Evolution of body mass index in children with type 1 diabetes mellitus.

The prevalence of childhood overweight and obesity has risen during the last 30 years, not only in children with type 2 diabetes, but also those with type 1 (T1D) and this is linked with an increased cardiovascular risk. A better understanding of weight patterns in the years after diagnosis of T1D is important to identify those children with a risk for excess weight gain and strategies to decrease this. We retrospectively analyzed data of all children with T1D followed at the department of Pediatric Endocrinology Leuven and diagnosed between 1991 and 2015. Data as age, sex, BMI, and Tanner score were extracted in 390 subjects. Standardized BMI (BMI SDS) in this study group using all data was 0.26. An increase in BMI SDS was seen as a function of time since diagnosis and age, both being independent predictors. Data comparison showed a significant stronger relation between BMI SDS and both time since diagnosis and age in girls. Children diagnosed after puberty showed a higher increase in BMI SDS.Conclusion: These longitudinal data suggest an important increase in BMI in children with T1D, both as a function of time since diagnosis and age, especially in girls. What is Known: • The prevalence of childhood overweight and obesity is risen during the last 30 years, in children with type 2 diabetes, but also those with type 1 diabetes. What is New: • Our study demonstrates with longitudinal data an increase in BMI in children with type 1 diabetes, especially girls. The increase in BMI SDS is seen as a function of time since diagnosis and age, both being independent predictors. Given the increased risk of metabolic syndrome and other complications in overweight children, special attention is needed to prevent this evolution.

Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies.

BACKGROUND: Biologicals targeting the interleukin (IL)-1ß or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA. METHODS AND RESULTS: We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 µg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain. CONCLUSION: A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently - albeit late - to a normal adult stature.

Expanding the CHARGE Geno-Phenotype: A Girl with Novel CHD7 Deletion, Hypogonadotropic Hypogonadism, and Agenesis of Uterus and Ovaries.

BACKGROUND: CHARGE syndrome is a variable entity. Clinical diagnosis is based on the Blake-Verloes criteria and can be confirmed by identifying a mutation or deletion in the CHD7 gene. Hypoplasia of the male genitalia and lack or incomplete secondary sexual development in both sexes is a common feature, and is most often attributable to hypogonadotropic hypogonadism which is described in >80% of the CHARGE patients. Other genital anomalies in CHARGE patients are rare. METHODS AND RESULTS: We describe the case of a girl with a novel heterozygous deletion in exon 15 of the CHD7 gene and combined agenesis of uterus and ovaries, besides gonadotropin deficiency, thus expanding the geno-phenotype of CHARGE syndrome. CONCLUSION: In case of persistent primary amenorrhea, despite estrogen replacement, this unusual combination should be considered in girls with CHARGE syndrome.

Short Stature in KBG Syndrome: First Responses to Growth Hormone Treatment.

BACKGROUND: KBG syndrome is a rare disorder characterized by intellectual disability and associated with macrodontia of the upper central incisors, specific craniofacial findings, short stature and skeletal anomalies. Genetic corroboration of a clinical diagnosis has been possible since 2011, upon identification of heterozygous mutations in or a deletion of the ANKRD11 gene. METHODS: We summarized the height data of 14 adults and 18 children (age range 2-16 years) with a genetically confirmed diagnosis of KBG syndrome. Two of these children were treated with growth hormones. RESULTS: Stature below the 3rd centile or -1.88 standard deviation score (SDS) was observed in 72% of KBG children and in 57% of KBG adults. Height below -2.50 SDS was observed in 62% of KBG children and in 36% of KBG adults. The mean SDS of height in KBG children was -2.56 and in KBG adults -2.17. Two KBG children on growth hormone therapy increased their height by 0.6 and 1 SDS within 1 year, respectively. The former also received a gonadotropin-releasing hormone agonist due to medical necessity. CONCLUSION: Short stature is prevalent in KBG syndrome, and spontaneous catch-up growth beyond childhood appears limited. Growth hormone intervention in short KBG children is perceived as promising.

Congenital nystagmus and central hypothyroidism.

We observed a male newborn with bilateral nystagmus and central hypothyroidism without hypoprolactinemia due to a deletion of chromosome band Xq26.1q26.2, containing FRMD7 and IGSF1. These two loss-of function mutations are known to cause, respectively, congenital nystagmus and the ensemble of central hypothyroidism, hypoprolactinemia and testicular enlargement. These latter two features may not yet be present in early life.