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1.
Eur J Med Genet ; 67: 104904, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38141876

ABSTRACT

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.


Subject(s)
Fractures, Spontaneous , Mandibular Fractures , Pycnodysostosis , Female , Humans , Middle Aged , Fractures, Spontaneous/genetics , Fractures, Spontaneous/complications , Mandible/pathology , Mandibular Fractures/complications , Mandibular Fractures/genetics , Pycnodysostosis/complications , Pycnodysostosis/genetics , Pycnodysostosis/pathology , Quality of Life
2.
BMJ Case Rep ; 16(9)2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37723084

ABSTRACT

Pycnodysostosis is a rare genetic condition that leads to generalised bony sclerosis and increased fracture risk. Orthopaedic specialists play a crucial role in managing affected children due to their susceptibility to frequent fractures. We had a case of a middle childhood female patient with pycnodysostosis and a femur fracture. Initially, an attempt using the Titanium Elastic Nailing System was made, but the sclerotic metaphyseal bone made it challenging. So, we opted for a 4.5 mm locked compressive plate, with multiple drill bits as a backup due to potential drill breakage. Though elastic nailing is preferred for paediatric long bone fractures, surgeons must be prepared for extremely sclerotic cortices and a narrow medullary canal when dealing with patients with pycnodysostosis. Open fixation and multiple drill bits in the toolkit are essential to overcome the potential obstacles during the procedure.


Subject(s)
Adrenal Medulla , Femoral Fractures , Pycnodysostosis , Humans , Child , Female , Pycnodysostosis/complications , Femoral Fractures/diagnostic imaging , Femoral Fractures/etiology , Femoral Fractures/surgery , Patients , Bone Plates , Rare Diseases
4.
Orthopadie (Heidelb) ; 51(12): 1010-1014, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36161513

ABSTRACT

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.


Subject(s)
Fractures, Spontaneous , Pycnodysostosis , Tibial Fractures , Female , Humans , Child, Preschool , Pycnodysostosis/complications , Tibial Fractures/complications , Tibia/diagnostic imaging , Fractures, Spontaneous/complications
5.
J Ayub Med Coll Abbottabad ; 34(1): 216-219, 2022.
Article in English | MEDLINE | ID: mdl-35466658

ABSTRACT

Pycnodysostosis is a rare disease with very few reported cased all over the world. It was first described in 1963 by Maroteaux and Lamy. It is also known as Toulouse-Lautrec syndrome, after a French artist, Henri de Toulouse Lautrec. The affected gene, CTSK, was first isolated in 1996. It is an autosomal recessive osteochondrodysplasia, characterized by disrupted function of osteoclasts. Incidence of this disease is 1.7 per 1 million births with a male to female ratio of 1:1 30% cases arise from consanguineous marriages.


Subject(s)
Pycnodysostosis , Consanguinity , Female , Humans , Male , Pycnodysostosis/complications , Pycnodysostosis/diagnosis , Pycnodysostosis/genetics , Rare Diseases
6.
Orthod Craniofac Res ; 25(4): 494-501, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34963019

ABSTRACT

AIM: To assess the upper airway (UA) morphology in patients with pycnodysostosis with a 3D analysis, compare results with normative data and investigate the correlation of the total volume (TV) with other UA morphology variables. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images of eight Danish patients with pycnodysostosis (4 males and 4 females with a mean age of 31.8 years, SD: 16.3 years) were analyzed using Mimics® (Materialise® ) and compared with a sex- and age-matched control group (6 males and 8 females with a mean age of 33.6 years, SD: 18.6 years). RESULTS: The distance from the tip of the epiglottis (E) to the Frankfurt horizontal plane (Fp) was significantly shorter in the pycnodysostosis group (P < .042). Regarding the cross-sectional measurements, at the 'maximum constriction' (P < .005), the 'upper airway limit' (P < .001) and the 'lower airway limit' (P < .035) cross-sections were significantly smaller in the pycnodysostosis group. The volumes 'nasopharynx' (P < .002) and 'total airway' (TV) (P < .01) were also significantly smaller. CONCLUSION: Patients with pycnodysostosis have a reduced total airway as well as nasopharyngeal volume compared with matched controls. Additionally, they have a reduced cross-sectional area in the upper and lower borders of the UA, and the area of maximum constriction is also reduced. These factors might explain the high prevalence of obstructive sleep apnoea in pycnodysostosis. Total airway is positively correlated with total length and cross-sections at all levels including the maximum constriction area as well as the anteroposterior dimension at the upper and lower airway borders.


Subject(s)
Pycnodysostosis , Sleep Apnea, Obstructive , Adolescent , Adult , Cone-Beam Computed Tomography , Female , Humans , Imaging, Three-Dimensional/methods , Male , Nasopharynx , Pharynx/anatomy & histology , Pharynx/diagnostic imaging , Pycnodysostosis/complications , Pycnodysostosis/diagnostic imaging , Sleep Apnea, Obstructive/diagnostic imaging
7.
Braz J Otorhinolaryngol ; 87(5): 620-628, 2021.
Article in English | MEDLINE | ID: mdl-33579598

ABSTRACT

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.


