A rare LMNA missense mutation causing a severe phenotype of mandibuloacral dysplasia type A: a case report / Uma rara mutação missense no gene LMNA causando um fenótipo grave de displasia mandibuloacral tipo A: relato de caso

ABSTRACT 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.

RESUMO Objetivo: Relatar o caso de uma jovem que apresentava um fenótipo grave de displasia mandibuloacral tipo A (MADA) caracterizado por alterações osteolíticas proeminentes e defeitos ectodérmicos, associados a uma rara mutação homozigótica missense no gene LMNA (c.1579C>T). Descrição do caso: Uma menina de seis anos foi avaliada durante hospitalização apresentando os seguintes sinais dismórficos: alopecia subtotal, fácies dismórfica com olhos proeminentes, micrognatia e retrognatia acentuada, nariz pequeno e adunco, dentes apinhados e lábios finos, lipodistrofia generalizada, ombros estreitos e inclinados, rigidez articular e reabsorção óssea nas falanges terminais. Ao exame dermatológico, observou-se pele atrófica, perda da elasticidade cutânea, hiperceratose, calcinose dérmica e manchas hiperpigmentadas e hipocrômicas. Exames radiológicos realizados mostraram ausência de côndilos mandibulares bilaterais, reabsorção da clavícula com massa óssea amorfa local confluindo com as escápulas, articulações do ombro com subluxação e displasia óssea severa, com displasia coxofemoral, osteopenia e calcificações subcutâneas. Comentários: MADA é uma doença autossômica recessiva rara causada por mutações no gene LMNA. Caracteriza-se por deformidades craniofaciais, anomalias esqueléticas, alterações cutâneas, lipodistrofia em determinadas regiões do corpo e envelhecimento precoce. MADA típica é causada pela mutação p.R527H no gene LMNA. No entanto, a análise molecular realizada com células epiteliais orais obtidas da paciente mostrou a mutação rara c.1579C>T, p. R527C no exon 9 do gene LMNA. Esta é a sexta família identificada com essa mutação descrita na literatura.

Acro-osteolysis in a Filipino male with Vinyl chloride exposure: A case report

@#Occupational acro-osteolysis pertains to bone resorption of the distal phalanges of the hands and feet among workers with vinyl chloride exposure. We report the case of a Filipino man with osteolysis of the distal phalanges of the hands initially considered to have systemic sclerosis. The patient had gradual shortening of the fingers, thickening of the skin over the extremities, and hypopigmented patches over a span of more than 20 years. His lower extremities presented with non-pitting edema, skin thickening, and neuropathy, without shortening of the digits. Difficulty of ambulation was apparent due to the development of feet inversion. Radiographic findings of the hands and feet included resorption of distal phalanges, erosive and sclerotic changes, and narrowed joint spaces. Other conditions considered were Hansen’s disease, skeletal tuberculosis, and diabetic neuropathic arthropathy, which were eventually ruled out. The final diagnosis was occupational acro-osteolysis secondary to vinyl chloride exposure. The patient underwent serial total contact casting of the bilateral lower extremities to relieve bipedal edema and to reposition the feet. This case emphasizes the significance of investigating a patient’s occupational history and highlights a rare sequela of exposure to a commonly used chemical agent in the manufacture of polyvinyl chloride products.

A Case of Acroosteolysis in Primary Hypertrophic Osteoarthropathy

Primary hypertrophic osteoarthropathy or pachydermoperiostosis is a rare hereditary disorder characterized by digital clubbing, pachydermia and periostosis. Its precise incidence and prevalence is still unknown due to the lack of controlled data. It occurs without any underlying causes and usually has a chronic course. Life expectancy may be of normal standards, but many patients develop multiple functional and cosmetic complications. So, it is important to diagnose this disease at an early stage and to treat the symptomat for the quality of life. We report a case of primary hypertrophic osteoarthropathy in a 68-year-old male with clinical features such as digital clubbing and pachydermia, radiographic findings of acroosteolysis and periosteal new bone formation.

Haim Munk syndrome: Report of two siblings of Northern India treated with acitretin.

Haim Munk Syndrome (HMS) is the allelic mutation of exon 6 codon in cathepsin C gene. Here, we present two cases of same family with HMS having all the cardinal features of HMS which includes palmo plantar keratoderma and periodontitis along with arachnodactyly, acroosteolysis, onychogryphosis, and marked osteopenia on hand wrist radiographs. Both the siblings were treated with cotrimoxazole, acetretin and topical keratolytics and followed up over a period of one year, showed remarkable improvement in palmo plantar keratoderma and periodontitis.

Pyknodysostosis: report of a rare case with review of literature

Pyknodysostosis is a rare autosomal recessive disorder characterized by the post natal onset of short limbs, short stature, and generalized hyperostosis along with acro-osteolysis with sclerosis of the terminal phalanges, a feature that is considered essentially pathognomonic. Other features include persistence of fontanelles, delayed closure of sutures, wormian bones, absence of frontal sinuses, and obtuse mandibular gonial angle with relative mandibular prognathism. We report a case of 17-year-old girl who presented with a chief complaint of retention of deciduous teeth. General physical examination demonstrated short stature, frontal and parietal bossing, depressed nasal bridge, beaked nose, hypoplastic midface, wrinkled skin over the finger tips, and nail abnormalities. Radiographs showed multiple impacted permanent and supernumerary teeth, hypoplastic paranasal sinuses with acro-osteolysis of terminal phalanges, and open fontanelles, and sutures along with wormian bones in the lambdoidal region.

