Absence Of Growth Retardation Research Articles

Markers of enteral adaptation in pediatric short bowel syndrome.

The aim of this study was to ascertain if prospective determination of specific gut hormones and growth factors could predict bowel adaptation in children with short bowel syndrome (SBS). We studied independence from parenteral nutrition (PN) as the short-term result and discontinuation of enteral nutrition (EN) as the long-term result from a retrospective chart review of seven patients with SBS, who were managed in the absence of growth retardation. The correlation between increased number of enteral feeds or enteral nutrients and fasting serum gastrin, glucagon-like peptide 2 (GLP-2), citrulline, and D-amino acid oxidase (DAO) activity was analyzed. Five patients were weaned from PN, and two from EN. Fasting serum gastrin was significantly higher and serum GLP-2 lower in the PN-dependent patients than in the patients weaned from EN. The upper limit of fasting serum gastrin for PN independence and for EN independence was 300 and 200 pg/mL, respectively. The lower limit of fasting serum citrulline for PN independence was 15 μmol/L. The relationship between serum citrulline and DAO and the course of bowel adaptation, however, was poor. Serum citrulline is a predictor of PN independence in children with SBS. Fasting serum gastrin and GLP-2 are indicators for adaptation of the residual intestine, but this was a small study and further larger prospective trials are required to confirm these results.

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes.

Cushing's Syndrome Due to a Non-Adrenal Ectopic Adrenocorticotropin-Secreting Ewing's Sarcoma in a Child

Ectopic ACTH syndrome (EAS) is extremely rare in the pediatric age group. Sarcomatous tumors causing EAS are even rarer. We report a 9 year-old girl presenting with Cushing's syndrome caused by ectopic ACTH production by a Ewing's sarcoma. This case illustrates that rapid appearance of Cushingoid symptoms, absence of growth retardation and the presence of hypokalemia are suggestive clues for ectopic ACTH production as the source of Cushing's syndrome.

O.430 Seven points to enhance the aesthetic results of cleft lip and nose reconstruction

Purpose: The controversy regarding the timing of repair of the deformities associated with cleft lip and palate still exists. The goal of this article is to present a versatile, universal philosophy of management of these deformities involving early repair. Patients and Methods: Over 20 years, 2,698 new patients with cleft lip and palate deformities were treated. These included 1,298 unilateral and 320 bilateral cleft lip and palate patients. The remaining patients (1,018) had isolated palatal clefts. All patients were operated according to the same protocol and the same surgical procedure. The treatment philosophy was based on early, wide myoperiosteal-periosteo-sutural reconstruction by a modified Delaire functional cheilorhinoplasty and alveolar gingivoperiosteoplasty at 3 months, followed by soft and hard functional palatoplasty at 9 months. Results: All patients were followed longitudinally and retrospectively. The parameters investigated were facial symmetry, presence or absence of growth retardation, and oropharyngeal and nasal function. The parameters studied indicated that when this treatment schedule was followed and the procedures were performed on time and according to the protocol, there was minimal growth retardation of the maxilla. When early gingivoperiosteoplasty was performed in 25% of the patients there was a sufficient amount of alveolar bone for eruption of the primary and permanent dentition. This negated the need for secondary alveolar bone grafting. The development of the upper lip was harmonious, and usually no further corrective procedures were necessary. The nose was usually well developed and functionally normal. Conclusion: Optimal rehabilitation of the patients was achieved by following the principles and treatment strategies described. If the treatment principles are not incorporated in the functional repair (ie, joining of the primary and the secondary growth centers during corrective procedures), compromised results are to be expected. © 2001 American Association of Oral and Maxillofacial Surgeons

Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency

We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A’s negligible PC1 activity, some mature ACTH and glucagon-like peptide 17-36amide were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species.

