Pathological mandibular fracture complicated by osteonecrosis in an adult patient with pycnodysostosis: clinical report and review of the literature.

Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia, and increased caries) are also frequent; due to bone metabolism alteration, the patients have an increased risk for jaw osteomyelitis, especially after tooth extraction or mandible fracture. Other complications are obstructive sleep apnea, endocrine alterations and cytopenia. Pycnodysostosis is caused by biallelic loss of function variants in CTSK gene, coding the lysosomal protease cathepsin K. CTSK is involved in the degradation of bone matrix proteins, such as type I and type II collagen. In pycnodysostosis, this degradation is decreased, leading to increased bone density and bone fragility with pathological fractures and poor healing. We present a clinical report of a female adult patient with typical pycnodysostosis phenotype. At the age of 52 years, she had a pathological spontaneous fracture of the right mandible complicated by osteonecrosis, treated with load bearing osteosynthesis. The direct sequencing of CTSK gene revealed the presence of the pathogenic homozygous variant c.746T>A, (p.Ile249Asn), that confirmed the diagnosis of pycnodysostosis. We also review the literature case series published to date, that suggest to always consider the diagnosis of pycnodysostosis in case of osteosclerosis, even in the absence of brachydactyly or short stature. This report details the natural history of the disease in this patient, from childhood to adulthood, and highlights the importance of a quality of life assessment. In addition, we describe a case of mandibular osteonecrosis and spontaneous fracture in pycnodysostosis, drawing attention on the maxillofacial complications in these patients and on the importance of a personalized follow-up.

Surgical treatment of pycnodysostosis associated with pathological tibial fracture : Case report and review of the literature.

BACKGROUND: Pycnodysostosis is a rare autosomal recessive lysosomal disorder of bone characterized by diffuse skeletal condensation with thickening of the cortex and narrowing of the medullary canal. CASE PRESENTATION: We present the case of a 4-year-old girl diagnosed with pycnodysostosis and associated pathological tibial fracture. The tibia had an absence of medullary canal. Surgery included reduction and reaming of the canal with placement of a 5 mm diameter telescopic growing nail. CONCLUSION: The presentation of pycnodysostosis as tibial fracture is rare and there is limited literature on its management. We showed its approach focusing mainly on the management of the absent medullary canal.

A Case Report of Pycnodysostosis Associated with Multiple Pituitary Hormone Deficiencies and Response to Treatment

Pycnodysostosis is a rare autosomal recessive osteosclerotic bone disorder associated with short stature and multiple bony abnormalities. Growth hormone (GH) deficiency may contribute to short stature in about 50% of patients. Available literature has rarely reported other pituitary hormone deficiencies in pyknodysostosis. Though the management remains conservative, recombinant human GH (rhGH) has been tried in selected patients. Here we present a case of pycnodysostosis which was evaluated for associated co-morbidities and found to have multiple pituitary hormone deficiencies. A 7-year-old girl was referred to our centre for evaluation of short stature. On examination, she had frontal and occipital bossing, limited mouth opening, hyperdontia with multiple carries, short and stubby digits and short stature. Investigation revealed dense sclerotic bones with frontal and occipital bossing, non-fusion of sutures with obtuse mandibular angle, non-pneumatised sinuses, small 'J' shaped sella turcica, acro-osteolysis of digits and absent medullary cavities. Cathepsin-K gene mutation analysis confirmed the diagnosis of pycnodysostosis. She was screened for associated co-morbidities and was found to have concomitant GH deficiency. Treatment with rhGH brought about an increase of 1 standard deviation score in height over 2 years and also unmasked central hypothyroidism at three months necessitating thyroxine replacement.

Sleep-disordered breathing in children with pycnodysostosis.

