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Revista Paulista de Pediatria : Orgao... 2024To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal...
OBJECTIVE
To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T).
CASE DESCRIPTION
A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications.
COMMENTS
MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature.
Topics: Humans; Female; Mutation, Missense; Lamin Type A; Child; Phenotype; Mandible; Lipodystrophy; Acro-Osteolysis
PubMed: 38808865
DOI: 10.1590/1984-0462/2024/42/2022189 -
Clinical Rheumatology Jul 2024
Topics: Humans; Acro-Osteolysis; Scleroderma, Systemic; Female; Middle Aged; Radiography
PubMed: 38767709
DOI: 10.1007/s10067-024-06988-3 -
Diagnostics (Basel, Switzerland) Mar 2024Hand impairment is a frequently reported complaint in systemic sclerosis (SSc) patients and a leading cause of disability and diminished quality of life. Managing hand...
Hand impairment is a frequently reported complaint in systemic sclerosis (SSc) patients and a leading cause of disability and diminished quality of life. Managing hand pain can be particularly challenging due to the coexistence of non-inflammatory arthralgias, inflammatory arthritis, acro-osteolysis, tenosynovitis, joint contractures, tendon friction rubs, nerve entrapment, Raynaud's phenomenon (RP), digital ulcers (DU), sclerodactyly, calcinosis, and chronic pain. While physical examination and radiographs are the first line methods for evaluating hand pain, they are limited in scope and miss many underlying etiologies of hand impairment. We propose a joint ultrasound (US) hand protocol to differentiate between various articular, periarticular, ischemic, skin, and nerve pathologies and to assist in targeted treatment strategies.
PubMed: 38611582
DOI: 10.3390/diagnostics14070669 -
European Journal of Medical Genetics Jun 2024Hajdu-Cheney syndrome (HCS) is an extremely rare autosomal dominant skeletal disorder. The prevalence rate of less than 1 case per 1,000,000 newborns and only 50 cases...
Hajdu-Cheney syndrome (HCS) is an extremely rare autosomal dominant skeletal disorder. The prevalence rate of less than 1 case per 1,000,000 newborns and only 50 cases were reported in the medical literature. HCS is characterized by progressive bone resorption in the distal phalanges (acro-osteolysis), progressive osteoporosis, distinct craniofacial changes, dental anomalies, and occasional association with renal abnormalities. HCS is caused by pathogenic variants in the NOTCH2 gene, 34th exon. We report first familial case of HCS caused by likely pathogenic variant of NOTCH2 gene c.6449delC, p.(Pro2150LeufsTer5).
Topics: Humans; Hajdu-Cheney Syndrome; Receptor, Notch2; Male; Female; Lithuania; Pedigree
PubMed: 38580081
DOI: 10.1016/j.ejmg.2024.104938 -
Cureus Mar 2024Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is an uncommon autosomal recessive disorder caused by a mutation in the uroporphyrinogen III...
Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is an uncommon autosomal recessive disorder caused by a mutation in the uroporphyrinogen III synthase gene. This mutation results in reduced enzyme levels in heme synthesis and the accumulation of pathogenic porphyrin isomers, uroporphyrin I and coproporphyrin I, leading to the clinical manifestations of CEP. Typically, CEP manifests shortly after birth with severe cutaneous photosensitivity, blistering, ulceration, and scarring. Erythrodontia, acro-osteolysis, and skeletal abnormalities are frequently present in conjunction with it. It can even manifest in utero as hydrops fetalis, with pink or red diaper staining as an early diagnostic clue. In this case, we present a 17-year-old male with complaints of discharge over the left foot, blisters upon sunlight exposure, extensive mottled pigmentation, excessive facial hair, mutilated fingers, and verrucous growth over the toes. Using a Wood's lamp revealed pink fluorescence of teeth and ulcers on the foot. Laboratory investigations demonstrated anemia, leukocytopenia, thrombocytopenia, and elevated urine uroporphyrin 1 and coproporphyrin 1 levels. Current treatment approaches include sun protection to avoid further skin damage, beta-carotene to reduce oxidative stress, and blood transfusions to manage anemia. Stem cell transplantation remains the sole curative therapy for this exceedingly rare condition. This case report underscores the rarity and complexity of CEP and emphasizes the challenges in its management.
PubMed: 38576642
DOI: 10.7759/cureus.55558 -
Scientific Reports Mar 2024To examine clinical course of early systemic sclerosis (SSc) and identify factors for progression of acro-osteolysis by a retrospective cohort study. Dual time-point...
