Objective-To determine if a relationship exists between the clinical features of Rett Syndrome, an X-linked dominant neurodevelopmental disorder, and specific mutations in MECP2.Method-Cross-sectional study of two hundred and forty-five girls and women with typical Rett Syndrome seen between 1990 and 2004 in tertiary academic out-patient specialty clinics and who had complete MECP2 mutation analysis. A structured clinical evaluation was completed for each participant. The results were grouped by MECP2 mutation and compared.Results-Participants with the R133C mutation are less severely affected than those with R168X or large DNA deletions (p<0.05). Likewise, individuals with the R168X mutation are more severely affected than those with R294X and late carboxy-terminal truncating mutations (p<0.05). Clinical differences are notable in ambulation, hand use, and language, (p<0.004) three cardinal features of Rett Syndrome. Individuals with R168X are less likely to walk (p=0.008), retain hand use (p=0.002), or use words (p=0.001). In contrast, those with carboxy-terminal truncations are more likely to walk (p=0.007) and use words (p<0.001). The R306C mutation, previously found to confer milder features, adversely affects only one clinical feature, language (p<0.05).Conclusions-Specific mutations in MECP2 confer different severity. These results allow the design of therapies targeted towards the amelioration of expected problems. Furthermore, the distinct effects of MECP2 mutations on clinical severity must be considered in clinical intervention trials.

In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays.

Normative body composition during the first 2 y of life was derived from a prospective study of 76 children. We present 1) fat free mass (FFM) and its components, and fat mass (FM), 2) incremental growth rates partitioned into chemical components, and 3) age-specific and gender-specific constants for converting chemical and physical components into FFM for children during the first 2 y of life. A multicomponent model based on measurements of total body water (TBW), total body potassium (TBK) and bone mineral content (BMC) was used to estimate FFM and FM at 0.5, 3, 6, 9, 12, 18, and 24 mo of age. TBW was determined by deuterium dilution, TBK by whole body counting, and BMC by dual energy x-ray absorptiometry. FFM was higher in boys than girls between 0.5-18 mo of age (p < or = 0.05). Percent FM increased on average from 13 to 31% between 0.5 and 3-6 mo, and then gradually declined. Percent FM was significantly higher in girls than in boys at 6 and 9 mo of age (p < or = 0.02). The components of FFM on a percentage basis changed with age (p = 0.001), but not gender. The protein content of FFM increased gradually with age, while TBW declined (p = 0.001). As a percentage of FFM, osseous mineral increased from 2.0 to 3.4% in boys and from 2.1 to 3.3% in girls between 0.5 and 24 mo (p = 0.001). Density and potassium content of FFM increased gradually with age (p = 0.001). These normative body composition data provide an updated reference upon which to assess normal growth and nutritional status of pediatric populations representative of mixed feeding groups during the first 2 y of life.

This study gives strong support to the view that in patients with RC defects, cardiomyopathy is more common than previously thought and tends to follow a different and more severe clinical course. Although with a greater frequency than previously reported, mitochondrial DNA mutations were found in a minority of patients, emphasizing that most mitochondrial disorders of childhood follow a Mendelian pattern of inheritance.

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