Upper airway obstruction is a common feature in pycnodysostosis and may cause obstructive sleep apnea (OSA). The aim of our study was to analyze sleep-disordered breathing and respiratory management in children with pycnodysostosis. A retrospective review of the clinical charts and sleep studies of 10 consecutive children (three girls and seven boys) with pycnodysostosis seen over a time period of 10 years was performed. Six patients had severe OSA and/or nocturnal hypoventilation and were started on continuous positive airway pressure (CPAP) as a first treatment at a median age of 3.4 ± 2.6 years, because of the lack of indication of any surgical treatment. Three patients could be weaned after several years from CPAP after spontaneous improvement (two patients) or multiple upper airway surgeries (one patient). Three patients had upper airway surgery prior to their first sleep study with two patients still needing CPAP during their follow-up. Only one patient never developed OSA. Patients with pycnodysostosis are at a high risk of severe OSA, underlying the importance of a systematic screening for sleep-disordered breathing. Multidisciplinary care is mandatory because of the multilevel airway obstruction. CPAP is very effective and well accepted for treating OSA.

Multisuture Craniosynostosis and Papilledema in Pycnodysostosis: A Paradox?

Pycnodysostosis (PYCD) is a rare autosomal-recessive skeletal disorder that typically presents with osteosclerosis of the majority of the postcranial skeleton and osteolysis of the calvarium, manifesting as persistent open cranial fontanelles and widely spaced cranial sutures. Craniosynsostosis in PYCD is a somewhat paradoxical feature, and has only been rarely reported. The authors present a unique case of a 6-year-old girl with PYCD, multisuture craniosynostosis involving the coronal and sagittal sutures, severe obstructive sleep apnoea, and raised intracranial pressure presenting as papilledema. She underwent a frontofacial monobloc distraction advancement which successfully corrected her papilledema and obstructive sleep apnoea.Pycnodysostosis is caused by a loss of function mutation in the CTSK gene that codes for the lysosomal cysteine protease, cathepsin K (CTSK). Loss of CTSK impairs the ability of osteoclasts to degrade bone extracellular matrix. Differences in osteoclast phenotype and extracellular matrix composition between membranous and cartilaginous bone may explain the clinical features of PYCD. Animal model studies suggest that craniosynostosis may arise due to variations in patient genetic background.

Picnodisostosis familiar, reporte de un caso tras 10 años de seguimiento / Family picnodisostosis, report of a case after 10 years of follow-up

Resumen: Introducción: La picnodisostosis es una rara enfermedad secundaria en una mutación en el gen 1q21 que codifica la catepsina K, enzima implicada en el metabolismo de osteonectina, osteopontina y colágeno I. La incidencia mundial es de 1-1.7 casos por millón, sin prevalencia por género, se caracteriza clínicamente por talla baja, deformidades craneales, «cara de pájaro¼ y fragilidad ósea con tendencia a fracturas patológicas, que afectan predominantemente los huesos largos y ocasionalmente en los pedículos vertebrales. Radiológicamente es característica la presencia de osteoesclerosis con canales medulares permeables. Aunque existen numerosos reportes de casos clínicos en la literatura, pocos son los que describen familias con más de un individuo afectado y el seguimiento suele ser a corto plazo. Objetivo: Analizar la evolución clínica de los pacientes afectados. Material y métodos: Se realizó estudio retrospectivo, descriptivo, observacional de tres pacientes con diagnóstico de picnodisostosis, en el período de Julio 2006 a Marzo de 2016. Resultados: Se observaron diferentes formas de afectación de la picnodisostosis, algunas de ellas atípicas como la espondilólisis y una fractura de escápula en una paciente. Conclusiones: El presente estudio podría ser el análisis longitudinal más extenso del que se tenga registro. Conocer la variedad de manifestaciones y complicaciones presentadas permitirá al lector seleccionar el mejor método de tratamiento para cada caso.

