Length, Weight and Head Circumference at Birth
Information on weight at birth was available for 47 females and 35 males. Information on length at birth was available for 47 females and 31 males. Information on head circumference at birth was available for 40 females and 26 males.
The average gestational age was 39 weeks, with a range between 32 and 42. Gestational age in MWS was completely comparable to that of the general population.
Weights at birth were found to be within the normal range in both males and females. The average weight in males was 3,288 g, with a range between 1,850 g and 4,500 g; the average weight in females was 3,340 g, with a range between 1,620 g and 4,060 g. The birth weight of all males was between the 2nd and 100th centiles for gestational age (mean 51st centile); the females’ birth weight was between the 3rd and 100th centiles (mean 54th centile).
Length at birth was within the normal range for the vast majority of patients, both males and females. The average birth length in males measured 50 cm, with a range between 43 and 56 cm (range 2nd to 99th centile, mean 44th centile). The average birth length in females was 49.1 cm, with a range between 41 and 54 cm (range <1st to 100th centile, mean 53rd centile).
Despite the fact that in both sexes the average head circumference at birth was within the normal range, most patients were under the 50th centile, with mean values at the 27th centile for males and 31st for females. In males, the mean was 33.2 cm, with a range between 28.5 and 36 cm (<1st to 96th centile); in females, the mean was 33.7 cm, with a range between 28.5 and 36 cm (<1st to 100th centile).
Length and height
The mean number of longitudinal measurements per patient in males was 9.56 (SD 5.51). For 45 patients we had at least 2 measurements, and for 40 patients we gathered more than 4 measurements.
The mean number of longitudinal measurements per patient in females was 11.00 (SD 7.11). For 53 patients we had at least 2 measurements, and for 48 patients we gathered more than 4 measurements.
Up to the age of 2 months, the length of both males and females was within, or just below, the normal range. Subsequently, height in males began to increase more slowly. A significant reduction in the slope of the growth curves was noted after 7 years of age, as the height of boys affected by MWS became even more distant from the reference curves of the general population (Fig.1 and Additional file 3 Fig. RD1).
Mean height for male patients at the age of 9 years was 121 cm (<3rd percentile, mean reference group at 50th percentile: 133 cm) and for female patients was 123.8 cm (3rd -5th percentile, mean reference group at 50th percentile: 130 cm).
In females, from 2 months of age, height had a slower increase as in males, and subsequently diverged even further from the reference curves of the general population. A significant reduction in the slope of the growth charts was noted after 11 years of age, much later than in males. At this age, females affected by MWS became noticeably distant from the reference curves of the general population, but were slightly less distant than males (Fig.2 and Additional file 4 Fig. RD2).
We were not able to extend the growth charts over the age of 16 years due to the limited availability of measurements after this age. Furthermore, it is not yet possible to calculate the final height because MWS has only relatively recently been described and the data on adolescent and young adult patients is still very limited.
Weight and Body mass index
The mean number of weight measurements per patient in males was 10.41 (SD 5.67). For 45 patients we had at least 2 measurements and for 41 patients we gathered more than 4 measurements.
The mean number of weight measurements per patient in females was 12.07 (SD 7.41). For 52 patients we had at least 2 measurements and for 50 patients we collected more than 4 measurements.
At age 0 to 36 months, compared to the reference group, the growth curves for weight were slightly lower than normal in both genders. Mean weight for male patients at age 5 years and 6 months was 16.800 kg (10th percentile, mean reference group at 50th percentile: 19.500 kg) and for female patients was 15.400 kg (10th percentile, mean reference group at 50th percentile: 19 kg).
After this age the growth charts flatten out considerably when compared to the normal reference group (Fig.3-4, Additional file 5 Fig.RD3, Additional file 6 Fig. RD4).
At the age of 16 years both male and female patients were considerably lighter (males: mean 48 kg 5th percentile, mean reference group at 50th percentile: 61 Kg; females: mean 39 kg <3rd percentile, mean reference group at 50th percentile: 54 Kg). Most patients were of slender build, with normal body proportions.
BMI in the age range 0 to 6 years was slightly lower with respect to the normal reference group. Mean BMI for male patients at 6 years of age was 15 kg/m2 (mean reference group: 15.4 kg/m2) and for female patients was 14.9 kg/m2 (mean reference group: 15.3 kg/m2). Thereafter, between the ages of 6 and 16 years, the curve for BMI flattened out significantly in both genders, but in males the shift of the curve towards lower values was more pronounced and occurred earlier, already at the age of 7 years, while in females it became significant after the age of 9 years (Fig.5).
BMI of male patients aged 16 years (mean 17.2 kg/m2) was significantly lower compared to the reference group (mean 20.5 kg/m2). BMI of female patients aged 16 years (mean 17.1 kg/m2), was significantly lower compared to the reference group (mean 20.5 kg/m2).
Head circumference
The mean number of head circumference measurements per patient in males was 6.54 (SD 4.79). For 39 patients we had at least 2 measurements, and for 31 patients we collected more than 4 measurements.
The mean number of head circumference measurements per patient in females was 8.54 (SD 6.23). For 51 patients we had at least 2 measurements, and for 41 patients we collected more than 4 measurements.
At birth, head circumference differed only slightly from the reference group in both genders. Indeed, during the first months of life, most measurements were between the 3rd and the 25th percentile of the curves for healthy controls. This changed significantly after 1 year of age: MWS patients had a significantly smaller head circumference between the ages of 1 and 2 years. Between the ages of 2 and 3 years the curves flattened out even more and the head circumference was significantly smaller compared to healthy controls.
Mean head circumference for male patients at age 3 years was 47 cm (5th percentile, <-2SD, mean reference group at 50th percentile: 50 cm) and for female patients was 46 cm (5th percentile, -2SD, mean reference group at 50th percentile: 49 cm) (Fig. 6-7 and Additional file 7 Fig. RD5 Additional file 8 Fig.RD6).
It should be noted that not all children were microcephalic (at least 2 SD below the mean).
The curves for males and females continued to flatten out in the following age ranges, up to the age of 16 years. Adolescent male patients at the age of 16 years had a mean head circumference of 52 cm (<3rd percentile <-2 SD), the females had a mean head circumference of 49.8 cm (<3rd percentile <-2SD) (Fig.8-9).