How to Cite this Article: Aglan MS, Zaki ME, Hosny L, El-Houssini R, Oteify G, Temtamy SA. 2012. Anthropometric measurements in Egyptian patients with osteogenesis imperfecta. Am J Med Genet Part A 158A: 2714–2718.
Osteogenesis imperfecta (OI) is a bone-related genetic disorder characterized by low bone mass and bone fragility that is clinically and genetically heterogeneous [Sillence et al., 1979].
Most cases of OI are caused by mutations in the type I procollagen genes, COL1A1 and COL1A2, and follow an autosomal-dominant pattern of inheritance [Byers and Steiner, 1992]. In a minority of cases with severe manifestations, autosomal recessive inheritance was proposed and homozygous mutations in collagen I related genes were recently identified [Barnes et al., 2006; Morello et al., 2006; Cabral et al., 2007; Drögemüller et al., 2009; van Dijk et al., 2009; Alanay et al., 2010; Christiansen et al., 2010; Lapunzina et al., 2010; Becker et al., 2011; Martínez-Glez et al., 2012].
Clinical characteristics of OI are variable, and even different members of the same family may present with a dissimilar degree of severity [Plotkin, 2004]. Most patients have growth retardation especially types III and IV [Lund et al., 1999].
This study aims at the evaluation of anthropometry in Egyptian children with OI and determines variability among OI types classified according to Sillence et al. .
PATIENTS AND METHODS
The study included 124 patients with OI. All were recruited from the limb malformations and skeletal dysplasia Clinic (LMSDC), Medical Services Unit, NRC. Patients were evaluated clinically and radiologically. Accordingly, they were characterized into Sillence types I, II, and IV. One patient was consistent with type II and was excluded from the study. Ethical approval and appropriate informed consent was obtained from all subjects included in this study or their parents.
Five anthropometric measurements were taken for each patient before the initiation of biphosphonate treatment including: length or standing height, weight, head circumference, arm span, and sitting height. Measurements and instruments followed the recommendations of the international biological program (IBP) [Hiernaux and Tanner, 1969] and Hall et al. :
Length (Lt) was measured from birth up to 24 months of age or if the patient was unable to stand, using a measuring table with a perpendicular piece and a movable one. The patient lies supine with the knee held flat.
Standing height (Ht) was measured by a stadiometer. The patient stood straight so that the heels, buttocks, and shoulders were in contact with the wall. The head was positioned in the Frankfort-plane and the medial malleoli were touching each other. In cases of leg length discrepancy or contractures, the longest leg was used in all measurements. Length and height measurements in children with bone deformities are difficult to perform. Therefore, all measurements were performed by personnel experienced in dealing with subjects with deforming bone disorders.
Weight (Wt) was measured by a digital weighting machine. The patient was unclothed, or with light under wear.
Head circumference (HC) was measured by stainless steel non-stretchable tape from the occiput passing above but not including the brow ridge.
Sitting height (Sitt. Ht) was measured by an anthropometer with the patient's back stretched up straight while sitting on a table. The head was positioned in the Frankfort-plane.
Arm span (AS) a non-stretchable tape was used to measure the distance between the tips of the middle fingers of both hands with the arms outstretched sideways horizontally from the body.
Three indices were calculated for each patient: body mass index (BMI; Wt (kg)/Ht2 (m)], relative head circumference (RHC; HC/Ht × 100) and relative arm span (RAS; AS/Ht].
Anthropometric measurements and indices were expressed as standard deviation scores (SDS) for age and sex specific values, using the general formula, SDS = (X − Xi)/Sdi, where X is the individual patient value; Xi is the mean value for the normal reference Egyptian population; and Sdi is the standard deviation from normal value. Growth evaluation was based on the Egyptian Growth Reference Data [Ghalli et al., 2008]. All results were expressed as mean ± SD.