Abstract: Introduction: Pycnodysostosis is a rare disease secondary to a mutation in gen 1q21 that codifies the cathepsin K, proteolitic enzyme implicated in the metabolism of osteonectin, osteopontin and type I colagen. Its global incidence is around 1-1.7 cases per million, without genre prevalences, it is clinically caracterized by short stature, craneal deformities, «bird's face¼ and bone fragility with pathological fractures tendency predominantly affecting long bones and occasionally vertebral pedicles. Radiologically is characterized by sclerous bones with permeable medular cannel. Despite there are numerous clinical reports on medical literature, just a litlle describe families with more than one afected member and its followship is usually short-term. Objective: To analize clinical evolution of these afected patients. Material and methods: A retrospective, descriptive, observational study was reelized in three patients with diagnosis of pycnodisostosis, between July 2006 and March 2016. Results: different affection forms of pycnodisostosis where observed, some of them, atipical, as for example spondilolisis and a escapule fracture in one patien. Conclusions: The present study could be the longest longitudinal report ever registered. By knowing the presented variety of manifestations and complications, the reader could select the best treatment method for each case.

An Update on Osteomyelitis Treatment in a Pycnodysostosis Patient.

PURPOSE: The aims of the present study were to discuss the demographic distribution and clinical characteristics of patients with pycnodysostosis (PYCD) and the onset of osteomyelitis and its treatment using a literature review. The authors also report on an update of treatment of mandibular osteomyelitis in a patient with PYCD using a buccal fat pad (BFP) as a free graft. PATIENTS AND METHODS: The study was carried out in 2 steps. In the first step, an electronic search was undertaken in PubMed in March 2018, with 17 articles being included. In the second step, the authors present a case of mandibular osteomyelitis in a 30-year-old woman with PYCD treated by sequestrectomy and a BFP as a free graft (follow-up, 24 months). RESULTS: Twenty-one cases of osteomyelitis of the jaws in patients with PYCD were included. Dental extraction, mandibular fracture, and 1 case of facial trauma represented the causes of mandibular osteomyelitis. Treatments included resection associated with antibiotics and sequestrectomy alone or associated with antibiotics. CONCLUSIONS: Despite the good results of the present case, further studies using the BFP as an adjuvant for jaw osteomyelitis are necessary to elucidate its clinical efficiency and safety.

Traumatic cervical spine injuries in a patient with pycnodysostosis.

Pycnodysostosis is a rare hereditary disease, characterized by systemic bone sclerosis. Susceptibility to long bone fractures is characteristic, whereas vertebral fractures are extremely rare. We report a case of a 21-year-old man with a past history of pycnodysostosis and spontaneous leg fractures who was admitted in hospital for a neck pain after a banal fall. Radiological examination revealed C1-C2-C3 posterior arch fractures with a C3-C4 left articular fracture dislocation. A surgical stabilization was decided but refused by the patient. To the best of our knowledge, this is the first publication that reports pycnodysostosis with cervical spine traumatic staged injuries.

Pycnodysostosis at otorhinolaryngology.

