Caffey disease, also referred to as infantile cortical hyperostosis, is a self-limiting inflammatory disease of bone, typically diagnosed in infancy (ages less than five months). This disease is characterized by asymmetric, often polyostotic bony hyperostosis and expansion, with a predilection for the mandible (70-90%). We present a unique case of a two-month-old boy with monostotic scapular hyperostosis. The disease is primarily diagnosed on plain film and further evaluated with bone scintigraphy or skeletal survey to identify the extent of osseous involvement. Accompanying MR imaging is not usually obtained due to lack of specificity and diagnostic utility, and when pursued, can potentially confound the diagnosis. MR findings of this case are presented to re-iterate the benignity of this disease process and obviate the need for further invasive procedures.

We report on a female neonate with a clinico-radiological presentation in keeping with a lethal form of prenatal Caffey disease (PCH). She had antenatal and postnatal features of severely bowed long bones, small chest, diaphyseal hyperostosis and polyhydramnios and died shortly after birth. Initial testing excluded COL1A1-related PCH, as an OI gene panel, consisting of COL1A1, COL1A2, CRTAP, and P3H1 genes, was negative. Targeted sequencing using a gene panel was performed and a de novo heterozygous, likely pathogenic variant in IFITM5: c.119C > T(p.Ser40Leu) was identified, which was previously described to cause a severe form of progressively deforming osteogenesis imperfect (OI). To our knowledge, variants in IFITM5 have not been reported in infantile Caffey disease (ICH) or PCH. Given that the pathogenesis of PCH is largely unknown, we postulate that a subset of PCH may be associated with variants in IFITM5.

An inflammatory collagenopathy of infancy characterized by subperiosteal bone hyperplasia is known as infantile cortical hyperostosis (ICH) or Caffey disease. A 10-day male infant presented to the hospital with leg swelling, excessive crying, and irritability since birth. He was born with the swallowed part of his tibia bone. The X-ray suggested hyperostosis of the bilateral tibia bone involving the anterior cortex, which is more prominent on the right side. The infant was clinically monitored and treated and discharged after the swelling was reduced. Again, he was admitted to the hospital at 10 weeks of life, and a similar thickening appeared on his left tibia. He was administered analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) and discharged under a follow-up schedule. The infant was monitored in the pediatric ward for the next seven days. The swelling and pain completely subsided one and a half weeks after hospitalization, and continued follow-up was suggested until the complete correction of the disease on an outpatient basis. This disease must be recognized and understood, and the clinical-radiological correlation is significant.

Caffey disease is a rare and self-limiting condition characterised by cortical hyperostosis with inflammation of adjacent fascia and muscles. It usually presents in infancy and clinical features include hyperirritability, acute inflammation with swelling of overlying soft tissues and subperiosteal new bone formation. Awareness of the existence of this rare condition and its typical clinical and radiological profile will avoid unnecessary investigations and treatment and help the physician to explain its good prognosis to parents of affected children. We report a three-month-old male infant who presented to the Outpatient Paediatrics Department at Moti Lal Nehru Medical College, Allahabad, India, in 2018 with a right shoulder mass, decreased upper limb movements and irritability. The patient was treated with ibuprofen and paracetamol. Irritability and limitation of movement improved over a treatment period of two weeks.

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs.

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.

Type I collagen is an important structural protein of bone, skin, tendon, ligament and other connective tissues. It is initially synthesized as a precursor form, procollagen, consisting of two identical pro-α1(I) and one proα2(I) chains, encoded by COL1A1 and COL1A2, respectively. The N- and C- terminal propeptides of procollagen are cleavage by N-proteinase and C-proteinase correspondingly, to form the central triple helix structure with Gly-X-Y repeat units. Mutations of COL1A1 and COL1A2 genes are associated with osteogenesis imperfecta, some types of Ehlers-Danlos syndrome, Caffey diseases, and osteogenesis imperfect/Ehlers- Danlos syndrome overlapping diseases. Clinical symptoms caused by different variations can be variable or similar, mild to lethal, and vice versa. We reviewed the relationship between clinical manifestations and type I collagen - related rare genetic disorders and their possible molecular mechanisms for different mutations and disorders.

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Caffey disease is a rare condition of early infancy, characterized by soft tissue swelling, bone lesions, and hyperirritability. Its typical radiological finding is periosteal new bone formation. It can be sporadic or inherited in an autosomal dominant manner. There is no specific treatment. In symptomatic cases, non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or naproxen can be used. This is a report of an infant who presented with restlessness, irritability, and swelling over his shins, diagnosed as Caffey disease. Although there was no family history, the genetic analysis revealed heterozygous missense mutation (c.3040C > T) in type-I-collagen-alpha-1-chain gene in the patient in addition to his mother, grandmother, aunt, and cousin. After indomethacin therapy, the complaints of the patient were completely resolved and his bone lesions were significantly improved. This case report is a familial form of Caffey disease from Turkey, with proven heterozygous mutation in the patient and the family members.

A 2-weeks-old Saudi neonate was apparently well till the 10th day of life when a swelling of the right groin was noted accompanied by irritability and fever, without history of trauma. On examination: the girl was irritable and febrile, the mass was firm, ill defined, fixed and tender. The state of the underlying skin was normal. There was family history of 3 siblings with similar swellings in the neonatal period and one of them had recurrence of the condition till the age of 7 year. The radiological findings indicated diaphysis hyperostosis, sparring of the epiphysis and the benign course of the disease. With exclusion of syphilis, osteomyelitis and trauma, the likely diagnosis would be infantile cortical hyperostosis. Such diagnosis should not be overlooked when faced by bony swellings in neonates.