Subject(s)
Osteomyelitis , Pycnodysostosis , Adult , Female , Humans , Male , Mandible , Pycnodysostosis/complications
10.
J Clin Res Pediatr Endocrinol ; 12(4): 444-449, 2020 11 25.
Article in English | MEDLINE | ID: mdl-32248673

ABSTRACT

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.


Subject(s)
Abnormalities, Multiple/drug therapy , Human Growth Hormone/administration & dosage , Hypothyroidism/drug therapy , Pituitary Hormones, Anterior/deficiency , Pituitary Hormones/deficiency , Pycnodysostosis/drug therapy , Thyroxine/administration & dosage , Transcription Factor Pit-1/deficiency , Abnormalities, Multiple/pathology , Child , Facies , Female , Humans , Hypothyroidism/complications , Hypothyroidism/pathology , Prognosis , Pycnodysostosis/complications , Pycnodysostosis/pathology
11.
Am J Med Genet A ; 182(1): 122-129, 2020 01.
Article in English | MEDLINE | ID: mdl-31680459

ABSTRACT

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.


Subject(s)
Pycnodysostosis/physiopathology , Sleep Apnea Syndromes/physiopathology , Sleep Apnea, Obstructive/physiopathology , Child , Child, Preschool , Continuous Positive Airway Pressure/methods , Female , Humans , Infant , Male , Polysomnography , Pycnodysostosis/complications , Pycnodysostosis/surgery , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/surgery , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/surgery
12.
Calcif Tissue Int ; 105(6): 681-686, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31489468

ABSTRACT

Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.


Subject(s)
Fractures, Multiple/genetics , Hypophosphatasia/genetics , Mutation/genetics , Pycnodysostosis/genetics , Alkaline Phosphatase/genetics , Bone and Bones/metabolism , Cathepsin K/genetics , Female , Fracture Healing/genetics , Fractures, Bone/complications , Fractures, Bone/genetics , Humans , Hypophosphatasia/complications , Male , Pycnodysostosis/complications
13.
J Craniofac Surg ; 30(1): 110-114, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30394969

ABSTRACT

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.


Subject(s)
Craniosynostoses/surgery , Papilledema/etiology , Pycnodysostosis/surgery , Sleep Apnea, Obstructive/etiology , Child , Craniosynostoses/complications , Female , Humans , Intracranial Hypertension/etiology , Osteogenesis, Distraction , Pycnodysostosis/complications
14.
Acta ortop. mex ; 32(5): 291-296, Sep.-Oct. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-1124111

ABSTRACT

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.


Subject(s)
Humans , Pycnodysostosis/complications , Pycnodysostosis/diagnosis , Fractures, Spontaneous/etiology , Retrospective Studies , Follow-Up Studies , Cathepsin K/genetics
15.
J Oral Maxillofac Surg ; 76(10): 2136.e1-2136.e10, 2018 10.
Article in English | MEDLINE | ID: mdl-30030999

ABSTRACT

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.


Subject(s)
Adipose Tissue/transplantation , Anti-Bacterial Agents/therapeutic use , Mandibular Diseases/therapy , Oral Surgical Procedures , Osteomyelitis/therapy , Pycnodysostosis/complications , Adult , Female , Humans
17.
Eur J Orthop Surg Traumatol ; 28(6): 1231-1233, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29480369

ABSTRACT

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.


Subject(s)
Cervical Vertebrae/injuries , Fracture Dislocation/diagnostic imaging , Pycnodysostosis/diagnosis , Spinal Fractures/diagnostic imaging , Accidental Falls , Cervical Vertebrae/diagnostic imaging , Fractures, Spontaneous , Humans , Male , Pycnodysostosis/complications , Spinal Fractures/etiology , Young Adult
18.
Acta Ortop Mex ; 32(5): 291-296, 2018.
Article in Spanish | MEDLINE | ID: mdl-30726592

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, «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.


Subject(s)
Fractures, Spontaneous , Pycnodysostosis , Cathepsin K/genetics , Follow-Up Studies , Fractures, Spontaneous/etiology , Humans , Pycnodysostosis/complications , Pycnodysostosis/diagnosis , Retrospective Studies
19.
Int J Pediatr Otorhinolaryngol ; 95: 91-96, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28576543

ABSTRACT

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.


Subject(s)
Adenoidectomy/methods , Pycnodysostosis/diagnosis , Tonsillectomy/methods , Adenoidectomy/adverse effects , Adenoids/pathology , Adolescent , Cephalometry , Child , Diagnosis, Differential , Female , Humans , Male , Otolaryngology , Palatine Tonsil/pathology , Polysomnography , Pycnodysostosis/complications , Pycnodysostosis/therapy , Quality of Life , Retrospective Studies , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/surgery , Sleep Apnea, Obstructive/surgery , Tonsillectomy/adverse effects
20.
Medicine (Baltimore) ; 96(50): e8730, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29390266

ABSTRACT

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.


Subject(s)
Carcinoma, Neuroendocrine/complications , Cathepsin K/genetics , Mutation , Pycnodysostosis/genetics , Thyroid Neoplasms/complications , Adult , Carcinoma, Neuroendocrine/surgery , Female , Humans , Neck Dissection , Pycnodysostosis/complications , Thyroid Neoplasms/surgery , Thyroidectomy
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