AIM: Pycnodysostosis is a rare autosomal, recessive, skeletal dysplasia caused by a mutation in the cathepsin k gene. Pycnodysostosis is characterized by short stature, characteristic facial appearance (delayed closure of fontanelles and cranial sutures, mandibular hypoplasia and angle disorder, blue sclera), and acroosteolysis of the distal phalanges. Our aim was to describe the otorhinolaryngologic findings, differential diagnoses, various treatment options, and followup in eight cases of pycnodysostosis. METHOD: This retrospective clinical study used data from eight patients diagnosed with pycnodysostosis by a single pediatric endocrinologist primarily based on clinical and radiographic findings. All patients were referred to the otorhinolaryngology outpatient clinic by the pediatric endocrinology unit of the Marmara University between February 2013 and March 2015. Detailed medical histories were obtained in all cases and otorhinolaryngologic physical examination, blood assays, electrocardiogram, lateral skull X-rays, chest radiograph, cephalometric investigations, tympanograms, and audiograms were also carried out. Sleep videos of patients were recorded and those with upper airway problems were evaluated for sleep apnea by polysomnography. Informed consent form was obtained from the parents of all patients. RESULTS: Eight patients (7 females and 1 male) displaying proportionate dwarfism were included in the study. They had a mean age of 14.7 years (range: 13-16 y), the mean height of 141.3 cm (range 132-155 cm), and mean weight of 44.4 kg (range: 39.6-49.3 kg). All patients had facial dysmorphism with frontal bossing and the hands and feet had short digits with overlying cutaneous wrinkles that tapered off with large overriding nails. Midfacial hypoplasia and malocclusion were observed in seven of the eight patients (87.5%), four (50%) had micrognathia, and five (62.5%) had proptosis. Tympanograms and audiograms of all patients were type A and normal, and the mean of the pure tone audiogram was 13.3 dB (range: 10-16 dB). All patients had a narrow and grooved palate with disturbed dentition; two of them (25%) had mild markedness of the tongue base, five (62.5%) had grade 3 and three (37.5%) had grade 2 tonsillar hypertrophy, and five (62.5%) had adenoid hypertrophy. One patient (12.5%) had grade 3 Mallampati, four (50%) showed grade 2 Mallampati while three (37.5%) patients displayed grade 1 Mallampati score. Further, while six (75%) patients had no uvular pathology, one (12.5%) patient presented with uvular elongation and another patient had a bifid uvula. Cephalometric measurements such as PAS-UP (mean 5.67 mm; range: 5.0-7.6 mm) and PAS-TP (mean 9.61 mm; range: 8.5-12.2 mm) were lower than that of normal subjects. Video recordings showed that six of the eight patients (75%) had respiratory distress and four (50%) had sleep apnea. Polysomnography in these patients with sleep apnea showed that two had mild OSA (AHI: 18.2 and 20.1 events/hour) and two had severe OSA (AHI: 53.4 and 62.8 events/hour). For upper airway problems, an adenotonsillectomy was performed in two (25%) patients while two others required an adenoidectomy. Positive pressure ventilation was recommended in two patients with persistent sleep apnea after adeno/adenotonsillectomy. However, because of the parental objections, the follow-up polysomnographs could not be obtained. CONCLUSION: Pycnodysostosis is a very rare form of bone dysplasia. Otorhinolaryngologically, proper follow-up of these patients and appropriate treatment of upper airway problems are important to achieve an acceptable quality of life. Adeno/adenotonsillectomy and positive pressure ventilation, used as conservative approaches in treating upper airway problems, are effective and could be used instead of an aggressive surgery such as tracheotomy or maxillomandibular advancement. This study, to the best of our knowledge, is the largest ENT case series on pycnodysostosis.

Pycnodysostosis with novel gene mutation and sporadic medullary thyroid carcinoma: A case report.

RATIONALE: Pycnodysostosis is a rare autosomal recessive skeletal dysplasia caused by a mutation in the cathepsin K encoded by cathepsin K gene (CTSK). Medullary thyroid carcinoma (MTC) is also a relatively rare type of primary thyroid carcinoma. PATIENT CONCERNS: A 31-year-old woman presenting a short stature and a palpable nodule in the front of her neck that had gradually increased in size during the last 2 years was referred to our department. She has experienced multiple fractures at lower limbs in the last 2 decades. DIAGNOSES: The patient's clinical examination revealed short stature, underweight, a prominent forehead, stubby fingers, and a fixed nodule in the right thyroid lobe. Intraoral examination revealed multiple clinically malposed and missing teeth, as well as chronic periodontitis with a narrow and grooved palate. Radiographic examination revealed typical widely separated cranial sutures and an open anterior/posterior fontanel with an obtuse gonial angle, acroosteolysis, and osteosclerosis with narrowed medullary cavities. Ultrasonography of the thyroid gland showed a marked hypoechoic solid nodule in the right lobe in which tumor cell clusters were confirmed by ultrasound-guided fine needle aspiration biopsy and was suspected to be MTC. Laboratory tests revealed dramatically elevated serum calcitonin >2000 pg/L (reference range: 0-5 pg/L) and carcinoembryonic antigen (CEA) 134.37 ng/mL (reference range: 0-5 ng/mL). Genotypic screening revealed compound heterozygous mutations in the CTSK gene (c.158delA, P.Asn53Thr/c.C830T, P.Ala277Val) but no mutation associated with the familial forms of MTC. INTERVENTIONS: The patient underwent a total thyroidectomy with right-sided functional neck dissection. OUTCOMES: CEA and serum calcitonin decreased significantly postthyroidectomy, and no further fracture has been reported by the patient so far. LESSONS: The present study is the first to report a rare case of the coexistence of pycnodysostosis with a compound CTSK gene mutation and sporadic MTC. Radiological techniques and gene analysis play key roles in the definitive diagnosis.

