Enfrentamiento anestésico de paciente con picnodisostosis: a propósito de un caso / Anesthetic coping of a patient with pycnodysostosis: about a case

Pycnodysostosis is a rare autosomal recessive disease with osteoarticular manifestations of great relevance in anesthetic practice. People with this disease are more prone to fractures and craniofacial anomalies that anticipate a difficult-to-manage airway. We present the case of a 19-year-old woman with pycnodysostosis who underwent a reductive mammoplasty under general anesthesia. (AU)

Osteomyelitis of the jaws in patients with pycnodysostosis: a systematic review.

INTRODUCTION: Pycnodysostosis is a rare autosomal recessive syndrome that provides the abnormal bone metabolism that increases the susceptibility of patients to develop osteomyelitis. OBJECTIVE: This systematic review was conducted to analyze the risk factors associated with the development of complications in the jaws (fractures and osteomyelitis), as well as their clinical-pathological characteristics and therapeutic approaches in patients with pycnodysostosis. METHODS: Searches were performed in the PubMed, Web of Science, Scopus, Lilacs, and Cochrane databases. Case reports or case series that met the eligibility criteria according to the PRISMA statement were included. The full texts of 31 articles were retrieved. Twenty of these articles published between 1969 and 2018 were selected, which described 26 cases of osteomyelitis in patients with pycnodysostosis. RESULTS: The mean age of the patients was 37.84 years; the male-to-female was 1.36:1. The mandible was the most affected site (76.9%). Tooth extraction was the main risk factor for osteomyelitis (61.5%), followed by infection (26.8%) and mandibular fracture (23.0%). Antibiotic therapy alone or combined with some surgical procedure was the treatment used in most cases (80.7%). CONCLUSION: The findings of this review showed that patients with pycnodysostosis are more likely to develop osteomyelitis of the jaws after surgical procedures, especially tooth extraction which remains the main risk factor for its establishment. In addition, prophylactic antibiotic-therapy in the pre- and postoperative periods may prevent the development of osteomyelitis in pycnodysostosis.

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.

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

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, «birds 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.

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.

Oral Lesions in Pycnodysostosis Syndrome: Eleven Years of Follow-Up.

Pycnodysostosis is a rare genetic disease that is characterized by osteosclerosis, short stature, and bone fragility. There are not cases of gnathic bones lesions reported on the international literature. This study aims to describe a clinical case of a 10-year-old girl with pycnodysostosis syndrome and an uncommon association with 4 distinct lesions (dentigerous cyst, central giant cell lesions, and 2 fibro-osseous lesions).

Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region.

BACKGROUND: Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceará State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis. METHODS: The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceará, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents. RESULTS: We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceará State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceará (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceará have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast. CONCLUSIONS: The high frequency of pycnodysostosis in Ceará State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceará, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceará, suggestive of a founder effect.

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.

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...

Morphological features of pycnodysostosis with emphasis on clinical and radiographic maxillofacial findings / Características morfológicas de la picnodisostosis con énfasis en hallazgos clínicos y radiológicos maxilofaciales

Pycnodysostosis is a rare genetic syndrome characterized by short stature, obtuse mandibular angle, frontal, parietal and occipital bossing, open fontanels and cranial sutures, midfacial hypoplasia, acro-osteolysis of the distal phalanges, increased bone density, absence or hipopneumatization of the paranasal sinuses and normal laboratory studies. We report the case of a 35-year-old Brazilian man that was referred to a private clinic with history of dysmorphic facies for evaluation. The clinical and radiological features exhibited by the patient led to a diagnosis of pycnodysostosis. We describe the morphological features of pycnodysostosis with emphasis on the clinical and radiographic maxillofacial findings comparing the data obtained from our case with a literature review.

La picnodisostosis es un síndrome genético raro caracterizado por baja estatura, ángulo de la mandíbula obtuso, prominencias frontal, parietal y occipital, suturas craneales y fontanelas abiertas, hipoplasia del tercio medio de la cara, acroosteolisis de las falanges distales, aumento de la densidad ósea, ausencia o hiponeumatización de los senos paranasales y exámenes de laboratorio normales. Se presenta un caso de paciente brasileño, 35 años de edad, sexo masculino, remitido a clínica privada con historia de facies dismórfico para evaluación. Las características clínicas y radiológicas exhibidas por el paciente llevaron al diagnóstico de picnodisostosis. Se describe las características morfológicas de la picnodisostosis con énfasis en los hallazgos clínicos y radiológicos maxilofaciales, comparando los datos obtenidos en nuestro caso con los hallazgos reportados en la literatura revisada.