A Case Report of Hajdu-Cheney Syndrome

Hajdu-Cheney syndrome (HCS) is a rare skeletal dysplasia that is characterized by acroosteolysis of the distal phalanges, distinctive craniofacial and skull changes, dental abnormalities and generalized osteoporosis. The clinical and radiologic characteristics are variable and these characteristics progress with age. This syndrome shows autosomal dominant inheritance with sporadic cases. The genetic defects or molecular pathogenesis of HCS are still unknown. We experienced a case of Hajdu-Cheney syndrome in a 20-year-old man who had generalized osteoporosis with multiple non-traumatic spine compression fractures. He had acroosteolysis of the hands and feet, wormian bones in the skull, facial dysmorphism (mid-facial flattening, micrognathia and bushy eyebrows), a high arched palate, malocclusion and short dental alveolar processes. HCS was diagnosed based on the clinical and radiologic evidence. For the differential diagnosis, we excluded the other possible causes of the acroosteolysis and wormian bones, including hyperparathyroidism, osteogenesis imperfecta, hypophosphatemia and mandibuloacral dysplasia. The specific treatment of HCS is unknown, but case reports with bisphosphonate treatment have been reported.

Acroosteolysis of Scleroderma Associated with a Felon / 대한정형외과학회잡지

The Scleroderma is a chronic inflammatory disease of the connective tissue with involvement of the skin and other organs. It can be a manifestation of various disorders and occasionally acroosteolysis in the phalanges. Acroosteolysis is characterized by bone resorption or destruction in the phalanges, while the base is preserved. The pathogenesis of acroosteolysis in patients with scleroderma is a blood-flow disorder that is mainly associated with an abnormal accumulation of collagen in all tissues, microangiopathy and infections in the phalanges. The phalanges in patients with scleroderma are prone to continuous infections as a felon or skin ulcers due to atrophy of the subcutaneous tissue, dry and sclerotic skin, or a disorder of the immune system. We experienced a patient who had acroosteolysis with scleroderma of the phalanges, and this was associated with a felon. We report on this case along with a brief review of the literature.

A case of acro-osteolysis caused by peripheral neuropathy after minor burn injury / 대한내과학회지

Acro-osteolysis is characterized by bone resorption in the fingers and toes and can occur in several diseases. Occupational exposure to polyvinyl chloride polymers, thermal injury, and repetitive mechanical injury can also cause acro-osteolysis. The pathophysiology of the disease is unknown, but a unifying theme of vascular and mechanical injury is presented. Signs include Raynaud's phenomenon, bone loss in the hand and cold sensitivity. We report the case of a 67-year-old woman who presented with acro-osteolysis after being burned repeatedly.

A case of acro-osteolysis caused by peripheral neuropathy after minor burn injury / 대한내과학회지

Acro-osteolysis is characterized by bone resorption in the fingers and toes and can occur in several diseases. Occupational exposure to polyvinyl chloride polymers, thermal injury, and repetitive mechanical injury can also cause acro-osteolysis. The pathophysiology of the disease is unknown, but a unifying theme of vascular and mechanical injury is presented. Signs include Raynaud's phenomenon, bone loss in the hand and cold sensitivity. We report the case of a 67-year-old woman who presented with acro-osteolysis after being burned repeatedly.

A Case of Hereditary Sensory Neuropathy Type II with Acroosteolysis / 대한류마티스학회지

The hereditary sensory neuropathy is a very rare disease characterized by prominent sensory loss without corresponding motor involvement, but may be associated with autonomic features. Currently, the disease is divided into five main types and most frequent are Type I and Type II. The type II hereditary sensory neuropathy is characterized by autosomal recessive inheritance, onset in utero or in infancy, loss of touch-pressure sense more than paintemperature sense, and almost total absence of myelinated nerve fibers. In this case, we describe a 23 years old female patient with acroosteolysis and heel ulcer who was diagnosed as hereditary sensory neuropathy type II.

A Case of Sjogren Syndrome Associated with Acroosteolysis / 대한류마티스학회지

Acroosteolysis (AOL) refers to a destructive process involving distal phalangeal shaft while the tuft and base are preserved. It can be a manifestation of various diseases, such as scleroderma, Raynaud's disease, rheumatoid vasculitis, psoriasis, renal osteodystrophy and leprosy. Occupational exposure to polyvinyl chloride polymers, thermal injury, and repetitive mechanical injury can also cause this problem. Although the exact pathogenesis of AOL is uncertain, a unifying theme of vascular and mechanical injury is presented. Recently, we experienced a 32-year-old woman complained of xerophthalmia, zerostomia and polyarthralgia which was diagnosed as Sj6gren syndrome associated with acroosteolysis. After administration of prednisolone, cyclophosphamide and oral bromhexine, subsidence of her symptoms was observed. We report this case with a review of relevant literature.