Manejo de fractura en hueso patológico en la infancia: picnodisostosis / Management of fractures in pathological bone in childhood: pycnodysostosis

La picnodisostosis es una enfermedad poco común que pertenece a las displasias esqueléticas que presentan fragilidad ósea y fracturas frecuentes. Radiológicamente se caracteriza por incremento de la densidad y fragilidad óseas. OBJETIVO: Presentar el caso de un escolar con displasia esquelética con fracturas en hueso patológico y manejo quirúrgico. CASO CLÍNICO: Escolar de sexo femenino, con antecedente de picnodisostosis detectado en etapa preescolar. Consulta posterior a caída de bicicleta con fractura de ambos fémures que se manejan quirúrgicamente con placa de compresión bloqueada.

Pycnodysostosis is a rare condition within skeletal dysplasias presenting with brittle bones and frequent fractures. Radiologically, it is characterised by increased bone density and fragility. OBJECTIVE: To present the case of a primary schoolchild with skeletal dysplasia with pathological bone fractures and their surgical management. CASE REPORT: A female primary schoolchild with a history of pycnodysostosis detected during the pre-school period. She was seen after bicycle fall that resulted in the fracture of both femurs, that were surgically managed with a locking compression plate.

Fracturas múltiples de huesos largos en una escolar portadora de picnodisostosis: Reporte de caso / Multiple long bone fractures in a child with pycnodysostosis: A case report

Las fracturas en edad pediátrica son una entidad importante para considerar. Hay enfermedades en que los huesos del niño se fracturan ante traumatismos de menor energía. La picnodisostosis es un tipo inusual de displasia cráneo-metafisaria autosómica recesiva, cuya primera manifestación clínica suele ser una fractura en hueso patológico. Se presenta a una paciente, caucásica, de 9 años de edad, con diagnóstico de picnodisostosis, que ingresó al hospital por fractura del fémur derecho, por un mecanismo de baja energía. Los estudios radiográficos mostraron fracturas del fémur bilateral, fractura proximal de la tibia izquierda y consolidación viciosa en antecurvatum. Esta rara enfermedad se diagnostica a edades tempranas por talla baja, por fracturas repetidas o por traumas de baja energía. Las opciones terapéuticas son limitadas, y no se ha desarrollado una cura definitiva. Es importante, ante un paciente pediátrico con rasgos dismórficos faciales y fracturas en hueso patológico, sospechar displasias óseas, tales como la picnodisostosis y sus diagnósticos diferenciales.

Fractures are an important entity to consider in pediatric patients. There are certain diseases in which bones fracture with a minimal trauma. Pycnodysostosis is an autosomal recessive unusual type of cráneo metaphyseal dysplasia, that presents frequently as fracture in a pathological bone. A 9 year old caucasian female, diagnosed with pycnodysostosis, was admitted with a right femur fracture as a result of a low energy trauma. Radiographic studies showed bilateral femur fractures, proximal fracture and non-union in antecurvatum of the left tibia. Pycnodysostosis is a rare disease, generally diagnosed at an early age by growth restriction, frequent fractures or fractures with low energy trauma. Therapy alternatives are limited, and no permanent cure has been developed. If a patient has dysmorphic facial features and fractures in a pathological bone, it is important to suspect bone dysplasia, such as pycnodysostosis and its differential diagnoses.

