Short stature, unusual face, delta phalanx, and abnormal vertebrae and ribs in a girl born to half-siblings.

Delta phalanx is a rare abnormality typically associated with additional features. We describe a patient with a phenotype resembling Catel-Manzke syndrome, but with delta phalanx and abnormal vertebrae and ribs. The patient was the only child of half siblings born with a marked prenatal growth deficiency. At 10 years of age, she had a short stature, long face, long and tubular nose with small alae nasi, high palate, short and broad thorax, and short index fingers with radial deviation. There were hyperpigmentations following Blaschko's lines. Radiology showed a proximal delta phalanx in the index finger of hands, abnormal vertebrae, and fused and small ribs. GTG-Banding karyotype and microarray analysis yielded normal results. Exome sequencing identified 25 genes that harbored homozygous variants, but none of these is assumed to be a good candidate to explain (part of) the phenotype. The here described patient may have a new condition, possibly following an autosomal recessive pattern of inheritance, although due to the high degree of consanguinity a compound etiology of the phenotype by variants in various genes may be present as well.

Síndrome de Ellis Van Creveld: caso clínico / Ellis Van Creveld syndrome: case report

El Síndrome de Ellis Van Creveld es poco frecuente, hereditario de carácter autosómico recesivo no habiendo predilección por sexo. Se caracteriza por acortamiento acromesomélico, polidactilia postaxial bilateral de manos, condrodisplasia de huesos largos y displasia ectodérmica de uñas y dientes. El conocimiento de la misma es imperativo para un diagnóstico temprano y manejo multidisciplinario oportuno que permita una mejor calidad de vida de estos pacientes.

The Ellis Van Creveld syndrome is rare, hereditary autosomal recessive, without no sex predilection. It is characterized by short-limbed dwarfism, bilateral postaxial hand polydactyl, chondrodysplasia of long bones and ectodermic dysplasia affecting fingernails and teeth. The knowledge of it is essential for early diagnosis and appropriate multidisciplinary management that allows a better quality of life for these patients.

Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test.

OBJECTIVE: To test the efficacy of the low-dose glucagon test in assessing adrenal gland function. STUDY DESIGN: Subcutaneous glucagon was used to assess the hypothalamo-pituitary-adrenal gland (HPA) axis in 215 healthy children. Concordance of this test with the low-dose intravenous ACTH test was established for 42 children. Glucagon testing was conducted for 150 minutes after subcutaneous glucagon administration and for 30 minutes after 1 microg intravenous ACTH. RESULTS: Mean peak serum cortisol concentrations were 22.4 +/- 0.6 microg/dL (SEM) after subcutaneous glucagon and 20.0 +/- 0.6 microg/dL after intravenous ACTH. Specificity of 95% was found at peak cortisol concentrations of 9.5 and 12.5 microg/dL for the glucagon and ACTH tests, respectively. Concordance between the glucagon and ACTH tests was 90.5%. CONCLUSIONS: The glucagon test was found to be as good a test of the HPA axis as the ACTH test and had a 90.5% concordance with it. The ease of performing the glucagon test, namely, obtaining a single sample of blood 150 minutes after the subcutaneous administration of glucagon, makes it a useful method of assessing the HPA axis in primary care settings.

Bone status in an animal model of chronic sub-optimal nutrition: a morphometric, densitometric and mechanical study.

In children, inappropriate eating habits can induce a disease known as nutritional dwarfing (ND). Due to the link between nutritional condition and bone growth, the effects induced by a 20 % reduction of food intake on bone competence were assessed in an animal model of ND. Bone status during catch-up growth was also analysed. Male Wistar rats were divided into control (C) and ND groups. C rats were fed ad libitum. ND received 80 % of the diet consumed by C for 4 weeks (T4); thereafter, they were fed ad libitum for 8 weeks. Results, expressed as mean (SEM) for ND v. C, were as follows. At T4, body weight (g) and length (cm) and femur weight (g) and length (mm) were 97.35 (SEM 5.89) v. 199.07 (SEM 9.24), 16.91 (SEM 0.41) v. 20.26 (SEM 0.31), 0.30 (SEM 0.01) v. 0.46 (SEM 0.01) and 23.09 (SEM 0.29) v. 26.98 (SEM 0.26), respectively (P<0.001); bone mineral content (g) and density (g/cm(2)) were 0.014 (SEM 0.002) v. 0.030 (SEM 0.002) and 0.061 (SEM 0.004) v. 0.080 (SEM 0.003), respectively (P<0.001); load-bearing capacity (N), yielding load (N) and elastic stiffness (N/mm) were 25.06 (SEM 1.24) v. 50.34 (SEM 2.94), 23.72 (SEM 1.02) v. 46.97 (SEM 1.75) and 65.98 (SEM 4.42) v. 115.07 (SEM 3.85), respectively (P<0.001); cross-sectional area (mm(2)) and moment of inertia (mm(4)) were 2.86 (SEM 0.19) v. 4.54 (SEM 0.17) and 1.27 (SEM 0.08) v. 3.03 (SEM 0.16), respectively (P<0.001). Significant effects were not evident in material properties. Parameters assessed normalized during re-feeding. These results suggest that the impaired mechanical femur competence in ND rats could be due to an altered bone mass and architectural distribution rather than to intrinsic quality. Re-feeding caused a reversal of the effects of food restriction on growth and bone parameters in ND rats.

Bone growth in nonorganic nutritional dwarfing rats.

