The Egyptian Journal of Radiology and Nuclear Medicine xxx (2016) xxx–xxx
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The Egyptian Journal of Radiology and Nuclear Medicine
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Case Report Pseudoachondroplasia in a child: The role of anthropometric measurements and skeletal imaging in differential diagnosis ⇑ Radwa Gamal, MSc a, Solaf M. Elsayed, MD a, Tamer Ahmed EL-Sobky, MD b, , Heba Salah Elabd, MD a a Department of Paediatrics, Division of Medical Genetics, Faculty of Medicine, Ain-Shams University, 11591 Abbassia, Cairo, Egypt b Department of Orthopaedic Surgery, Division of Paediatric Orthopaedics, Faculty of Medicine, Ain-Shams University, 11591 Abbassia, Cairo, Egypt article info abstract
Article history: Pseudoachondroplasia is a rare osteochondrodysplasia characterized by disproportionate short stature Received 3 May 2016 and limb deformity. Diagnostic accuracy is based on a detailed evaluation of the radioclinical features. Accepted 22 October 2016 We report a boy with pseudoachondroplasia. We aim to underscore why is accurate delineation of the Available online xxxx pattern of radioclinical skeletal abnormalities in pseudoachondroplasia a weighty part of diagnosis. Furthermore, we aim to highlight the main clinical and skeletal imaging features of skeletal dysplasias Keywords: that overlap with pseudoachondroplasia using clinical cases evaluated in our institution. The findings Paediatric musculoskeletal imaging affirm that anthropometric measurements and skeletal radiography are important contributors to the dif- Short limb disproportionate dwarfism ferential diagnosis and classification of disproportionate growth. Short stature Ó Arthrogenic osteochondrodysplasia 2016 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This Genetic bone dysplasia is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ Plain radiography 4.0/).
1. Introduction PSACH an integral part of the diagnostic process. The second objec- tive was to highlight the main clinical and plain radiographic fea- Pseudoachondroplasia (PSACH) is an osteochondrodysplasia tures of skeletal dysplasias that overlap with PSACH using characterized by disproportionate short stature, deformity of the clinical cases evaluated in our institution. lower limbs, short fingers, and ligamentous laxity. It affects at least 1 in 20,000 individuals [1]. Pseudoachondroplasia is inherited in an 2. Case presentation autosomal dominant manner and is caused exclusively by muta- tions in the cartilage oligomeric matrix protein COMP gene [2]. A 4- and half year-old boy, the fourth in order of birth of healthy It’s characterized by a moderately severe form of disproportionate non-consanguineous Egyptian parents presented to our outpatient short-limb short stature. A common presenting feature is a wad- clinic. The patient was delivered at full term by vaginal delivery dling gait, recognized at the onset of walking. An accurate diagno- after an uncomplicated pregnancy. The parents noticed gait abnor- sis of a skeletal dysplasia in general and PSACH in specific is still malities of their child that began two years ago. Motor and cogni- based on a detailed evaluation of clinical and radiographic findings. tive milestones were normal. The family history was Early diagnosis, and timely and appropriate treatment of skeletal unremarkable. Both parents were phenotypically normal with no dysplasia are critical in preventing or arresting functional deterio- abnormal craniofacial features. Cardiac, chest, abdominal and gen- ration and complications. Diagnostic accuracy is essential for prog- ital examinations were clinically normal. No neurologic abnormal- nostication and genetic counselling [2–6]. We report the ities were detected. musculoskeletal manifestations of a boy with PSACH. The first objective of this study was to underscore why is accurate delin- 2.1. Anthropometric measurements eation of the pattern of radioclinical skeletal abnormalities in The patient exhibited disproportionately short limb short sta- ture with no trunk shortening. The height for age measured Peer review under responsibility of The Egyptian Society of Radiology and Nuclear 83.5 cm; <3rd percentile. The lower-body segment measured Medicine. 29 cm; <3rd percentile. The sitting height was unremarkable. ⇑ Corresponding author. Upper/lower-body segment (U/L) ratio recorded 1.8. The sitting E-mail addresses: [email protected] (R. Gamal), elsayed683@yahoo. com (S.M. Elsayed), [email protected], [email protected] height/height (SH/H) ratio recorded 0.65; >97th percentile. The (T.A. EL-Sobky), [email protected] (H.S. Elabd). arm span measured 6 cm shorter than the height. http://dx.doi.org/10.1016/j.ejrnm.2016.10.007 0378-603X/Ó 2016 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Gamal R et al. . Egypt J Radiol Nucl Med (2016), http://dx.doi.org/10.1016/j.ejrnm.2016.10.007 2 R. Gamal et al. / The Egyptian Journal of Radiology and Nuclear Medicine xxx (2016) xxx–xxx