[Multiple long bone fractures in a child with pycnodysostosis. A case report]. / Fracturas múltiples de huesos largos en una escolar portadora de picnodisostosis. Reporte de caso.

Fractures are an important entity to consider in pediatric patients. There are certain diseases in which bones fracture with a minimal trauma. Pycnodysostosis is an autosomal recessive unusual type of cráneo metaphyseal dysplasia, that presents frequently as fracture in a pathological bone. A 9 year old caucasian female, diagnosed with pycnodysostosis, was admitted with a right femur fracture as a result of a low energy trauma. Radiographic studies showed bilateral femur fractures, proximal fracture and non-union in antecurvatum of the left tibia. Pycnodysostosis is a rare disease, generally diagnosed at an early age by growth restriction, frequent fractures or fractures with low energy trauma. Therapy alternatives are limited, and no permanent cure has been developed. If a patient has dysmorphic facial features and fractures in a pathological bone, it is important to suspect bone dysplasia, such as pycnodysostosis and its differential diagnoses.

Las fracturas en edad pediátrica son una entidad importante para considerar. Hay enfermedades en que los huesos del niño se fracturan ante traumatismos de menor energía. La picnodisostosis es un tipo inusual de displasia cráneo-metafisaria autosómica recesiva, cuya primera manifestación clínica suele ser una fractura en hueso patológico. Se presenta a una paciente, caucásica, de 9 años de edad, con diagnóstico de picnodisostosis, que ingresó al hospital por fractura del fémur derecho, por un mecanismo de baja energía. Los estudios radiográficos mostraron fracturas del fémur bilateral, fractura proximal de la tibia izquierda y consolidación viciosa en antecurvatum. Esta rara enfermedad se diagnostica a edades tempranas por talla baja, por fracturas repetidas o por traumas de baja energía. Las opciones terapéuticas son limitadas, y no se ha desarrollado una cura definitiva. Es importante, ante un paciente pediátrico con rasgos dismórficos faciales y fracturas en hueso patológico, sospechar displasias óseas, tales como la picnodisostosis y sus diagnósticos diferenciales.

Pycnodysostosis presenting as atypical stridor.

OBJECTIVES: Pycnodysostosis is a rare genetic disorder caused by a mutation of the cathepsin K gene involved in bone turnover. It is responsible, in particular, for a combination of dwarfism and bone fragility. Upper airway obstruction may be observed, but associated stridor has never been previously described. MATERIALS AND METHODS: Single-centre retrospective study over a period of 15 years with review of the literature. RESULTS: Three children (aged 2-18 months) were managed for stridor and obstructive sleep apnoea syndrome confirmed by polysomnography. Physical examination of these children revealed stridor with laryngomalacia, characteristic dysmorphic features and failure to thrive. Patient 1 presented typical laryngomalacia treated by surgical section of the aryepiglottic folds. Patient 2 presented upper airway obstruction with a narrow nasopharynx and long soft palate, treated by surgery and noninvasive ventilation. Patient 3 presented moderate laryngomalacia and nasal obstruction, treated by surgery and noninvasive ventilation. CONCLUSION: The diagnosis of pycnodysostosis must be considered in the presence of atypical laryngomalacia associated with multifactorial upper airway obstruction, failure to thrive and dysmorphic syndrome. A genetics consultation is essential in these patients.

The role of cathepsin K in oral and maxillofacial disorders.

