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 anthropometricmeasurements and skeletal imaging in differential diagnosis

http://dx.doi.org/10.1016/j.ejrnm.2016.10.0070378-603X/� 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/).

Peer review under responsibility of The Egyptian Society of Radiology and NuclearMedicine.⇑ Corresponding author.

E-mail addresses: drradwagamal@yahoo.com (R. Gamal), elsayed683@yahoo.com (S.M. Elsayed), tamersh@hotmail.com, tamer.ahmed@med.asu.edu.eg(T.A. EL-Sobky), hsalahabd@yahoo.com (H.S. Elabd).

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

Radwa Gamal, MSc a, Solaf M. Elsayed, MD a, Tamer Ahmed EL-Sobky, MD b,⇑, Heba Salah Elabd, MD a

aDepartment of Paediatrics, Division of Medical Genetics, Faculty of Medicine, Ain-Shams University, 11591 Abbassia, Cairo, EgyptbDepartment of Orthopaedic Surgery, Division of Paediatric Orthopaedics, Faculty of Medicine, Ain-Shams University, 11591 Abbassia, Cairo, Egypt

a r t i c l e i n f o

Article history:Received 3 May 2016Accepted 22 October 2016Available online xxxx

Keywords:Paediatric musculoskeletal imagingShort limb disproportionate dwarfismShort statureArthrogenic osteochondrodysplasiaGenetic bone dysplasiaPlain radiography

a b s t r a c t

Pseudoachondroplasia is a rare osteochondrodysplasia characterized by disproportionate short statureand limb deformity. Diagnostic accuracy is based on a detailed evaluation of the radioclinical features.We report a boy with pseudoachondroplasia. We aim to underscore why is accurate delineation of thepattern 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 dysplasiasthat overlap with pseudoachondroplasia using clinical cases evaluated in our institution. The findingsaffirm that anthropometric measurements and skeletal radiography are important contributors to the dif-ferential diagnosis and classification of disproportionate growth.� 2016 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. Thisis an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/

4.0/).

1. Introduction

Pseudoachondroplasia (PSACH) is an osteochondrodysplasiacharacterized by disproportionate short stature, deformity of thelower limbs, short fingers, and ligamentous laxity. It affects at least1 in 20,000 individuals [1]. Pseudoachondroplasia is inherited in anautosomal dominant manner and is caused exclusively by muta-tions in the cartilage oligomeric matrix protein COMP gene [2].It’s characterized by a moderately severe form of disproportionateshort-limb short stature. A common presenting feature is a wad-dling gait, recognized at the onset of walking. An accurate diagno-sis of a skeletal dysplasia in general and PSACH in specific is stillbased on a detailed evaluation of clinical and radiographic findings.Early diagnosis, and timely and appropriate treatment of skeletaldysplasia are critical in preventing or arresting functional deterio-ration and complications. Diagnostic accuracy is essential for prog-nostication and genetic counselling [2–6]. We report themusculoskeletal manifestations of a boy with PSACH. The firstobjective of this study was to underscore why is accurate delin-eation of the pattern of radioclinical skeletal abnormalities in

PSACH an integral part of the diagnostic process. The second objec-tive was to highlight the main clinical and plain radiographic fea-tures of skeletal dysplasias that overlap with PSACH usingclinical cases evaluated in our institution.

2. Case presentation

A 4- and half year-old boy, the fourth in order of birth of healthynon-consanguineous Egyptian parents presented to our outpatientclinic. The patient was delivered at full term by vaginal deliveryafter an uncomplicated pregnancy. The parents noticed gait abnor-malities of their child that began two years ago. Motor and cogni-tive milestones were normal. The family history wasunremarkable. Both parents were phenotypically normal with noabnormal craniofacial features. Cardiac, chest, abdominal and gen-ital examinations were clinically normal. No neurologic abnormal-ities were detected.

2.1. Anthropometric measurements

The patient exhibited disproportionately short limb short sta-ture with no trunk shortening. The height for age measured83.5 cm; <3rd percentile. The lower-body segment measured29 cm; <3rd percentile. The sitting height was unremarkable.Upper/lower-body segment (U/L) ratio recorded 1.8. The sittingheight/height (SH/H) ratio recorded 0.65; >97th percentile. Thearm span measured 6 cm shorter than the height.

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2.2. Musculoskeletal manifestations

The patient demonstrated bilateral symmetrical mild fixed flex-ion and moderate valgus deformity of both knees with compen-satory hyperlordosis of lumbar spine. Both feet exhibited rockerbottom deformity. The hands exhibited brachydactyly (Fig. 1A–C).No extra-skeletal affection was reported. Neurologic examinationrevealed normal results. Spot test screening for mucopolysacchari-dosis was negative. The two-dimensional electrophoretic separa-tion for urinary glycosaminoglycans revealed normal patternexcluding mucopolysaccharidosis. Serum calcium, phosphorus,alkaline phosphatase and thyroid profile were unremarkable.