2.2. Musculoskeletal manifestations from achondroplasia. These findings are in concordance with the diagnosis of PSACH. The patient demonstrated bilateral symmetrical mild fixed flex- The majority of skeletal dysplasias is characterized by short sta- ion and moderate valgus deformity of both knees with compen- ture that may be proportionate or disproportionate. Disproportion- satory hyperlordosis of lumbar spine. Both feet exhibited rocker ate short stature can be further classified according to the parts of bottom deformity. The hands exhibited brachydactyly (Fig. 1A–C). the body in which there is reduced growth: (a) Short limb short No extra-skeletal affection was reported. Neurologic examination stature in which there is limb shortening as achondroplasia, revealed normal results. Spot test screening for mucopolysacchari- hypochondroplasia, PSACH and multiple epiphyseal dysplasia dosis was negative. The two-dimensional electrophoretic separa- (MED) and (b) Short trunk short stature in which there is trunk tion for urinary glycosaminoglycans revealed normal pattern shortening as spondyloepiphyseal dysplasia and mucopolysaccha- excluding mucopolysaccharidosis. Serum calcium, phosphorus, ridosis [3,8–10]. alkaline phosphatase and thyroid profile were unremarkable. Therefore, an integral parameter of physical examination is anthropometric measurements such as height, sitting height, arm span, U/L ratio, SH/H ratio, and arm span/height ratio for age. It also 2.3. Imaging findings includes a description of the limb involvement depending on the primarily involved segment of the limb. The condition can be A skeletal survey of the axial and appendicular skeleton was described as rhizomelic (humerus and femur), mesomelic (radius, performed to characterize and evaluate the extent of the disease. ulna, tibia and fibula) and acromelic (hands and feet). Anthropo- The plain radiographs depicted a wide array of manifestations metric measurements provide an objective basis for recognizing attributed to affection of epimetaphyseal regions of long bones and classifying disproportionate growth and aid in differential and vertebral bodies (Figs. 2A–D and 3A–C). Our patient’s parents diagnosis [11–13]. The mentioned ratios change with age. U/L ratio were informed that data about the case would be submitted for is 1.7 in the newborn; approximately 1.0 between ages 2 and publication. No financing was received for this study. The study 8 years; 0.95 as an adult. A short statured patient with short trunk was authorized by the local ethical committee. will have a decreased U/L ratio, and an arm span exceeding height, while an individual with normal trunk and relatively short limbs 3. Discussion will have an increased U/L ratio, and an arm span shorter than height [3,4,12,13]. Our patient’s height fell below the 3rd per- In skeletal dysplasia the accurate history regarding time of centile for age (>2 SD below the mean), readily labelling him as a onset of short stature is essential prior to physical examination. dwarf. His sitting height was normal for age, while the lower- Patients with Spondyloepiphyseal dysplasia congenita are usually body segment length fell below the 3rd percentile for age (>2 SD evident at birth with disproportionately short stature while below the mean). Moreover the U/L ratio recorded 1.8, the SH/H patients with spondyloepiphyseal dysplasia tarda exhibit retarded ratio recorded 0.65, and the arm span measures 6 cm shorter than linear growth beginning around age five to eight years [7,8]. In con- the height. The previous anthropometric measurements of our trast, patients affected with PSACH typically exhibit disproportion- patient are consistent with disproportionate short limb short sta- ately short stature or a waddling gait by approximately age two ture. The literature citations that categorize PSACH as a dispropor- years [1–3]. Our patient had normal length at birth and exhibited tionate short limb short stature and the findings reported in our growth retardation and gait abnormality at around the age two patient are in agreement [1–3,10]. years. Moreover the patient had normal fascial appearance and Moreover, numerous characteristic clinical orthopaedic no trident hands that serve as additional differentiating criteria manifestations of PSACH reported in the literature have been
Fig. 1. (A–C) Our 4- and a half year-old patient with PSACH. Note the flexion deformity of the hips, knees, hyperlordosis of lumbar spine, rocker bottom feet, and shortening of proximal limb segments (humeri and femora) (rhizomelic shortening) with broadening of the metaphyseal ends of long bones especially around the wrists, knees and ankles (A), genu valgum (B), and brachydactyly (C).