To examine clinical course of early systemic sclerosis (SSc) and identify factors for progression of acro-osteolysis by a retrospective cohort study. Dual time-point hand radiography was performed at median interval (range 3.0 ± 0.4 years) in 64 recruited patients. Progressive acro-osteolysis was defined as the worsening of severity of acro-osteolysis according to rating scale (normal, mild, moderate, and severe). Incidence of the progression was determined. Cox regression was analyzed for the predictors. A total of 193.6 per 100 person-years, 19/64 patients had progressive acro-osteolysis with incidence of 9.8 per 100-person-years (95% CI 6.3-15.4). The median time of progressive acro-osteolysis was 3.5 years. Rate of progression increased from 1st to 3rd years follow-up with the progression rate at 1-, 2- and 3-years were 0, 2.0 and 18.3%, respectively. Patients with positive anti-topoisomerase I tended to have more progressive acro-osteolysis but no significant predictors on Cox regression. 44%, 18%, and 33% of who had no, mild, and moderate acro-osteolysis previously developed progression and 10 turned to be severe acro-osteolysis. In conclusion, the incidence of progressive acro-osteolysis was uncommon in early SSc but the rate of progression was pronouncedly increasing after three years follow-up. A half of the patients progressed to severe acro-osteolysis.
Topics: Humans; Retrospective Studies; Acro-Osteolysis; Scleroderma, Systemic; Radiography; Disease Progression
PubMed: 38429484
DOI: 10.1038/s41598-024-55877-x -
Pediatrics International : Official... 2024
Topics: Humans; Hajdu-Cheney Syndrome; Japan; Joint Diseases; Siblings
PubMed: 38409917
DOI: 10.1111/ped.15743 -
Current Rheumatology Reviews Jan 2024Primary hyperparathyroidism (PHPT) should be considered in the differential diagnosis of a patient with suspected secondary osteoporosis, and severe osteoporosis with...
BACKGROUND
Primary hyperparathyroidism (PHPT) should be considered in the differential diagnosis of a patient with suspected secondary osteoporosis, and severe osteoporosis with multiple fractures is frequently the first clinical manifestation of the disease.
CASE PRESENTATION
Mutilating arthritis (arthritis mutilans) can be part of the clinical presentation of a number of rheumatic diseases, most commonly seen in psoriatic arthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, but also in systemic lupus, systemic sclerosis, and multicentric reticulohistiocytosis. Evidence exists that subperiosteal and subchondral bone resorption, seen in PHPT, could induce the so-called 'osteogenic synovitis', which could eventually lead to the development of a secondary osteoarthritis with bone deformities.
CONCLUSION
Here, we present a case report of a patient initially diagnosed with PHPT who presented with mutilating arthritis of the finger joints and discuss whether the severe acro-osteolysis is a manifestation of the endocrinopathy or whether there is a co-existing undiagnosed inflammatory joint disease.
PubMed: 38314597
DOI: 10.2174/0115733971273126231214063403 -
Joint Bone Spine Feb 2024To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of...
OBJECTIVE
To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc.
METHODS
HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales.
RESULTS
Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66-99%) and 80% (95% CI: 59-93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47-90%) and 95% (95% CI: 76-99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1-3) versus 0 (IQR: 0-1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability.
CONCLUSION
HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.
PubMed: 38309517
DOI: 10.1016/j.jbspin.2024.105699 -
Orphanet Journal of Rare Diseases Dec 2023Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) is an autosomal dominant disease with increased bone reabsorption in the carpus and tarsus and the elbows, knees and... (Review)
Review
BACKGROUND
Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) is an autosomal dominant disease with increased bone reabsorption in the carpus and tarsus and the elbows, knees and spine. The disease is extremely heterogeneous and secondary and tertiary injuries vary widely and can lead to progressive disability and severe functional limitations. In addition to the available and upcoming drug therapies, physical medicine and rehabilitation are important treatment options. Currently, the indication and plan are overlooked, nonspecific and reported only for one patient.
METHODS
We describe a case series of MCTO patients diagnosed and followed by a centre to identify functional deficit as a potential clinical marker of disease progression for future etiological therapies. In addition, we define a symptomatic treatment approach and specific clinical management, including a patient-centred rehabilitation approach. Functional assessments are performed independently by a multidisciplinary group to establish the functional abilities of patients and the relationship between residual motor skills and their degree of autonomy and participation. We suggest a way to identify a rehabilitation plan based on a specific disease using the International Classification of Functioning, Disability and Health Children and Youth (ICF-CY).
RESULTS
To define a reliable and reproducible "Function Profile", through age and over time, we used to value the disease status according to the ICF-CY domains. It could be used to determine the complexity of the illness, its overall impact on the complexity of the person and the burden on the caregiver, and an eventual short- and long-term rehabilitation plan for MCTO and other ultra-rare diseases.
CONCLUSION
Based on the MCTO experience, we suggest a way to determine a rehabilitation plan based on a specific disease and patient needs, keeping in mind that often the final point is not recovering the full function but improving or maintaining the starting point. In all cases, each patient at the time of diagnosis requires a functional assessment that must be repeated over time to adjust the course of rehabilitation. The evaluations revealed the importance of early rehabilitation management in enhancing independence, participation and control of stress deconditioning, shrinking of muscle tendons and loss of movement to immobility.
Topics: Child; Adolescent; Humans; Osteolysis; Activities of Daily Living; Disease Progression; Hajdu-Cheney Syndrome
PubMed: 38124110
DOI: 10.1186/s13023-023-02976-z