Creating a face shape and body stature model can be a tool for early diagnosis of rare disorders such as Morquio A and other mucopolysaccharidoses. The model in this study was constructed according to measurements and z-score estimates of the highest possible precision, thereby allowing the accurate rendering of both face and body. Mathematical modelling in science is primarily employed to simplify certain complex processes. Modelling allows the scale of the phenomenon to be changed, thus enhancing understanding. In the case of biology, modelling performs a particular role, enabling the separation of complicated relationships and processes. A good model can replace a series of individual measurements performed on a small number of parameters describing individual development. Creating a universal model of the body stature of MPS IVA is a challenging task because of the wide spectrum of disease severity. There is a scarcity of literature reporting detailed anthropometric data for children with MPS diseases [5, 6]. Constructing such a model requires measurement tools of maximum precision and monitoring of development parameters, specifically age ranges. This mix-longitudinal study gave the possibility of investigating the physical development of patients with MPS IVA. The results showed that anthropometric features of MPS IVA patients differed from the healthy population. Mean body length for boys in the studied MPS IVA group was statistically significantly greater, then the healthy population at the time of birth. This trend was corroborated in previous publications; it is also characteristic in other mucopolsaccharidoses including MPS I, II, and VI [17–19]. The pathomechanism of this phenomenon is still unclear. Following birth, children with MPS IVA grow slowly, and reach their final height at approximately 8 years. This corresponds to a -8 z-score for height in healthy peers [5]. In our study, patients stop growing on average at approximately 7.6 years. The mean z-score for body height was − 6.53, but for groups there was a difference between the oldest groups for boys and girls, with a mean z score for boys of -6.76 and for girls of -10.9. The reason for this difference was unknown, we could not rule out the influence of unknown external factors. Doherty describes a case of a patient who reached a maximum adult height of 86.4 cm; this coresponds to a -13 z-score compared to nationally published reference charts, and his phenotype was more severe than an average MPS IVA patient [20].
The study showed that differences in body proportion between healthy and affected children increased with age. Analysis of anthropometric measurements among MPS IVA patients allowed for distinction of features which deviated from the normal population. The thoracic spine from T1 to T12, as well as the lumbar region of the spine from L1 to L5, stops growing early, causing MPS IVA patients to have a short trunk [6]. The most common deformity for MPS IVA presents in the lower extremities of the knee and ankle valgus. The articular cartilage is abnormal and will quickly degenerate, leading to the build-up of early arthrosis, especially in the lower extremities. In this study, a significant reduction of body height was shown in all patients because of short trunk and crooked lower extremities [21]. The shoulders were narrow and the chest presented pectus carinatum deformities. This is a marked deformity of the anterior chest wall caused by rib overgrowth – compared to other parts of the body – which restricts the lungs [6]. Because of degenerative changing in body stature, MPS IVA may be misdiagnosed as spondyloepiphyseal dysplasia or other musculoskeletal disorders [22], however a typical characteristic for MPS IVA are hypermobile joints secondary to ligamentus laxity [23]. Individuals with MPS IVA are described as having large heads, in actual fact, the head is large in comparison to body height but normal for the patient’s age, because the frontal bone, parietal bone, occipital bone and mandible bone growing for a longer time in comparison with the body. This causes a prominent forehead and elongated head [20]. In our study, head and neck measurements were relatively long in comparison to body height. This is due to MPS IVA patients having shorter necks, as the cervical spine in the C1-C7 region stops growing earlier than the head [6]. Notwithstanding this, the head has a tendency towards vertical growth, leading to dolichocephalic facial shape [24].
Enzyme replacement therapy (ERT) with recombinant human GALNS (has been approved recently for Morquio A syndrome. Progressive nature of Morquio A syndrome, early diagnosis is critical to ensure rapid treatment and optimal patient outcomes [25]. The method used in this study could be used to construct models for other rare diseases with dysmorphic features, especially other mucopolysaccharidoses.
The study could have been improved. Morquio A disease is a rare disorder and we only had a limited data sample. For rare disease, it is difficult to collect enough data to make separate analyses for sex and age groups. Number of study group would required next 20 years to be sufficient. Also for analysis of natural history and body proportion we need a patients who are naïve to ERT, what will be difficult due to the availability of treatment. Therefore some alternatives must be found. In our study to construct universal model of body proportion for patients with MPS IVA, all measurements were standardized to age and gender. This procedure transforms two different variables (with incomparable measures) into one comparable statistical measure. In first analysis we pool all data together to show an universal model of body stature and face shape for individuals with MPS IVA. This has disadvantages - the image of the studied group may be imprecise, because of changes in body proportion increased with age. Therefore the second analysis for age groups and gender was performed. Our study has the mix-longitudinal character [26, 27] this method can be used when there is an insufficient number of subjects [5, 28] A great number of patients had problems with deformities of their lower extremities which, despite applied procedures, might have resulted in measurement errors. Nonetheless, although the modelling of the studied group may have been imperfect, the final model still demonstrated the main characteristics of MPS IVA.