Please cite this article in press as: Gamal R et al. . Egypt J Radiol Nucl Med (2016), http://dx.doi.org/10.1016/j.ejrnm.2016.10.007 R. Gamal et al. / The Egyptian Journal of Radiology and Nuclear Medicine xxx (2016) xxx–xxx 3
Fig. 2. (A–D) A radiographic survey of the pelvis and appendicular skeleton (same patient). Anteroposterior radiographs of the pelvis and both hips (A), depicting undersized capital femoral epiphyses, broad short femoral necks, coxa vara, horizontality of acetabular roof and absent epiphyseal centre of os pubis and greater trochanter. Lesions are bilateral and symmetrical an important distinguishing feature from Perthes disease. Radiographic findings of Perthes disease are characteristically asymmetrical and occasionally unilateral as shown in a 3-year-old boy (B). Radiographs of both shoulders depicting (C), dysplastic proximal humeral epiphyses, metaphyseal broadening, irregularity and metaphyseal line of ossification. Radiographs of the legs (D) depicting hypoplastic distal femoral (solid arrows) and proximal tibial epiphyses, metaphyseal broadening, irregularities and radiolucent areas especially medially (stars). Note the metaphyseal line of ossification of the proximal tibias (hollow arrows) and relative sparing of the tibial shafts. Lesions are bilateral and symmetrical. The described metaphyseal lesions of long bones simulate radiographic appearance of rickets ‘‘rachitic-like lesions”. See the radiographic differential diagnosis of pseudoachondroplasia, figure (4C, D).
demonstrated in our patient. These findings include waddling gait spine ribs and pelvis, and (b) defining dysplasia involving the recognized at the onset of walking, ligamentous laxity, lumbar lor- appendicular skeleton and further delineating the anatomic areas dosis, moderate brachydactyly and valgus deformity of the knees of affection i.e. proximal, middle and distal segments of the limbs. [1–3,10]. There is considerable overlap between PSACH and MED The geographic area of affection inside the bone segment involved with respect to age of presentation and radiographic appearance is then further identified i.e. epiphyseal, metaphyseal and diaphy- in both entities [9,10]. Nevertheless the presence of marked and seal or a combination; (c) finally reporting abnormalities in bone characteristic radiographic spinal and pelvic involvement, joint density and configuration. The radiographic differential diagnosis laxity and significant metaphyseal changes argues for PSACH. It of skeletal dysplasias that overlap with PSACH is presented using is noteworthy that some spinal abnormalities including bullet- clinical cases evaluated in our institution (Fig. 4A–G). We plan to shaped (oval) vertebral bodies (superior and inferior endplate subject our patient to guided growth surgery in the near future, rounding) may occur in patients with MED caused by mutations to address the valgus deformity of his knees. We will conduct reg- in COMP and MATN3 genes [14]. ular follow-up examinations for evidence of lower limb and spine Odontoid hypoplasia is not a common finding but does some- deformities, symptomatic joint hypermobility, degenerative joint times occur leading to cervical spine instability [2]. Our patient disease, and neurologic manifestations, particularly spinal cord did not demonstrate radiographic signs of atlantoaxial instability. compression related to atlantoaxial instability. The radiographic abnormalities shown in our patient were con- sistent with those demonstrated in already known types of PSACH 3.1. Genetic profiling [1–3,10]. Radiographic evaluation of skeletal dysplasias causing disproportionate short stature is an important contributor to accu- Pseudoachondroplasia is inherited in an autosomal dominant rate diagnosis. Delineating the pivotal and differentiating skeletal manner due to mutations in the COMP gene, though one case of a radiographic features aid in differential diagnosis. This requires fol- very rare autosomal recessive form has been documented. When lowing a systematic approach based on set radiographic guidelines neither parent of a proband with pseudoachondroplasia has clini- as (a) defining dysplasias involving the axial skeleton and further cal evidence of the disorder, it is likely that the proband has a de delineating the anatomic areas of affection i.e. skull, mandible, novo pathogenic mutation as seen in our patient [15,16]. Cartilage
Please cite this article in press as: Gamal R et al. . Egypt J Radiol Nucl Med (2016), http://dx.doi.org/10.1016/j.ejrnm.2016.10.007 4 R. Gamal et al. / The Egyptian Journal of Radiology and Nuclear Medicine xxx (2016) xxx–xxx
