C1 and duroplasty. However, due to a symptomatic recurrence 5 years after surgery, Patient 1 was reoperated on. We extended the craniectomy and also carried out a C2 laminectomy. CONCLUSION: After surgical interventions, patients' neurologic symptoms were successfully resolved. This report shows that posterior fossa decompression including duroplasty may be a valid treatment option in case of neurologic involvement.
Assuntos
Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/cirurgia , Osteopetrose/diagnóstico por imagem , Osteopetrose/cirurgia , Adolescente , Adulto , Malformação de Arnold-Chiari/complicações , Craniotomia/métodos , Feminino , Humanos , Hiperostose Cortical Congênita/complicações , Osteopetrose/complicações , Resultado do TratamentoRESUMO
Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%. Parathyroid hormone was suppressed (15 pg/mL), associated with a low-normal 25-hydroxyvitamin D (26 ng/mL) concentration but high 1,25-dihydroxyvitamin D concentration (92 pg/mL). Serum intact FGF-23 (fibroblast growth factor 23) was undetectable. Genetic analysis revealed tumoral calcinosis due to a compound heterozygous mutation in FGF23, c.201G>C (p.Gln67His) and c.466C>T (p.Gln156*). Due to lack of other treatment options and because the patient was facing severe vascular complications, we initiated a daily hemodialysis program even in the setting of normal kidney function. This unusual therapeutic option successful controlled hyperphosphatemia and reduced metastatic tumoral lesions. This is a report of a new mutation in FGF23 in which dialysis was an effective treatment option for tumoral calcinosis with normal kidney function.
Assuntos
Calcinose/genética , Calcinose/terapia , Fatores de Crescimento de Fibroblastos/genética , Hiperostose Cortical Congênita/genética , Hiperostose Cortical Congênita/terapia , Hiperfosfatemia/genética , Hiperfosfatemia/terapia , Rim/fisiologia , Mutação/genética , Diálise Renal , Adulto , Calcinose/diagnóstico por imagem , Fator de Crescimento de Fibroblastos 23 , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperfosfatemia/diagnóstico por imagem , Masculino , Diálise Renal/métodos , Resultado do TratamentoRESUMO
Infantile cortical hyperostosis - Caffey-Silverman disease - is a familial disorder manifesting in the late fetal period or infancy with excessive periosteal bone formation. Signs and symptoms regress spontaneously within months and result in expanded, deformed bones. The paucity of clinical symptoms may lead to delayed investigation and confusion of the remaining bone changes with those in other conditions. This problem is exemplified by two siblings misdiagnosed as osteogenesis imperfecta. The diagnosis of Caffey-Silverman disease was confirmed by molecular analysis showing the specific COL1A1 mutation in the patients and their clinically unaffected mother. Reduced penetrance rather than autosomal recessive inheritance explains multiple affected siblings born to healthy parents.
Assuntos
Colágeno Tipo I/genética , Hiperostose Cortical Congênita/diagnóstico , Irmãos , Pré-Escolar , Cadeia alfa 1 do Colágeno Tipo I , Erros de Diagnóstico , Feminino , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/genética , Lactente , Mutação , Osteogênese Imperfeita/diagnósticoAssuntos
Hiperostose Cortical Congênita , Diáfises/diagnóstico por imagem , Diáfises/patologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Humanos , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/genética , Hiperostose Cortical Congênita/patologia , Lactente , Radiografia , Tíbia/diagnóstico por imagem , Tíbia/patologiaRESUMO
The autosomal dominant form of Caffey disease is a largely self-limiting infantile bone disorder characterized by acute inflammation of soft tissues and localized thickening of the underlying bone cortex. It is caused by a recurrent arginine-to-cysteine substitution (R836C) in the α1(I) chain of type I collagen. However, the functional link between this mutation and the underlying pathogenetic mechanisms still remains elusive. Importantly, it remains to be established as to how a point-mutation in type I collagen leads to a cascade of inflammatory events and spatio-temporally limited hyperostotic bone lesions, and how structural and inflammatory components contribute to the different organ-specific manifestations in Caffey disease. In this review we attempt to shed light on these questions based on the current understanding of other mutations in type I collagen, their role in perturbing collagen biogenesis, and consequent effects on cell-cell and cell-matrix interactions.