Congenital insensitivity to pain is a rare human condition in which affected individuals do not experience pain throughout their lives. This study aimed to identify the molecular etiology of congenital insensitivity to pain in two Thai patients. Clinical, radiographic, histopathologic, immunohistochemical, and molecular studies were performed. Patients were found to have congenital insensitivity to pain, self-mutilation, acro-osteolysis, cornea scars, reduced temperature sensation, tooth agenesis, root maldevelopment, and underdeveloped maxilla and mandible. The skin biopsies revealed fewer axons, decreased vimentin expression, and absent neurofilament expression, indicating lack of dermal nerves. Whole exome and Sanger sequencing identified a rare homozygous variant c.4039C>T; p.Arg1347Cys in the plakin domain of Plec, a cytolinker protein. This p.Arg1347Cys variant is in the spectrin repeat 9 region of the plakin domain, a region not previously found to harbor pathogenic missense variants in other plectinopathies. The substitution with a cysteine is expected to decrease the stability of the spectrin repeat 9 unit of the plakin domain. Whole mount in situ hybridization and an immunohistochemical study suggested that Plec is important for the development of maxilla and mandible, cornea, and distal phalanges. Additionally, the presence of dental anomalies in these patients further supports the potential involvement of Plec in tooth development. This is the first report showing the association between the Plec variant and congenital insensitivity to pain in humans.

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).
METHODS: 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.
CONCLUSIONS: 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.

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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.

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.
METHODS: 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.
CONCLUSIONS: 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.

BACKGROUND: Osteoarthritis of the hand joints in systemic sclerosis (SSc) patients might be an independent manifestation leading to limitation of upper extremity function. There is no publication quantitatively assessing the thickness of articular cartilage within the hand joints of SSc patients by MRI. The purpose of our study was to quantify the condition and thickness of hand joints cartilage with three-dimensional quantitative MRI (3D q-MRI).
METHODS: The study was conducted in twenty people: ten patients with SSc and ten healthy individuals. All participants were examined with the 3D q-MRI with 3T scanner. The cartilage thickness of proximal (PIP) and distal interphalangeal (DIP) joints as well as metacarpophalangeal joints was measured.
RESULTS: There was no significant difference in cartilage thickness between both groups. However, the joint cartilage was thinner in fingers with acro-osteolysis. In PIP joint of the fingers with acro-osteolysis, the mean cartilage thickness was 0.5 mm (p = 0.0043) and 0.4 mm (p = 0.0034) in DIP joints.
CONCLUSIONS: Quantitative MRI analysis of the joints of the hands of SSc patients does not indicate changes in thickness of the articular cartilage. A significant reduction in the articular cartilage thickness of the fingers with acro-osteolysis indicates the potential of an ischemic basis of articular cartilage destruction in SSc patients.

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Hajdu-Cheney syndrome or acro-dento-osteo-dysplasia syndrome is a rare disease characterized by band osteolysis of distal phalanges and facial dysmorphia, among other manifestations. We present the case of a 45-year-old male who consulted for mechanical joint pain of both hands, facial dysmorphism, cranio-facial alterations, and digital telescoping with acroosteolysis.

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