[Idiopathic short stature. A literature review and update]. / Talla baja idiopática. Revisión y puesta al día.

Idiopathic short stature (ISS) refers to all clinical conditions involving an alteration of growth (height<-2 SD) of unknown cause, with preservation of proportionality among body segments, with the expectation of adult height < -2 SDS, and in which a diagnosis of constitutional delay of growth and development has been previously ruled out. ISS is an exclusion diagnostic which requires clinical, biochemical, hormonal and molecular studies in order to rule out all known causes of growth retardation and short stature. ISS is a frequent diagnosis among children with short stature. Despite its frequency, there is still controversy on the best diagnostic and therapeutic approach when treating patients with ISS. This consensus document contains updated information on the definition, diagnosis and treatment of ISS, and provides new data and recommendations that have not been addressed in previous documents.

[An adolescent with 22q11.2 deletion syndrome and multiple endocrinopathies]. / Adolescente con síndrome de deleción 22q11.2 y endocrinopatía múltiple.

The endocrine abnormalities are common in patients with 22q11.2 deletion, and include hypocalcaemia due to primary hypoparathyroidism, short stature and thyroid dysfunction. We present a patient with delayed diagnosis of del22q11.2 who had multiple endocrine involvement and type 1 diabetes mellitus. A review is also made on the current knowledge of the endocrine manifestations described in patients with 22q11.2 deletion.

[Evaluation of weight, height and BMI in children, adolescents and young adults from the Community of Madrid]. / Valoración del peso, talla e IMC en niños, adolescentes y adultos jóvenes de la Comunidad Autónoma de Madrid.

INTRODUCTION: The data of four growth studies involving populations from Andalusia, Barcelona, Bilbao and Zaragoza have recently been reported as part of the Spanish Cross-sectional Growth Study 2008 (SCGS). With the aim of detecting possible differences between the population of the Madrid region and those of the SCGS, and by so-doing assess the applicability of the conclusions of this reference work to the Madrid region, a cross-sectional study of the latter was undertaken, recording the weight, height and body mass index (BMI). SUBJECTS AND METHODS: We have analyzed 6463 subjects (3055 females and 3408 males) aged 3-24 years. All subjects were healthy, Caucasian, and of Spanish origin. Differences between the results of the Madrid and SCGS studies were sought by multiple linear regression analysis of the log of the height, weight and BMI data adjusted for age and geographical area. The Tukey multiple comparisons test was used to analyse differences in age ranges. All calculations were performed using SAS v. 8.2 software. RESULTS: Means and standard deviations are provided for the weight, height and BMI of women and men; distributions by percentiles are also provided. No differences of clinical importance were seen in the weight, height or BMI between the subjects of the Madrid region and those of the SCGS. However, comparisons with the results of other studies performed more than 20 years ago revealed an increase in the weight and height values in all percentiles. CONCLUSIONS: In summary, the official Spanish SCGS reference data for 2008 are similar to those recorded for the Madrid region. Bearing in mind that recent cross-sectional studies undertaken in Andalusia, Aragon, Catalonia, the Basque Country and the present work show no significant differences in mean weights, heights or BMIs in any age group, nor in the final height attained by adults, the Spanish population would appear to be anthropometrically homogeneous. The conclusions of the SCGS may therefore be applicable to the entire country.

[Chromosome 9P deletion: Gonadal dysgenesis associated with mental retardation and hypoplasia of the corpus callosum: A contiguous gene syndrome?]. / Deleción 9p-. Disgenesia gonadal asociada a retraso mental e hipoplasia del cuerpo calloso. ¿Síndrome de genes contiguos?

BACKGROUND: Many genes are involved in testicular differentiation. The alterations of these genes are responsible for sexual differentiation disorders with 46 XY karyotype. CASE: We report the case of a newborn who had an interscrotal hypospadias, palpable gonads and hypoplastic penis. Karyotype 46 XY. Abdominal ultrasound revealed testes and absence of Müllerian remnants. There was a good response to the short gonadotrophin test. At one year he had signs of psychomotor retardation and hypotonia. The magnetic resonance revealed frontal-temporal atrophy and a decrease in the corpus callosum. Testicular biopsy was compatible with gonadal dysgenesis. A preoperative cystography showed a vaginal remnant. Due to the presence of a sexual differentiation disorder, psychomotor retardation and facial dysmorphism, we requested a high-resolution karyotype: deletion 46, XY, del (9p) (p23-pter). Ish tel (9p-). DISCUSSION: Many genes are involved in testicular differentiation, some of which also affect the development of other tissues. In the short arm of chromosome 9, two genes, DMRT1 and DMRT2, are involved in sexual differentiation. Their alterations have also been described as causing mental retardation. In the evaluation of 46,XY disorders of sex differentiation, the accompanying signs are very important for guiding the genetic study.

