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.

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.

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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Frank-Ter Haar syndrome (FTHS), Winchester syndrome (WS), Torg syndrome (TS) and Multicentric Osteolysis Nodulosis and Arthropathy (MONA) are progressive skeletal dysplasia consisting of acro-osteolysis. Mutation in Matrix Metalloproteinase 2 (MMP2), Matrix Metalloproteinase 14 (MMP14) and SH3PXD2B are known genetic defects in these disorders. We hereby report a 5 years and 9 months old girl suffering from progressive limb deformity. She is the first child of a relative couple, who was referred to metabolic disorders\' clinic due to poor growth and bone pain. On physical examination, minor facial dysmorphism, hypertrichosis, severe hand deformity with limitation in range of motion in carpal, metacarpal and phalangeal joints, hallux valgus deformity of feet, soft tissue hypertrophy and nodule formation in palmoplantar areas were detected. Her past history indicated a cardiac defect resulting in open heart surgery at 8 months of age. Genetic study revealed a new homozygote nonsense mutation in MMP2 gene explaining her clinical manifestations. We recommend careful evaluation and follow-up of patients with congenital heart disease, as it may be the first presentation of a genetic multisystem disorder. Early differentiation of the disease from other skeletal dysplasia and rheumatologic disorders could prevent unnecessary management.

UNASSIGNED: To perform molecular genetic analysis of a patient diagnosed with primary hypertrophic osteoarthropathy (PHO) with malnourishment, intussusception, and acro-osteolysis.
UNASSIGNED: At the age of 7 years, a boy born to a consanguineous couple was diagnosed with PHO attributed to delayed closure of the cranial suture, eczema, clubbing of fingers, and swelling of the knee and ankle. Clinical characteristics and follow-up data for 3 years were collected and analyzed. Trio whole-exome sequencing (WES) and copy number variant sequencing were used to screen for causative genetic variants. Candidate variants of the patient and his parents were confirmed by Sanger sequencing. When he was 7 years old, trio WES found that he had biallelic novel variants c.498 + 1G > A, inherited from his parents, in the HPGD gene. The patient was markedly malnourished. Ultrasonography and computed tomography showed intussusception with a gradual expansion of the duodenum, localized intestinal wall thickening, and acro-osteolysis. Cross-sectional blood tests showed that the patient had continuously decreased levels of serum 25-hydroxy vitamin D and serum ferritin at the age of 7and 10 years.
UNASSIGNED: PHO due to HPGD defects is rare in pediatric patients, and finding homozygous novel c.498 + 1G > A has expanded the spectrum of causative variants of HPGD and provided a clue for genotype-phenotype correlation analysis. Similar to mouse model results, human HPGD deficiency may also cause abnormal digestive tract development, and related secondary vitamin D deficiency and acro-osteolysis should be considered in HPGD-related PHO.

Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog protein 2 gene (NOTCH2). Treatment of this rare disease is challenging because there are no established guidelines worldwide. Previous case reports using bisphosphonates, denosumab, or teriparatide suggested that curative treatment for HCS did not exist yet in terms of preventing the disease progression. Therefore, the efficacy of romosozumab for osteoporosis in patients with HCS needs to be evaluated. Herein, we report the case of a 43-year-old woman who had progressive acro-osteolysis and repeated fractures since the age of 29 years. Next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G>A, leading to Trp2253Ter replacement in NOTCH2. Romosozumab treatment was initiated because she had already received bisphosphonate for more than 10 years at other hospitals. After 1 year of romosozumab treatment, the bone mineral density (BMD) increased by 10.2%, 6.3%, and 1.3%, with Z scores of -2.9, -1.6, and -1.2 at the lumbar spine, femoral neck, and total hip, respectively. In addition, C-telopeptide was suppressed by 26.4% (0.121 to 0.089 ng/mL), and procollagen type I N-terminal propeptide increased by 18.7% (25.2 to 29.9 ng/mL). This was the first report of romosozumab treatment in patient with osteoporosis and HCS in Korea. One year of romosozumab treatment provided substantial gains in BMD with maintaining the last acro-osteolytic status without deteriorating, representing a possible treatment option for HCS.

BACKGROUND: Acro-osteolysis (AO) refers to resorption of the distal finger and toe phalanges. It displays two patterns: (i) diffuse AO and (ii) transverse or bandlike AO. AO can be a sign of local distress (e.g. of toxic origin), but is very often a sign of a constitutional or systemic acquired disorder.
METHODS: A 15-year-old girl was referred to a paediatric rheumatologist for recurrent pain in her fingertips. She presented a particular cross-sectional AO associated with the presence of intraosseous cysts and bone fragility with atypical fractures. Initial laboratory tests and radiological examination did not allow an etiological diagnosis. Genetic studies revealed a 12p11.22-p11.23 microduplication of 900 kb including the PTHLH (parathyroid hormone-like hormone) gene, which encodes for a hormone involved in the regulation of endochondral ossification and differentiation of chondrocytes, via its PTHLH receptor.
CONCLUSIONS: To date, 12p11.22-p11.23 duplications have been reported in five families with skeletal abnormalities, and in particular AO and enchondromatosis associated with bone fragility. This new observation, added to the other reported cases, suggests a close relationship between the presence of this microduplication and the skeletal abnormalities found in the patient. We suggest the descriptive name ABES (acro-osteolysis, bone fragility and enchondromatosis syndrome) to designate this disorder.

Systemic sclerosis is an autoimmune chronic sclerotic disease that can damage organs and cause serious complications for the patient such as musculoskeletal manifestations, Gastrointestinal involvement, pulmonary involvement, and renal disease. Acro-osteolysis is one of the musculoskeletal manifestations that causes corrosion of the bones in the fingertips of the hand and feet. In this paper, we have reported the rarely current evidence of severe Acro-osteolysis of the distal phalanges of the hands by radiological x-ray.

Hajdu-Cheney syndrome (HCS) is a very rare autosomal-dominant congenital disease associated with mutations in the NOTCH2 gene. This disorder affects the connective tissue and is characterized by severe bone resorption. Hajdu-Cheney syndrome most frequently affects the head and feet bones (acroosteolysis).
We present an extremely rare case of a 34-year-old male with Hajdu-Cheney syndrome. The patient was admitted to the Department of Oral Surgery, Medical University of Gdańsk, in order to perform the extraction of three teeth. These teeth were not eligible for conservative treatment and prosthetic reconstruction. The patient was treated with denosumab (angiogenesis and receptor activator of nuclear factor-κB RANK ligand inhibitor, RANKL).
Denosumab is a monoclonal antibody against RANKL. This drug works through a suppression of osteoclast activity. In cases of patients in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated, denosumab has been approved for the treatment off-label. In patients receiving denosumab, a delayed wound healing in the oral cavity and osteonecrosis may occur. Dental procedures involving the alveolar bone process (tooth extractions and bone alveoloplasty) may be a risk factor for medication-related osteonecrosis of the jaw (MRONJ). Spontaneous osteonecrosis is rarely observed. MRONJ consists of the destruction of exposed bone, with the exposure persisting for a minimum of 6-8 weeks. This is the first article about an HCS patient treated with denosumab who underwent invasive oral surgery procedures. This case report highlights the difficulties for professionals occurring during the oral surgery procedures in such patients.