A subcranial Le Fort III advancement with distraction osteogenesis as a clinical strategy to approach pycnodysostosis with midface retrusion and exorbitism.

Pycnodysostosis is a rare autosomal recessive skeletal disorder involving a constellation of craniofacial manifestations including midface retrusion. We report the case of a 13-year-old girl with pycnodysostosis who presented with exorbitism, midface retrusion, malocclusion, and obstructive sleep apnea. Here, we describe the successful use of subcranial Le Fort III advancement using distraction osteogenesis with internal Kawamoto distracters. After a latency of 5 days, distraction for 10 days, and consolidation for 12 weeks, her midface was advanced by 10 mm with slight overcorrection at the occlusion level. At 2 years postoperatively, the patient had complete remission of her sleep apnea, resolution of her exorbitism, and amelioration of her class III malocclusion to class I. To the best of our knowledge, this is the first report of a successful subcranial Le Fort III midface advancement with distraction osteogenesis for craniofacial reconstruction of a pycnodysostosis. Our report highlights the surgical options that have been described for this craniofacial deformity and presents a novel and expedient approach for patients with pycnodysostosis presenting with exorbitism, midface retrusion, and/or sleep apnea.

Pycnodysostosis with craniosynostosis: case report of the craniofacial and oral features.

Pycnodysostosis (OMIM 265800) is an uncommon hereditary disorder characterized by osteosclerosis of the skeleton, short stature, and bone fragility. The syndrome was first described by Maroteaux and Lamy (1962). Facial dysmorphology, hypoplasia of the mandible,dysplasia of the skull, bones with delayed closure of the cranial sutures, clavicular dysplasia, acroosteolysis or partial aplasia of the terminal phalanges, and abnormal tooth eruption have also been reported (Gelb et al., 1995). An autosomal recessive mode of inheritance has been also suggested and the locus of the disease was initially mapped to human chromosome 1q21 by genetic linkage (Bernard et al., 1980). Since then, several mutations on unrelated patients and consanguineous families have been identified in the cathepsin K gene (CTSK), affecting osteoclast function.Only two previous reports have demonstrated the presence of craniosynostosis in patients with pycnodysostosis(Fleming et al., 2007; Osimani et al., 2010). The purpose of this case report is to describe the craniofacial and dental features of a 12-year-old boy with pycnodysostosisand an uncommon association with craniosynosotosis.

Familial pycnodysostosis: identification of a novel mutation in the CTSK gene (cathepsin K).

BACKGROUND: Pycnodysostosis, an autosomal recessive skeletal dysplasia, is characterized by short stature, osteosclerosis, delayed cranial suture closure, hypoplastic mandible, acro-osteolysis, hypoplastic clavicle, and dental anomalies. The disorder is caused by CTSK gene defects, a gene localized on 1q21. PURPOSE: To describe the clinical, radiological, and molecular findings in a family with pycnodysostosis. METHODS: The CTSK gene was analyzed from genomic DNA in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis and 100 healthy controls. RESULTS AND INTERPRETATION: We identified the novel homozygous mutation c.908G>A within exon 8 of the CTSK gene. This missense mutation leads to the substitution of the amino acid glycine at position 303 by glutamic acid (G303E) in cathepsin K protease. No genotype/phenotype correlation was present in affected members of the family with pycnodysostosis.

Pyknodysostosis: oral findings and differential diagnosis.

Pyknodysostosis is a rare, genetic, autosomal recessive condition characterized by short stature, generalized bone sclerosis, and oral manifestations such as maxillary atresia and an increase of the mandibular angle. The main purpose of this article was to report a case of pyknodysostosis, describing the characteristic orofacial findings of the disease and discussing the differential diagnosis.

Pycnodysostosis - abstract

Pycnodysostosis, a rare bone disease is characterized by marble bone-like esseous deviations combined with multiple dysostosis. Physically there is a short stature. The head is broad with a froglike expression. The hands and feet are shortened with typical digital and nail anomalies however not always fully expressed. Clinically the disease is marked by multiple spontaneous fractures, and osteomyelitis of lower and upper jaw occurs frequently. In young children, probably due to the absence of the maxillary sinus, pulmonary complications occur, sometimes with a fatal outcome. Haematologically, it runs a benign course; leucocytosis and severe anaemia as in marble bone disease, were not observed. Genetically, is a recessive dominant disease and no chromosomal deviations could be demonstrated. The typical roentgenological features were present. Two families from Curacao and Bonaire were investigated and intermarriage consanguinity was present (AU)