The arithmetic means, standard deviations, and the ranges were estimated [Dixon and Massey, 1983]. SDS values below and above the boundary of 2.5 were considered abnormal [UnderWood and Vanwyk, 1981; Tanner, 1984]. Comparison between different OI types was carried out using one-way analysis of variance (ANOVA) between groups and post hoc analysis Bonferroni test, was used for multiple comparisons. P-value was considered significant if ≤0.05 and highly significant if ≤0.005. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS version 16).
This study included 124 patients with OI (55 males and 69 females). They were classified into Sillence types OI-I (N = 16), OI-III (N = 86), and OI-IV (N = 22). Characteristics of the studied patients are shown in Table I.
Table I. Characteristics of the Studied Patients
Age at presentation (years) mean (range)
Table II presents the mean SDS values, standard deviation (SD) and results of ANOVA of the studied anthropometric parameters in different OI types.
Table II. Mean SDS Values, Standard Deviation (SD), Results of Analysis of Variance (ANOVA) of the Studied Anthropometric Parameters in Different OI Types
Standard deviation (SD)
ANOVA between groups (P-value)
Ht, height; Wt, weight; HC, head circumference; Sit. Ht, sitting height; BMI, body mass index; RAS, relative arm span; SDS, standard deviation score.
Mean length/height SDS values of OI-III and IV were below −2.5 SDS (−4.4 and −3.1, respectively). Results of ANOVA between groups showed a highly significant difference in height between OI types (P-value = 0.0001). A significant difference was present between OI-I and both OI-III and OI-IV (P = 0.001 and 0.013, respectively) and the result was adjusted for multiple comparisons. No significant difference was present between mean Ht SDS values in OI-III and OI-IV. Figure 1 shows height SDS against age for patients with Sillence types I, III, and IV OI.
Mean sitting height SDS in both OI-III and IV was decreased (−4.4 and −3.4 SDS) compared to OI-I (−1.5). ANOVA revealed significant difference between OI types (P-value = 0.05). A significant difference was detected between OI-I and OI-III only (0.046) and the result was adjusted for multiple comparisons. No significant difference was present between OI-III and OI-IV.
An increase in mean relative arm span SDS was found in OI-III only (106.4) compared to OI-I (97.7), and OI-IV (89.7). However, ANOVA showed no significant difference in relative arm span between OI types.
Mean weight SDS for patients with OI-III was significantly decreased (−2.6 SDS) compared to OI-I and OI-IV (0.2 and −1.2, respectively). ANOVA showed a highly significant difference between OI types (P-value = 0.0001). Post hoc test revealed a highly significant difference between OI-I and OI-III only (P = 0.0001). No significant difference was present between OI-III and OI-IV. Figure 2 shows weight SDS against age for patients with Sillence types I, III, and IV OI.
Body mass index lied within the normal ranges in all OI types. ANOVA gave no significant difference in these parameters between groups (P = 1.0).
In different OI types, mean SDS of head circumference was within normal limits. However, ANOVA showed a highly significant difference between OI types (P-value = 0.0001). A significant difference between OI-I and both OI-III and OI-IV (P = 0.0001) was present and the result was adjusted for multiple comparisons. No significant difference was present between OI-III and OI-IV (P = 0.27).
Mean SDS of RHC was increased in OI-III (6.25) and OI-IV (3.16) compared to OI-I (1.00). ANOVA gave a highly significant difference between OI types (P-value = 0.001). However, a highly significant difference was detected between OI-I and OI-III only (P = 0.0001) and the result was adjusted for multiple comparisons. No significant difference was present between OI-III and OI-IV. Figure 3 shows relative head circumference SDS against age for patients with Sillence types I, III, and IV OI.
Comparison between male and female OI patients showed no significant difference in any of the studied anthropometric parameters in different types.
This study included 124 patients with OI. Male to female ratio was 55/69 with a slight female predominance in agreement with Goldman et al.  and El-Houssini  who reported that the disease occurs in all races with a slight female predominance.
