CASE REPORT |
https://doi.org/10.5005/jojs-10079-1136 |
Caffey Disease: Genetically Proven Case Report of 2-month-old Indian Infant
1–4Department of Pediatrics, Maulana Azad Medical College and Associated Lok Nayak Hospital, Delhi, India
Corresponding Author: Deepak Kumar, Department of Pediatrics, Maulana Azad Medical College and Associated Lok Nayak Hospital, Delhi, India, Phone: +91 9211377848, e-mail: deepakk70@gmail.com
Received: 09 October 2023; Accepted: 12 December 2023; Published on: 12 January 2024
ABSTRACT
Caffey disease, or infantile cortical hyperostosis, is a rare genetic disorder characterized by abnormal bone formation and swelling of limbs in infants. This case report provides a detailed description of a 2-month-old male infant presenting with deformities of the hands and feet, along with swelling and restricted movement of the limbs. Genetic testing confirmed a mutation in the COLA1A gene, confirming the diagnosis of Caffey disease. The report discusses the clinical presentation, diagnostic evaluation, management, and follow-up of the patient, emphasizing the need for regular monitoring and further research to improve understanding and treatment options for this rare condition.
How to cite this article: Ram V, Kumar K, Rajeshwari K, et al. Caffey Disease: Genetically Proven Case Report of 2-month-old Indian Infant. J Orth Joint Surg 2024;6(1):82–83.
Source of support: Nil
Conflict of interest: None
Keywords: Caffey disease, Case report, Children, COL1A1 mutation, Congenital, India, Infantile cortical hyperostosis, Musculoskeletal abnormalities, Pediatric
INTRODUCTION
Caffey disease, also referred to as infantile cortical hyperostosis, is a rare genetic syndrome characterized by acute inflammation of the diaphyseal periosteum of the long bones, mandibles, scapulas, and overlying soft tissues leading to swelling, prolonged fever, excessive crying and irritability in young infants. Caffey disease is a self-limiting syndrome that typically presents within 4–5 months of life and resolves spontaneously by 2 years of age.
It was first reported by Caffey and Silverman in 1945 and has since been recognized as a distinct clinical entity.1 It is inherited in an autosomal dominant manner, with mutations identified in the COLA1A gene, which encodes the alpha chain of type I collagen. The abnormal collagen synthesis leads to the formation of hyperostotic lesions and inflammation in the affected bones.2 Although the exact etiology and pathogenesis of Caffey disease are not fully understood, it is believed to involve dysregulation of bone remodeling and inflammatory processes.
Diagnostic evaluation involves a combination of clinical assessment, radiographic imaging, laboratory investigations, and genetic testing. Radiological changes like subperiosteal reaction, cortical thickening, and new bone formations can also be seen in infectious or noninfectious inflammatory bone diseases such as osteomyelitis, tumors, child abuse, chronic hypervitaminosis A, scurvy, malignant infantile osteopetrosis.3 Hence, the identification of COLA1A mutation mandates confirmation of the diagnosis of Caffey disease.
We are reporting a genetically proven case from India with confirmed pathological mutation—COLA1A gene: c.3040C>T [p.Arg1014Cys] was used to establish the diagnosis of Caffey disease. The case highlights its existence and makes pediatricians and orthopedic surgeons aware of this relatively rare, clinically debilitating, but self-limiting condition seen in young infants.
CASE DESCRIPTION
A 2-month-old male infant was admitted to a tertiary level healthcare hospital in Northern India with the chief complaints of swelling and deformities in the left upper limb and lower limb noticed since the 10th day of life. The deformity was described as abnormal curvature of the distal part of arms and legs, along with swelling over the corresponding areas. The swelling was noted to be increasing in size gradually and also started to appear in other limbs similarly after 2–3 weeks. Over the last 2 weeks, the parents have also noticed fullness on the right lower side of the face. There is a significant history of non-consolable crying while touching and moving the affected limbs. There are no significant medical or genetic problems in the family.
At presentation, the baby was alert, and vitals were stable. There was no pallor, icterus, lymph node enlargement, or rashes over the body. The head shape was normal, the circumference was 42.5 cm, and there was no facial dysmorphology. In upper limbs, there was swelling in the distal right arm with angular deviation deformity of right wrist and hand (Fig. 1). The movement on the right wrist and left ankle was extremely painful and restricted. There was anterior bowing of the distal part of the lower limb on both sides, more pronounced on left side, with overlying swelling on the affected parts (Fig. 1). The swelling was also noted over the right mandibular arch. There was no restriction in mouth opening. Other system examinations were unremarkable.