Since no data are available to characterize mandibular growth in nonorganic nutritional dwarfing (ND), the purpose of the present study was to describe the effects of a diet on mandible and femur growth in a nutritional dwarfish animal model. Male Wistar rats were divided into two groups of 10 animals each: Control (C) and Experimental (E80: diet-restricted group). C rats were fed a standard diet ad libitum. E80 rats received 80% of the amount of standard diet eaten by group C. Food intake and body weight (Wt) and length (Lt) were recorded periodically. Growth data (Wt and Lt) were expressed as a Z-score of weight-for-length (WLZ) ratio, an index of body size. Five animals of each group were selected at random at 4 and 8 weeks and sacrificed. Additionally at t = 0, 5 animals were sacrificed for baseline measurements. Mandibular growth was estimated directly on the right mandible by measuring ten dimensions. Femur growth was estimated from Wt and Lt measurements of the bone. Mandibular weight, area, length and height were negatively affected by dietary restriction during the first 4 weeks of the experimental period. Mandibular growth ceased after this point. Dimensions corresponding to the alveolar unit did not change with time. However, all other dimensions were negatively influenced but not to the same extent. Femur rather than mandibular weight was severely affected. Therefore, the negative effects of the nutritional stress that occurs after weaning would be stronger for the femur, than for the mandible. Femur length was also negatively affected by suboptimal nutrition. In summary, the results of the present study showed that mandible and femur growth respond differently to mild chronic food restriction. These observations could be explained in terms of the different critical bone growth periods and of the time at which nutritional stress was imposed.

Costello syndrome: phenotype, natural history, differential diagnosis, and possible cause.

We describe 8 patients affected with Costello syndrome including an affected sib pair and review the literature on 29 previously reported cases. We emphasize an association with advanced parental age, which is consistent with autosomal dominant inheritance with germline mosaicism. The pathogenesis appears to involve metabolic dysfunction, with growth disturbance, storage disorder appearance, acanthosis nigricans, hypertrophic cardiomyopathy, and occasional abnormalities of glucose metabolism. Although the cause is currently unknown, Costello syndrome is interesting because of a potential genetic-metabolic etiology.

El síndrome de la "Isla de la Fantasía". Individualización de una nueva osteocondrodisplasia probablemente autosómica dominante / \"Fantasy Island\" a new osteochondrodysplasia which is probably autosomal dominant

Se estudiaron dos pacientes no emparentados, un varón adulto y una niña, sin antecedentes de consanguinidad, quienes clínicamente presentaron enanismo, facies peculiar, hendiduras mogoloides, cejas y pestañas abundantes, voz ronca, además de manos y pies pequeños. En los estudios radiológicos presentaron braquimetacarpalia, braquimetatarsalia, braquifalangia en dedos de manos y pies, huesos largos ensanchados y acortados con morfología aparentemente normal, pelvis hipoplásica y alteraciones en la forma de los cuerpos vertebrales. La concordancia clínica y radiológica, así como el diagnóstico diferencial, principalmente con la displasia acromícrica, permiten caracterizar una osteocondrodisplasia producida probablemente por una mutación autosómica dominante

Regulation of serum insulin-like growth factors and their binding proteins in Ecuadorean patients with growth hormone receptor dysfunction (growth hormone insensitivity).

Regulation of serum insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and growth hormone (GH) binding protein (GHBP) has been investigated in Ecuadorean patients with GH receptor dysfunction (GHRD) and in their heterozygous relatives (parents). Serum IGF-I and IGF-II levels were measured by radioimmunoassay (RIA). IGFBPs were identified by Western ligand blotting of serum samples, following separation by sodium dodecyl sulphate polyacrylamide gel electrophoresis, and relative quantification was performed with a scanning laser densitometer. Serum GHBP levels were measured with a ligand-mediated immunofunctional assay (LIFA) using a monoclonal antibody raised against the GHBP. These values were then compared with values obtained from normal, sex-matched Ecuadorean controls. Serum IGF-I, IGF-II, IGFBP-3 and GHBP concentrations were markedly reduced and serum IGFBP-2 values increased in the patients with GHRD. Serum IGF-I and IGF-II values were positively correlated in the patients with GHRD, but were not related to the age of the patient. IGFBP-2 and IGFBP-3 concentrations were inversely correlated in the patients with GHRD. When analysed by age, however, IGFBP-2 was related inversely and IGFBP-3 related positively to the age of the patient. The serum IGF-II levels of the male heterozygotes were significantly reduced when compared with sex-matched controls, but considerable overlap with normal values was found. No other biochemical indices were significantly altered in either male or female heterozygotes. Thus, although GHRD is characterized by dramatic reductions in serum levels of GHBP, IGF-I, IGF-II and IGFBP-3, none of these assays provides a reliable biochemical marker for heterozygosity.

Kenny syndrome: evidence for idiopathic hypoparathyroidism in two patients and for abnormal parathyroid hormone in one.

We report three unrelated patients with Kenny syndrome. Clinical symptoms included severe dwarfism, with internal cortical thickening and medullary stenosis of the tubular bones, normal bone age, macrocephaly, absent diploic space, delayed closure of the anterior fontanel, and normal intelligence; two of the patients had hyperopia and papillary edema. The patients also had episodic hypocalcemic tetany and low serum levels of magnesium. In two patients the diagnosis of idiopathic hypoparathyroidism was established on the basis of undetectable serum parathyroid hormone (PTH) levels (N- and C-terminal RIAs); one of these had normal urinary cyclic adenosine monophosphate (cAMP) response to exogenous PTH. Circulating calcitonin was undetectable in either patient. In a third patient, who had abnormal body proportions, serum levels of PTH were increased in an RIA detecting predominantly intact PTH (N-RIA) and undetectable in another RIA recognizing carboxy-terminal fragments (C-RIA). Administration of PTH promptly increased urinary cAMP excretion. In this patient, serum levels of calcitonin were increased, whereas values for 25-OHD and 1,25(OH)2D were normal.

Partial short arm deletions of the X chromosome and spontaneous pubertal development in girls with short stature.

Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.