Several classification systems were proposed for cases with OI [Falvo et al., 1974; Bauze et al., 1975; Sillence et al., 1979; Hanscom et al., 1992; Plotkin, 2004]. According to the latest nosology and classification of genetic skeletal disorders, the authors agreed upon retaining the Sillence classification as the prototypic and universally accepted way to classify the degree of severity [Warman et al., 2011]. In this study we classified our patients according to Sillence et al.  into 3 types (I, III,and IV). Most patients belonged to type III OI.
Although growth deficiency is a key feature of severe OI and a frequent feature of mild to moderate forms of the disease [National Institutes of Health Clinical Center, 2007], it was difficult to find available literature that have included systematic anthropometric studies apart from that reported by Lund et al.  and El-Houssini . Regarding our results of length and standing height in OI patients, we were in agreement with Lund et al. , Zeitlin et al. , and El-Houssini  who found that many patients with OI-I and few with OI-IV had a standing height within the reference interval in contrast to those with OI-III.
The cause of short stature in OI patients is unknown; it may be due to fractures and deformities. Also, it may be due to the unresponsiveness of osteoblasts to normal growth factors. Collagen I, which is reduced or defective in OI patients is necessary for the expression of the osteoblast phenotype and its ability to respond to various growth factors. A defective osteoblastic/bone matrix feedback on the growth hormone IGF1 axis has been suggested [Marini et al., 1993a, b]. Lund et al.  studied serum concentrations of IGF-I and IGFBP-3 in different OI types and they were within the age specific reference intervals in almost all patients. However, concentrations were significantly lower in OI type III/IV than in OI-I.
A recent study in 161 OI patients who had glycine mutations in COL1A1 and in COL1A2 led to similar average height z-scores [Rauche et al., 2010a]. An inverse relationship was found between the height and the location of the mutation in the triple helical domain of the alpha 2 chain [Ben Amor et al., 2011]. As reported by Rauche et al. [2010a] height is not only affected by the location of the glycine mutation but also by the specific substituting amino acid. The authors found that serine substitutions lead to a shorter average stature when they affect the alpha 1 chain while patients with arginine mutations on average had less severe short stature and those with aspartate substitutions in the alpha 2 chain lead to a severe short stature. Other amino acid substitutions in either chain were not enough for statistical analysis. In another genotype–phenotype study of 192 OI patients, Rauche et al. [2010b] noted that patients with haploinsufficiency mutations on average were taller than patients with helical mutations in the alpha 1 or alpha 2 chains.
To describe the type of short stature in OI, unlike the results reported by Lund et al.  but in agreement with El-Houssini , we did not find a significant difference in mean relative arm span between the different groups. However, measurements of sitting height were below normal in few patients with OI-I and many patients with OI-III and IV with a significant difference between OI-I compared to both OI-III and IV indicating that short stature in types III/IV is mainly caused by reduction in truncal height, a finding that was also reported by Lund et al.  and El-Houssini . This can be attributed to platyspondyly, which is more common in OI types III and IV. Although biosynthetic effect is important for the development of platyspondyly and short trunk in OI, it is clear from our results that biomechanical abnormalities in more severe cases is of greater importance.
In agreement with El-Houssini , the present study showed that mean weight SDS values for all patients lied within the normal range. However, underweight was detected in many patients with OI-III. Mean SDS of BMI for all patients was normal with no significant difference between OI groups.
Relative macrocephaly was found in the studied patients with OI-III and IV but not in OI-I. The increased values in types III and IV are due to height reduction. Lund et al.  found a disproportion between head size and height in OI patients. They noticed an increase in head circumference (above +2.0 SDS) in 1/3 of the studied OI patients. However, they found no significant difference in head circumference between any of the OI groups. By subtracting standing height SDS from head circumference SDS, the authors reported values in all OI patients with more positive scores in types III and IV compared to patients with type I.
Using anthropometry, this study was able to quantitatively assess the body physique in OI in general and the variability among different types. Genotype–phenotype correlations in OI patients regarding anthropometric criteria need more studies.