Fig. 3. (A–C) A radiographic survey of axial skeleton (same patient). Lateral radiographs of the cervical spine (A) depicting oval shaped vertebrae and platyspondyly. Lateral radiographs of the dorsolumbar spine (B) depicting oval shaped vertebrae with anterior beak originating from the central portion of vertebral body (arrows). Anteroposterior radiographs of the dorsolumbar spine (C) demonstrating normal widening of the interpedicular distances caudally. In contrast, achondroplasic patients exhibit unchanged or narrow interpedicular distance. This is an important distinguishing radiographic feature. oligomeric matrix protein (COMP) is an extracellular matrix pro- radiologic manifestations can help in prioritizing the genes to be tein found primarily in cartilage and other musculoskeletal tissues. sequenced in the context of PSACH and the MED disease spectrum This gene provides instructions for making a protein that is essen- [14,18–20]. tial for the normal development of cartilage and for its conversion to bone [17]. Mutations in COMP gene result in protein misfolding and intracellular retention inside the chondrocyte which leads to 3.2. Conclusion early chondrocytes death and ultimately prevents normal bone growth causing short stature and bone abnormalities in pseudoa- Our study findings affirm the conclusions of previous literature chondroplasia [15]. Likewise the largest proportion of autosomal reports that anthropometric measurements provide an objective dominant MED (AD-MED) results from mutations in COMP gene; basis for recognizing and classifying disproportionate growth and however, AD-MED is genetically heterogenous and can also result aid in differential diagnosis [11–13]. Accurate diagnosis remains from mutations in matrilin-3 (MATN3) and type IX collagen largely based on appropriate history taking, with the unique clini- (COL9A1, COL9A2, and COL9A3). In contrast, autosomal recessive cal and radiographic skeletal findings. Efficient and effective team- MED appears to result exclusively from mutations in sulphate work between paediatrician, geneticist, radiologist and paediatric transporter solute carrier family 26 (SLC26A2) [14,18–21]. Several orthopaedic surgeon in the evaluation process of PSACH is para- studies have documented that meticulous evaluation of skeletal mount to accurate diagnosis.
Please cite this article in press as: Gamal R et al. . Egypt J Radiol Nucl Med (2016), http://dx.doi.org/10.1016/j.ejrnm.2016.10.007 R. Gamal et al. / The Egyptian Journal of Radiology and Nuclear Medicine xxx (2016) xxx–xxx 5
Fig. 4. (A–G) Radiographic differential diagnosis of PSACH. Achondroplasia. Radiographs of the pelvis and lower limbs of a neonate (A) depicting symmetrical rhizomelic (femoral) shortening of long bones, flaring and splaying of metaphyses with normal epiphyses (arrows). Note squaring of iliac wings with rounding of corners and flat horizontal acetabuli. Lateral radiographs of the dorsolumbar spine (B) depicting hypoplastic bullet shaped vertebrae with anterior wedging. Rickets. Radiographs of both legs of a child with healing rickets (C) depicting metaphyseal broadening, cupping and metaphyseal line of ossification (arrows), especially around the knee. Mark that epiphyseal density and configuration are retained. Radiographs of both legs of a child with active rickets (D) depicting metaphyseal broadening, cupping and fraying around the knees. Note the absence of the metaphyseal line of ossification found in the previous patient with healing rickets besides mottling and rarefaction of epiphyses around the knees (arrows). Additionally distal tibial and fibular diaphyseal deformities are depicted. Morquio syndrome (mucopolysaccharidosis type IV). Lateral radiographs of dorsolumbar spine (E) in a 7-year-old female child depicting various degrees of platyspondyly, anterior beaking mainly arising from inferior portion of vertebral body, dorsolumbar kyphosis, and broadened ribs especially anterior. Radiographs of her pelvis and both hips (F) depicting coxa valga shallow acetabuli and epiphyseal changes mimicking bilateral Perthes disease. Lesions are characteristically bilateral and symmetrical an important distinguishing feature from Perthes disease. Osteogenesis imperfecta type III. Lateral radiographs of dorsal spine (G) in a 6-year-old boy. Mark the generalized bone rarefaction, various degrees of platyspondyly (solid white arrows), biconcave vertebral wedging (black arrows), and anterior wedging (hollow white arrows).
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