Comprehensive management of cleft lip and palate deformities

Purpose: The controversy regarding the timing of repair of the deformities associated with cleft lip and palate still exists. The goal of this article is to present a versatile, universal philosophy of management of these deformities involving early repair. Patients and Methods: Over 20 years, 2,698 new patients with cleft lip and palate deformities were treated. These included 1,298 unilateral and 320 bilateral cleft lip and palate patients. The remaining patients (1,018) had isolated palatal clefts. All patients were operated according to the same protocol and the same surgical procedure. The treatment philosophy was based on early, wide myoperiosteal-periosteo-sutural reconstruction by a modified Delaire functional cheilorhinoplasty and alveolar gingivoperiosteoplasty at 3 months, followed by soft and hard functional palatoplasty at 9 months. Results: All patients were followed longitudinally and retrospectively. The parameters investigated were facial symmetry, presence or absence of growth retardation, and oropharyngeal and nasal function. The parameters studied indicated that when this treatment schedule was followed and the procedures were performed on time and according to the protocol, there was minimal growth retardation of the maxilla. When early gingivoperiosteoplasty was performed in 25% of the patients there was a sufficient amount of alveolar bone for eruption of the primary and permanent dentition. This negated the need for secondary alveolar bone grafting. The development of the upper lip was harmonious, and usually no further corrective procedures were necessary. The nose was usually well developed and functionally normal. Conclusion: Optimal rehabilitation of the patients was achieved by following the principles and treatment strategies described. If the treatment principles are not incorporated in the functional repair (ie, joining of the primary and the secondary growth centers during corrective procedures), compromised results are to be expected. © 2001 American Association of Oral and Maxillofacial Surgeons

Absence of Growth Retardation in Children With Perennial Allergic Rhinitis After One Year of Treatment With Mometasone Furoate Aqueous Nasal Spray

Intranasal corticosteroids are used widely for the treatment of allergic rhinitis because they are effective and well tolerated. However, their potential to suppress growth of pediatric subjects with allergic rhinitis continues to be a concern, particularly in light of reports of growth suppression after treatment with intranasal beclomethasone dipropionate or intranasal budesonide (see the article by Skoner et al in this month's issue). A 1-year study of prepubertal patients between 3 and 9 years of age with perennial allergic rhinitis was conducted to assess the effects on growth of mometasone furoate aqueous nasal spray (MFNS), a new once-daily (QD) intranasal corticosteroid with negligible bioavailability. This was a randomized, placebo-controlled, double-blind, multicenter study. Ninety-eight subjects were randomized to treatment with either MFNS 100 microg QD or placebo for 1 year. Each subject's height was required to be between the 5th and 95th percentile at baseline, and skeletal age at screening was required to be within 2 years of chronological age, as determined by left wrist x-rays. Washout periods for medications that affect either childhood growth or allergic rhinitis symptoms were established based on estimated period of effect, and these medications were prohibited during the study. However, short courses of either oral prednisone lasting no longer than 7 days or low-potency topical dermatologic corticosteroids lasting no longer than 10 days were permitted if necessary. Height was measured with a calibrated stadiometer at baseline and at 4, 8, 12, 26, 39, and 52 weeks, and the primary safety variable was the change in standing height. The rate of growth was also calculated for each subject as the slope (linear regression) of the change in height from baseline using data from all visits of subjects who had at least 2 visits. Hypothalamic-pituitary-adrenocortical- (HPA)-axis function was assessed via cosyntropin stimulation testing at baseline and at 26 and 52 weeks. All analyses were based on all randomized subjects (intent-to-treat principle). The change from baseline in standing height was analyzed by a 2-way analysis of variance that extracted sources of variation attributable to treatment, center, and treatment-by-center interaction. Demographic characteristics were similar at baseline. Eighty-two subjects completed the study (42 in the MFNS group and 40 in the placebo group), and 93% of subjects achieved at least 80% compliance with therapy. After 1 year of treatment, no suppression of growth was seen in subjects treated with MFNS, and mean standing heights were similar for both treatment groups at all time points. For the primary safety variable (change in height from baseline), both treatment groups were similar at all time points except for weeks 8 and 52. Subjects treated with MFNS had a slightly greater mean increase in height than subjects treated with placebo at these time points: the change in height was 6.95 cm versus 6.35 cm at the 1-year time point. However, the rate of growth (.018 cm/day) averaged for all time points over the course of the study was similar for both treatment groups. Additional analyses found that MFNS did not retard growth in any sex or age subgroup of subjects. The use of exogenous corticosteroids other than the study drug was also similar among the 2 treatment groups. Results from cosyntropin stimulation testing confirmed the absence of systemic effects of MFNS. The change from baseline in the difference between prestimulation and poststimulation levels was similar for both treatment groups after 1 year of treatment, with no evidence of HPA-axis suppression in MFNS-treated subjects at any time point. Incidences of treatment-related adverse events were similar for both treatment groups, with 16% of MFNS-treated subjects reporting adverse events, compared with 22% of placebo-treated subjects. (ABSTRACT TRUNCATED)