2.3. Imaging findings

A skeletal survey of the axial and appendicular skeleton wasperformed to characterize and evaluate the extent of the disease.The plain radiographs depicted a wide array of manifestationsattributed to affection of epimetaphyseal regions of long bonesand vertebral bodies (Figs. 2A–D and 3A–C). Our patient’s parentswere informed that data about the case would be submitted forpublication. No financing was received for this study. The studywas authorized by the local ethical committee.

3. Discussion

In skeletal dysplasia the accurate history regarding time ofonset of short stature is essential prior to physical examination.Patients with Spondyloepiphyseal dysplasia congenita are usuallyevident at birth with disproportionately short stature whilepatients with spondyloepiphyseal dysplasia tarda exhibit retardedlinear growth beginning around age five to eight years [7,8]. In con-trast, patients affected with PSACH typically exhibit disproportion-ately short stature or a waddling gait by approximately age twoyears [1–3]. Our patient had normal length at birth and exhibitedgrowth retardation and gait abnormality at around the age twoyears. Moreover the patient had normal fascial appearance andno trident hands that serve as additional differentiating criteria

Fig. 1. (A–C) Our 4- and a half year-old patient with PSACH. Note the flexion deformity ofproximal limb segments (humeri and femora) (rhizomelic shortening) with broadening o(A), genu valgum (B), and brachydactyly (C).

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from achondroplasia. These findings are in concordance with thediagnosis of PSACH.

The majority of skeletal dysplasias is characterized by short sta-ture that may be proportionate or disproportionate. Disproportion-ate short stature can be further classified according to the parts ofthe body in which there is reduced growth: (a) Short limb shortstature in which there is limb shortening as achondroplasia,hypochondroplasia, PSACH and multiple epiphyseal dysplasia(MED) and (b) Short trunk short stature in which there is trunkshortening as spondyloepiphyseal dysplasia and mucopolysaccha-ridosis [3,8–10].

Therefore, an integral parameter of physical examination isanthropometric measurements such as height, sitting height, armspan, U/L ratio, SH/H ratio, and arm span/height ratio for age. It alsoincludes a description of the limb involvement depending on theprimarily involved segment of the limb. The condition can bedescribed as rhizomelic (humerus and femur), mesomelic (radius,ulna, tibia and fibula) and acromelic (hands and feet). Anthropo-metric measurements provide an objective basis for recognizingand classifying disproportionate growth and aid in differentialdiagnosis [11–13]. The mentioned ratios change with age. U/L ratiois 1.7 in the newborn; approximately 1.0 between ages 2 and8 years; 0.95 as an adult. A short statured patient with short trunkwill have a decreased U/L ratio, and an arm span exceeding height,while an individual with normal trunk and relatively short limbswill have an increased U/L ratio, and an arm span shorter thanheight [3,4,12,13]. Our patient’s height fell below the 3rd per-centile for age (>2 SD below the mean), readily labelling him as adwarf. His sitting height was normal for age, while the lower-body segment length fell below the 3rd percentile for age (>2 SDbelow the mean). Moreover the U/L ratio recorded 1.8, the SH/Hratio recorded 0.65, and the arm span measures 6 cm shorter thanthe height. The previous anthropometric measurements of ourpatient are consistent with disproportionate short limb short sta-ture. The literature citations that categorize PSACH as a dispropor-tionate short limb short stature and the findings reported in ourpatient are in agreement [1–3,10].

Moreover, numerous characteristic clinical orthopaedicmanifestations of PSACH reported in the literature have been

the hips, knees, hyperlordosis of lumbar spine, rocker bottom feet, and shortening off the metaphyseal ends of long bones especially around the wrists, knees and ankles

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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 undersizedcapital femoral epiphyses, broad short femoral necks, coxa vara, horizontality of acetabular roof and absent epiphyseal centre of os pubis and greater trochanter. Lesions arebilateral and symmetrical an important distinguishing feature from Perthes disease. Radiographic findings of Perthes disease are characteristically asymmetrical andoccasionally 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, metaphysealbroadening, irregularities and radiolucent areas especially medially (stars). Note the metaphyseal line of ossification of the proximal tibias (hollow arrows) and relativesparing of the tibial shafts. Lesions are bilateral and symmetrical. The described metaphyseal lesions of long bones simulate radiographic appearance of rickets ‘‘rachitic-likelesions”. See the radiographic differential diagnosis of pseudoachondroplasia, figure (4C, D).

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demonstrated in our patient. These findings include waddling gaitrecognized at the onset of walking, ligamentous laxity, lumbar lor-dosis, moderate brachydactyly and valgus deformity of the knees[1–3,10]. There is considerable overlap between PSACH and MEDwith respect to age of presentation and radiographic appearancein both entities [9,10]. Nevertheless the presence of marked andcharacteristic radiographic spinal and pelvic involvement, jointlaxity and significant metaphyseal changes argues for PSACH. Itis noteworthy that some spinal abnormalities including bullet-shaped (oval) vertebral bodies (superior and inferior endplaterounding) may occur in patients with MED caused by mutationsin COMP and MATN3 genes [14].

