Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure.

Costello syndrome is a rare multisystem disorder caused by mutations in the proto-oncogene HRAS. Failure to thrive is one of its cardinal clinical features. This study documents that individuals with Costello syndrome have increased resting energy expenditure. We speculate this could be one of the potential mechanisms causing failure to thrive.

Hashimoto's thyroiditis: an accidental discovery of a lingual thyroid in a 7-year-old child.

An ectopic thyroid located at the base of the tongue is a rare entity, resulting from early developmental defects of thyroid gland embryogenesis during its descent from the foramen caecum to its normal eutopic pretracheal site. This condition is the main cause of congenital primary hypothyroidism, even though signs and symptoms of thyroid dysfunction may also appear later in childhood. Lingual thyroid may sometimes present with symptoms of respiratory obstruction or feeding difficulties. We illustrate the case of a 7-year-old girl with subclinical hypothyroidism due to Hashimoto's thyroiditis arising in a lingual thyroid. She had never suffered from upper airway obstructive symptoms, but did refer a 3-month history of cough. Rapid normalisation of thyroid-stimulating hormone levels and termination of the cough were attained when the L-thyroxine treatment started. After 6 months a significant reduction of lingual thyroid size was also noted. The diagnostic procedures and therapeutic options in childhood are discussed.

Ovarian volume and gluco-insulinaemic markers in the diagnosis of PCOS during adolescence.

OBJECTIVE: To evaluate the role of mean ovarian volume (MOV) in the diagnosis of polycystic ovary syndrome (PCOS) during adolescence, and its relationship with metabolic and endocrine parameters. DESIGN: Observational study. PATIENTS: A total of 134 young girls, including 86 adolescents with PCOS and 48 controls, were studied. MEASUREMENTS: During the early follicular phase, a pelvic ultrasound examination was performed to measure the ovarian volume of both ovaries and to calculate the MOV. All subjects underwent hormonal assessment and an ultrasound examination. PCOS subjects were submitted to an oral glucose tolerance test. The homeostasis model assessment for insulin resistance (HOMA-IR) and several insulin resistance indexes were also determined. RESULTS: Androgens, free androgen index (FAI), LH and insulin resistance indexes were higher in the PCOS group. MOV was significantly different between the two groups: control group 4·6 ± 1·9 cm(3) , adolescent PCOS group 9·6 ± 4·4 cm(3) . The MOV threshold of 5·596 cm(3) offered the best compromise between sensitivity and specificity based on the characteristics of the operating receiver curve analysis. Therefore, an ovarian volume higher than 5·6 increased the risk of PCOS by about 15 times (OR 16·25 IC 95% 6·3-41·3). In adolescent PCOS girls, the ovarian volume was significantly associated with circulating testosterone and insulin, and indices of insulin resistance. CONCLUSIONS: During early adolescence MOV evaluation may offer an effective means to screen and follow up young girls with irregular cycles in order to prevent the long-term metabolic disturbances of the polycystic ovary syndrome.

Chromosome 9p deletion syndrome and sex reversal: novel findings and redefinition of the critically deleted regions.

Deletions of the short arm of chromosome 9 are associated with two distinct clinical entities. Small telomeric 9p24.3 deletions cause genital anomalies in male subjects, ranging from disorder of gonadal sex to genital differentiation anomalies, while large terminal or interstitial deletions result in 9p-malformation syndrome phenotype. The critical region for non-syndromic 46,XY sex reversal was assigned to a 1 Mb interval of chromosome 9p, extending from the telomere to the DMRT genes cluster. The 9p-syndrome was assigned to bands 9p22.3p24.1, but a phenotypic map has not been established for this condition, probably because of the lack of detailed molecular and/or phenotypic characterization, as well as frequent involvement of additional chromosome rearrangements. Here, we describe a unique patient with a small isolated 9p terminal deletion, characterized by array-CGH and FISH, who shows a complex phenotype with multiple physical anomalies, resembling the 9p-syndrome, disorder of sex development with gonadoblastoma, congenital heart defect and epilepsy. The observed deletion includes the 46,XY sex-reversal critical region, excluding the region so far associated with the 9p-syndrome. Genotype-phenotype correlations are tentatively established comparing our patient to seven other previously reported males with isolated terminal 9p deletions, finely defined at a molecular level. Our observations expand the 9p deletion clinical spectrum, and add significantly to the definition of a 9p-syndrome critical region.

Incidental finding of idiopathic unilateral adrenal calcification in an 18-month-old child: case report and review of the literature.

The presence of calcified lesions in the adrenal gland requires a careful endocrine, microbiological and radiological evaluation combined with detailed clinical history to confirm its non-evolving nature and avoid unnecessary surgery. We report an 18-month-old male child hospitalized with an incidentally discovered calcification in his right adrenal gland. All biochemical data as well as liver, renal and adrenal function tests were normal. Abdominal computed tomography scan showed that the right adrenal gland was completely occupied by a large calcification, which was put in relationship with an undetected adrenal distress during the neonatal period, as macrosomy and clavicle fracture of the newborn could let us suggest. Our report describes the diagnostic approach to disclose the nature of a suprarenal mass, which is particularly problematic when this is found incidentally. In addition, an extensive review of the medical literature dealing with non-traumatic adrenal calcifications and haemorrhages in children has been carried out.

Functional analysis of two rare CYP21A2 mutations detected in Italian patients with a mildest form of congenital adrenal hyperplasia.

BACKGROUND: More than 90% of all cases of congenital adrenal hyperplasia (CAH) result from steroid 21-hydroxylase gene (CYP21A2) mutations. Most of these mutations result from intergenic recombinations between CYP21A2 and closely linked CYP21A1P pseudogene. Rare mutations not generated by gene conversion account for 5-10% of 21-hydroxylase deficiency alleles. OBJECTIVE: Functional analysis of two novel CYP21A2 missense mutations (p.R224W and p.D407N) was performed. DESIGN: Our study was composed of two Italian patients suffering from a very mild form of nonclassic CAH (NC-CAH). To assay the enzymatic activity of mutants, the in vitro analysis was performed in transiently transfected COS-1 cells. RESULTS: The residual activities obtained for p.R224W and p.D407N mutants allow their classification as NC-CAH mutations. These results correlate with the rate of severity of the patients' disease. CONCLUSIONS: In this paper, we report two novel CYP21A2 mutations in two Italian individuals affected by 21-hydroxylase deficiency. Based on the functional in vitro analysis we can classify these mutations as NC-CAH variants.

A novel MEN1 frameshift germline mutation in two Italian monozygotic twins.

BACKGROUND: This report describes clinical, biochemical and molecular findings regarding two Italian monozygotic twins carrying a novel multiple endocrine neoplasia type 1 (MEN1) mutation inherited from their mother. METHODS: Clinical, biochemical and genetic evaluations of the above-mentioned family members were performed. RESULTS: All three members were heterozygous for a deletion involving the first nucleotide at codon 98 in exon 2 of the MEN1 gene, which results in early termination of the protein. The clinical phenotypes were as follows: one out of the two twins suffered from insulinoma and hyperparathyroidism, while the second one was asymptomatic. Furthermore, the mother suffered from hyperparathyroidism, as well as from hypergastrinemia for several years before the daughter was diagnosed of MEN-1. CONCLUSIONS: We describe a family with a new heterozygous mutation (g.292delC) in the MEN1 gene not described previously. The mutation leads to a truncated protein without activity, explaining the clinical picture of this family.