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

[Neonatal diabetes mellitus and KCNJ11 gene mutation: report of a family case]. / Diabetes mellitus neonatal y mutación del gen KCNJ11: presentación de un caso familiar.

Neonatal diabetes mellitus (NDM) is characterized by hyperglycemia within the first month of life and insulin dependence for at least two weeks. There are two types of NDM, transient (TNDM) and permanent (PNDM), which are genetically different. We report the case of two brothers who developed hyperglycemia without ketosis on the 18th day and 2 h of life, respectively. Thyroid function tests, abdominal ultrasound and karyotype where normal and there were no pancreatic antibodies. The first one required insulin therapy for the first 92 days of life and the second for 5 months. The mother developed gestational diabetes during both pregnancies and she was later diagnosed diabetes mellitus (without antibodies). They were studied for mutations in KCNJ11 gene (principally related to the permanent form). The three of them showed the E229K mutation (frequently associated with the transient form). A genetic study is essential in NDM to achieve the most accurate prognosis possible.

[11beta-hydroxylase deficiency: improvement of final height with growth hormone and gonadotropin-releasing hormone analog]. / Déficit de 11beta-hidroxilasa: mejoría de talla final con hormona de crecimiento y análogos de LHRH Déficit de 11beta-hidroxilasa: mejoría de talla final con hormona de crecimiento y análogos de LHRH.

Steroid 11beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia. 11beta-hydroxylase intervenes in cortisol synthesis and its deficiency leads to accumulation of adrenal androgens--producing prenatal virilization and, subsequently, hyperandrogenism--as well as 11-deoxycorticosterone, leading to the development of hypertension. We describe a 7-year-old girl who was referred for pubarche and accelerated skeletal maturation due to 11beta-hydroxylase deficiency. Because the patient's predicted height was below her target height, the combination of gonadotropin-releasing hormone analog and growth hormone was added to oral glucocorticoid therapy. With this therapeutic strategy, the patient's predicted height improved significantly and the girl reached a final height in agreement with her target height at the age of 13 years and 6 months.

[Association between WAGR syndrome and diaphragmatic hernia]. / Asociación entre síndrome de WAGR y hernia diafragmática.

Anomalies in WT-1 (Wilms' tumor gene), mapped to 11p13, cause Denys-Drash, Frasier and WAGR syndromes. WAGR syndrome is characterized by Wilms' tumor (W), aniridia (A), genitourinary anomalies (G) and mental retardation (R). In the early human fetus, WT-1 is expressed in the pleural and abdominal mesothelium, and consequently this gene may play a role in diaphragm development. The first report of an association between WAGR syndrome and congenital diaphragmatic hernia has recently been published. We present another infant with aniridia, left cryptorchidism with testicular dysgenesis, right-sided posterolateral diaphragmatic hernia and moderate psychomotor retardation, in whom genetic study showed a deletion of 11p13 and PAX-6, confirming the diagnosis of WAGR syndrome.

[Congenital hyperinsulinism. Review of 22 cases]. / Hiperinsulinismo congénito. Revisión de 22 casos.

INTRODUCTION: Congenital hyperinsulinism (CHI) is the most common cause of recurrent episodes of hypoglycemia in early childhood and consists of a group of distinct genetic disorders causing dysregulation of insulin secretion. OBJECTIVE: To review the presentation, management and outcome of patients with CHI attended at our hospital. MATERIAL AND METHODS: A retrospective review of all patients diagnosed with CHI between 1982 and 2004 was performed. Data were collected on age, gender, clinical presentation, medical and surgical management, and complications. RESULTS: Twenty-two patients were identified. Notable features were early symptom onset in 80 %, pancreatectomy in 72 %, and neurological sequels in 28 % (abnormal neurodevelopment in 22 % and epilepsy in 13 %). CONCLUSIONS: The presentation, management and outcome in our patients were similar to those in other series, indicating the need for early diagnosis and treatment to avoid neurological sequels.