Cathepsin K (CTSK) was thought to be a collagenase, specifically expressed by osteoclasts, and played an important role in bone resorption. However, more and more research found that CTSK was expressed in more extensive cells, tissues, and organs. It may not only participate in regulating human physiological activity, but also be closely related to a variety of disease. In this review, we highlight the relationship between CTSK and oral and maxillofacial disorders on the following three aspects: oral and maxillofacial abnormities in patients with pycnodysostosis caused by CTSK mutations, oral and maxillofacial abnormities in Ctsk(-/-) mice, and the role of CTSK in oral and maxillofacial diseases, including periodontitis, peri-implantitis, tooth movement, oral and maxillofacial tumor, root resorption, and periapical disease.

Atypical femur fractures in a patient with pycnodysostosis: a case report.

Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail.

A Mutation in CTSK Gene in an Autosomal Recessive Pycnodysostosis Family of Chinese Origin.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon-intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient's CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis.

Picnodisostosis y fractura femoral: reporte y seguimiento a 2 años / Pycnodysostosis and femoral fracture: report and two-year follow-up

La Picnodisostosis consiste en un raro trastorno genético caracterizado por esclerosis ósea sistémica, cuya fisiopatología se debe a una deficiencia catepsina K, enzima esencial en la remodelación ósea. El problema ortópedico más importante en esta condición son las fracturas recurrentes de los huesos largos. Clínicamente se presenta con osteoesclerosis, talla baja, acroosteolisis de falanges distales, displasias ungueales, displasia clavicular, deformidades craneales secundarias al retardo en el cierre de suturas y fontanelas; miembros cortos, micrognatia, maxilar superior obtuso e inferior aplanado, retraso en la aparición de los dientes; y fragilidad ósea con tendencia a las fracturas. Se presenta caso de mujer de 27 años con Picnodisostosis, en control en Servicio de Traumatología Adulto Hospital Gustavo Fricke. Damos a conocer su historia clínica, desde el diagnóstico de su enfermedad, hasta las complicaciones y tratamientos ortopédicos y quirúrgicos de sus fracturas recurrentes...

Pycnodysostosis is an uncommon genetic malformation characterized by systemic bone sclerosis, whose pathophysiologyis due to essential enzyme deficiency in bone remolding, cathepsin K. The most relevant orthopedic problems of this condition are the recurrent long-bones fractures. A clinical case is presented: 27 year old, female patient controlling at the Adult Traumatology Service in Hospital Gustavo Fricke. We present her clinical story from diagnose to the fracture’s complications and treatments, orthopedic and surgical...

Upper airway surgery of obstructive sleep apnea in pycnodysostosis: case report and literature review.

Pycnodysostosis is an autosomal recessive disorder due to a mutation in the cathepsin K gene, which causes a decrease of the bone turnover; a review of the literature suggests that pycnodysostosis is frequently associated with severe respiratory obstruction, which needs surgical treatment. The aim of this paper is to describe the surgical treatment of a 3½-year-old girl affected by Pycnodysostosis complicated by a severe sleep-related respiratory disorder. The surgical treatment, consisting of adenotonsillectomy and palatoplasty, resulted in a striking amelioration of respiratory parameters and increased posterior airway space, and allowed the patient to avoid tracheotomy while awaiting for maxillo-mandibular surgery.

A case of osteosarcoma in a patient with pycnodysostosis.

Pycnodysostosis is a rare sclerosing bone dystrophy. The main clinical features are short stature and oral and maxillofacial abnormalities such as a large head, a small and underdeveloped face with prominent nose and eyes, irregular dentition, small hands and feet with dystrophic nails, and trunk deformities such as scoliosis. The differential diagnosis is established with other skeletal dysplasias such as osteopetrosis, cleidocranial dysplasia, and idiopathic acro-osteolysis. Since its first description in 1962 by Maroteaux and Lamy, about 100 cases have been published, some of these with uncommon features. We describe the case of a 22-year-old European man with pycnodysostosis who developed a chondroblastic osteosarcoma of the right femur. No case of bone cancer in this sclerosing bone disease had been described so far.