Odontoid hypoplasia is not a common finding but does some-times occur leading to cervical spine instability [2]. Our patientdid not demonstrate radiographic signs of atlantoaxial instability.

The radiographic abnormalities shown in our patient were con-sistent with those demonstrated in already known types of PSACH[1–3,10]. Radiographic evaluation of skeletal dysplasias causingdisproportionate short stature is an important contributor to accu-rate diagnosis. Delineating the pivotal and differentiating skeletalradiographic features aid in differential diagnosis. This requires fol-lowing a systematic approach based on set radiographic guidelinesas (a) defining dysplasias involving the axial skeleton and furtherdelineating the anatomic areas of affection i.e. skull, mandible,

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spine ribs and pelvis, and (b) defining dysplasia involving theappendicular skeleton and further delineating the anatomic areasof affection i.e. proximal, middle and distal segments of the limbs.The geographic area of affection inside the bone segment involvedis then further identified i.e. epiphyseal, metaphyseal and diaphy-seal or a combination; (c) finally reporting abnormalities in bonedensity and configuration. The radiographic differential diagnosisof skeletal dysplasias that overlap with PSACH is presented usingclinical cases evaluated in our institution (Fig. 4A–G). We plan tosubject our patient to guided growth surgery in the near future,to address the valgus deformity of his knees. We will conduct reg-ular follow-up examinations for evidence of lower limb and spinedeformities, symptomatic joint hypermobility, degenerative jointdisease, and neurologic manifestations, particularly spinal cordcompression related to atlantoaxial instability.

3.1. Genetic profiling

Pseudoachondroplasia is inherited in an autosomal dominantmanner due to mutations in the COMP gene, though one case of avery rare autosomal recessive form has been documented. Whenneither parent of a proband with pseudoachondroplasia has clini-cal evidence of the disorder, it is likely that the proband has a denovo pathogenic mutation as seen in our patient [15,16]. Cartilage

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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. Lateralradiographs of the dorsolumbar spine (B) depicting oval shaped vertebrae with anterior beak originating from the central portion of vertebral body (arrows). Anteroposteriorradiographs of the dorsolumbar spine (C) demonstrating normal widening of the interpedicular distances caudally. In contrast, achondroplasic patients exhibit unchanged ornarrow interpedicular distance. This is an important distinguishing radiographic feature.

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oligomeric matrix protein (COMP) is an extracellular matrix pro-tein found primarily in cartilage and other musculoskeletal tissues.This gene provides instructions for making a protein that is essen-tial for the normal development of cartilage and for its conversionto bone [17]. Mutations in COMP gene result in protein misfoldingand intracellular retention inside the chondrocyte which leads toearly chondrocytes death and ultimately prevents normal bonegrowth causing short stature and bone abnormalities in pseudoa-chondroplasia [15]. Likewise the largest proportion of autosomaldominant MED (AD-MED) results from mutations in COMP gene;however, AD-MED is genetically heterogenous and can also resultfrom mutations in matrilin-3 (MATN3) and type IX collagen(COL9A1, COL9A2, and COL9A3). In contrast, autosomal recessiveMED appears to result exclusively from mutations in sulphatetransporter solute carrier family 26 (SLC26A2) [14,18–21]. Severalstudies have documented that meticulous evaluation of skeletal

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radiologic manifestations can help in prioritizing the genes to besequenced in the context of PSACH and the MED disease spectrum[14,18–20].

3.2. Conclusion

Our study findings affirm the conclusions of previous literaturereports that anthropometric measurements provide an objectivebasis for recognizing and classifying disproportionate growth andaid in differential diagnosis [11–13]. Accurate diagnosis remainslargely based on appropriate history taking, with the unique clini-cal and radiographic skeletal findings. Efficient and effective team-work between paediatrician, geneticist, radiologist and paediatricorthopaedic surgeon in the evaluation process of PSACH is para-mount to accurate diagnosis.

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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 flathorizontal acetabuli. Lateral radiographs of the dorsolumbar spine (B) depicting hypoplastic bullet shaped vertebrae with anterior wedging. Rickets. Radiographs of both legsof a child with healing rickets (C) depicting metaphyseal broadening, cupping and metaphyseal line of ossification (arrows), especially around the knee. Mark that epiphysealdensity 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 dorsolumbarspine (E) in a 7-year-old female child depicting various degrees of platyspondyly, anterior beaking mainly arising from inferior portion of vertebral body, dorsolumbarkyphosis, and broadened ribs especially anterior. Radiographs of her pelvis and both hips (F) depicting coxa valga shallow acetabuli and epiphyseal changes mimickingbilateral 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 vertebralwedging (black arrows), and anterior wedging (hollow white arrows).

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Conflict of interest

The authors report no conflict of interest concerning the mate-rials or methods used in this study or the findings specified in thispaper.

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