[AIRE gene mutation in polyglandular syndrome type 1]. / Mutación del gen AIRE en el síndrome poliglandular tipo I.

Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal recessive disorder characterized by chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and primary adrenal insufficiency. It has recently been associated with mutations of a single gene found on chromosome 21, designated AutoImmune Regulator (AIRE). We report two patients with APS-1 referred to our hospital for evaluation. The first patient was an 11-year-old girl with hypoparathyroidism, infectious or immunological malabsorption, and autoimmune hepatitis. Hypoparathyroidism associated with other processes with a probable autoimmune origin suggested APS-1. Genetic study was performed revealing deletion of 13 base pairs in exon 8 of the AIRE gene. The second patient was a 17-year-old girl with autoimmune hepatitis, hypoparathyroidism, mucocutaneous candidiasis, nail dystrophy, and obliterating bronchiolitis with a probable autoimmune origin. We suspected APS-1 and genetic study was performed. The only finding was an AIRE gene polymorphism. In conclusion, the presence of a single disease criterion is sufficient to suspect APS-1 and to indicate genetic study. Further studies are required to confirm the involvement of other genes in the development of this disease.

[Idiopathic short stature: definition and treatment]. / Talla baja idiopática: definición y tratamiento.

Short stature is the leading cause of consultation in Pediatric Endocrinology. Decreased growth velocity and abnormally short height are characteristic of several different nosologic entities. Some are well characterized, while others correspond to what is known as idiopathic short stature (ISS). ISS includes children who grow less than 2 SD of the mean height values corresponding to their peers of similar age and the same sex, in whom the known causes of short stature have been ruled out. The diagnosis of ISS does not include children who only present a constitutional delay in growth and development. Several clinical trials have demonstrated the efficacy of growth hormone (rhGH) treatment in achieving catch-up growth in these children. Therefore, ISS should be kept in mind in the diagnosis of patients with short stature and abnormal growth patterns, who may benefit from rhGH treatment.

[Macroorchidism: a case report]. / Macroorquidismo: a propósito de un caso.

Macroorchidism is a rare condition in children and is usually associated with fragile X syndrome. Other possible etiologies of macroorchidism are long-standing primary hypothyroidism, adrenal remnants in congenital adrenal hyperplasia, follicle stimulating hormone (FSH)-secreting pituitary macroadenomas, local tumors, lymphomas, and aromatase deficiency. Bilateral macroorchidism can be a normal variant in adult men. We report the case of an 11.5-year-old boy who was referred to our hospital for evaluation of marked bilateral testicular enlargement in the previous few months. Physical examination revealed a testicular volume larger than 30 ml. Complementary investigations allowed us to rule out all hitherto reported etiologies of bilateral macroorchidism and therefore a diagnosis of idiopathic macroorchidism was established. The increased number of Sertoli cells found on biopsy, without elevated plasma FSH levels, prompted us to speculate about a hypothetical FSH receptor hyperfunction as a possible cause of the exaggerated testicular enlargement in this patient.

[Williams-Beuren syndrome: presentation of 82 cases]. / Síndrome de Williams-Beuren: presentación de 82 casos.

OBJECTIVE: We performed a retrospective review of a series of 82 cases of Williams-Beuren syndrome (WBS) and associated diseases. MATERIAL AND METHODS: A series of 82 patients (47 males and 35 females) who consulted at the hospital because of mental retardation and/or congenital cardiopathy were included. The patients were studied mainly from a neurological and cardiological point of view, and secondarily because of endocrinological and nephrological problems. Since description of the chromosomal abnormalities provoking the syndrome, we perform karyotyping in all patients with suspected WBS. RESULTS: Alterations mainly consisted of distinctive facial appearance (100 %), mental retardation with friendly behavior (90 %), congenital cardiopathy (85.4 %), mostly consisting of supravalvular aortic stenosis (72 %), with (12 %) or without (60 %) pulmonary stenosis, and behavior typical of attention deficit-hyperactivity disorder, which usually manifested at the age of 4 to 5 years in both boys and girls. Approximately 90 % started to walk and speak later than average. Birthweight was below 3000 g in 65 % of the patients in whom this datum was included in the medical record. Eleven of the 13 patients (84.5 %) studied showed the typical deletion of WBS. CONCLUSION: Study of patients with WBS should be multidisciplinary. Most patients require help during schooling and subsequent vocational guidance.