Investigations: hemoglobin—9.8 mg/dL, total leukocyte counts—16,800 cells per cumm, differential leukocytes—P 78%, L 20%, M 4%, platelet counts—5.8 lacs per cumm, erythrocyte sedimentation rate—58 mm/hour, C-reactive protein—15 mg/dL. Biochemical parameters: Blood urea—20 mg/dL, serum creatinine—0.4 mg/dL, serum sodium—144 mmol/L, serum potassium—4.2 mmol/L, serum bilirubin (Total/Direct)—0.8 mg/dL/0.2 mg/dL, serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase—280/40, total protein—7.8 gm/dL, serum albumin 4.0 gm/dL. Calcium total—9.8 mg/dL, ionized—1.1 mmol/L, phosphates—5.5 mg/dL, alkaline phosphatase—580 IU/L. High-performance liquid chromatography of hemoglobin was normal, and sickling test was negative. Maternal serology for syphilis (Venereal Disease Research Laboratory) was negative.
Skeleton survey showed an intense periosteal reaction with mild sclerotic changes with decreased bone density of the right ulna. There was associated increase in soft tissue opacity above ulna (Fig. 2). Similarly, subperiosteal thickening and calcification were seen on bilateral tibia, more evident on the left side, leading to anterior bowing deformity (Fig. 2).
Based on the above skeleton radiological findings and the characteristic age of onset of these typical symptoms, a diagnosis of hyperostotic cortical bone disease (Caffey disease) was kept. The genetic test (Sanger sequencing) showed presence of a pathological mutation in COLA1A gene:c.3040C>T [p.Arg1014Cys], confirming the diagnosis.
DISCUSSION
The clinical presentation of our patient aligns with the characteristic features of Caffey disease. Our patient presented with the typical symptoms of fever, irritability, and swellings/deformities of the limbs. Mandible being the most common site of swelling seen in over 70% of cases, our patient had left mandibular arch swelling along with the involvement of long bones.3
Our radiographic findings are in accordance with the diagnostic criteria established for Caffey disease in previously reported literatures.4 However, the close mimickers of the disease, such as Ewing sarcoma, osteomyelitis, or child abuse, may present similarly where genetic testing becomes essential to prove the diagnosis. In our case, the diagnosis was confirmed through the identification of a mutation in the COLA1A gene. There are only a few cases identified in literature where the diagnosis is confirmed by reporting mutation in COLA1A gene.
Though it is a self-limiting disorder, bony affliction in young infants can cause significant mental and psychosocial burdens to the caregivers. Hence, parental education and counseling regarding the disease’s nature and progression are of paramount importance.
Management of Caffey disease focuses on symptomatic relief and supportive care. In our case, the primary goal was to alleviate discomfort and minimize crying episodes through the administration of pain relief (paracetamol). Regular follow-up visits were scheduled to monitor disease progression, assess the resolution of existing lesions, and detect the appearance of new ones. Reports are available where naproxen/indomethacin has been tried and seems to be effective; the hypothetical theory of prostaglandin-induced bony changes was thought behind the trial of prostaglandin inhibitors in a few reports only.5 However, the age at which naproxen was started in these reports was the age at which the bony swelling starts to regress by itself (1–2 years).
Our case represents a unique contribution to the literature as it is probably the second reported case from India where the diagnosis of Caffey disease was confirmed genetically. This highlights the importance of genetic testing in confirming the diagnosis and the need for increased awareness and research in this field.
REFERENCES
1. Caffey J, Silverman W. Infantile cortical hyperostosis, preliminary report of a new syndrome. Am J Roentgenol Radiat Ther 1945;54:1–16.
2. Gensure RC, Mäkitie O, Barclay C, et al. A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. J Clin Invest 2005;115(5):1250–1257. DOI: 10.1172/JCI22760
3. Mazzolari E, Forino C, Razza A, et al. A single-center experience in 20 patients with infantile malignant osteopetrosis. Am J Hematol 2009;84(8):473–479. DOI: 10.1002/ajh.21447
4. Gorlin RJ, Cohen MM, Levin LS. Syndromes of the Head and Neck, 4th edition. Oxford University Press; 2001. pp. 153–157.
5. Thometz JG, DiRaimondo CA. A case of recurrent Caffey disease treated with naproxen. Clin Orthop 1996;323:304–309. DOI: 10.1097/00003086-199602000-00043
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