Absence of inactivating mutations and deletions in the DMRT1 and FGF9 genes in a large cohort of 46,XY patients with gonadal dysgenesis

Despite advances in our understanding of the mechanisms involved in sex determination and differentiation, the specific roles of many genes in these processes are not completely understood in humans. Both DMRT1 and FGF9 are among this group of genes. Dmrt1 controls germ cell differentiation, proliferation, migration and pluripotency and Sertoli cell proliferation and differentiation. Fgf9 has been considered a critical factor in early testicular development and germ cell survival in mice. We screened for the presence of DMRT1 and FGF9 mutations in 33 patients with 46,XY gonadal dysgenesis. No deletions in either DMRT1 or FGF9 were identified using the MLPA technique. Eight allelic variants of DMRT1 were identified, and in silico analysis suggested that the novel c.968-15insTTCTCTCT variant and the c.774G>C (rs146975077) variant could have potentially deleterious effects on the DMRT1 protein. Nine previously described FGF9 allelic variants and six different alleles of the 3' UTR microsatellite were identified. However, none of these DMRT1 or FGF9 variants was associated with increased 46,XY gonadal dysgenesis. In conclusion, our study suggests that neither DMRT1 nor FGF9 abnormalities are frequently involved in dysgenetic male gonad development in patients with non-syndromic 46,XY disorder of sex development. (C) 2012 Published by Elsevier Masson SAS.

Advice on the Management of Ambiguous Genitalia to a Young Endocrinologist from Experienced Clinicians

The birth of a child with ambiguous genitalia is a challenging and distressing event for the family and physician and one with life-long consequences. Most disorders of sexual differentiation (DSD) associated with ambiguous genitalia are the result either of inappropriate virilization of girls or incomplete virilization of boys. It is important to establish a diagnosis as soon as possible, for psychological, social, and medical reasons, particularly for recognizing accompanying life-threatening disorders such as the salt-losing form of congenital adrenal hyperplasia. In most instances, there is sufficient follow-up data so that making the diagnosis also establishes the appropriate gender assignment (infants with congenital adrenal hyperplasia, those with androgen resistance syndromes), but some causes of DSD such as steroid 5 alpha-reductase 2 deficiency and 17 beta-hydroxysteroid dehydrogenase deficiency are associated with frequent change in social sex later in life. In these instances, guidelines for sex assignment are less well established.

DSD Due to 5 alpha-Reductase 2 Deficiency - from Diagnosis to Long Term Outcome

Most of the patients with 5 alpha-RD 2 deficiency are reared in the female social sex due to their severely undervirilized external genitalia but similar to 60% who have not been submitted to orchiectomy in childhood undergo male social sex change at puberty. In our cohort of 30 cases from 18 families, all subjects were registered in the female social sex except for two children-one who had an affected uncle and the other who was diagnosed before being registered. The majority of the patients were satisfied with the long-term results of their treatment and surprisingly, penile length was not associated with satisfactory or unsatisfactory sexual activity. Steroid 5 alpha-RD2 deficiency should be included in the differential diagnosis of all newborns with 46,XY DSD with normal testosterone production before gender assignment or any surgical intervention because these patients should be considered males at birth.

Osteosarcoma arising from osteochondroma of the tibia: case report and cytogenetic findings

Osteochondroma is a cartilage capped benign tumor developing mainly at the juxta-epiphyseal region of long bones. The rate of malignant transformation, mainly into chondrosarcoma, is estimated to be less than 1-3%. Transformation into osteosarcoma is very rare and has been reported only thirteen times. There is little information on treatment and outcome. We report the case of a secondary osteosarcoma arising in the left tibia of a 23-year-old male, 10 years after the initial diagnosis of osteochondroma and after two partial resections. Malignant transformation occurred at the stalk and not at the cartilage cap, as would normally be expected. Chromosome banding analysis revealed the karyotype: 46,XY, t(3;13)(q21;q34) [2]/46,XY [18]. Records from additional cases will help determine the parameters that define these rare secondary bone lesions.

Temporomandibular disorders in headache patients

Objective: To identify the frequency of signs and symptoms of temporomandibular disorder (TMD) and its severity in individuals with headache. Study Design: 60 adults divided into three groups of 20 individuals: chronic daily headache (CDH), episodic headache (EH) and a control group without headache (WH). Headache diagnosis was performed according to the criteria of International Headache Society and the signs and symptoms of TMD were achieved by using a clinical exam and an anamnestic questionnaire. The severity of TMD was defined by the temporomandibular index (TMI). Results: The TMD signs and symptoms were always more frequent in individuals with headache, especially report of pain in TMJ area (CDH, n=16; EH, n=12; WH, n=6), pain to palpation on masseter (CDH, n=19; EH, n=16; WH, n=11) which are significantly more frequent in episodic and chronic daily headache. The mean values of temporomandibular and articular index (CDH patients) and muscular index (CDH and EH patients) were statistically higher than in patients of the control group, notably the articular (CDH=0.38; EH=0.25; WH=0.19) and muscular (CDH=0.46; EH=0.51; WH=0.26) indices. Conclusions: These findings allow us to speculate that masticatory and TMJ pain are more common in headache subjects. Besides, it seems that the TMD is more severe in headache patients.

Social Skills and Psychological Disorders: Converging and Criterion-Related Validity for YSR and IHSA-Del-Prette in Adolescents at Risk

This study evaluated indexes of converging and criterion-related validity for the Social Skills Inventory for Adolescents (IHSA-Del-Prette) and the Youth Self-Report (YSR) in two samples: one referring to clinical service (CLIN), with 28 adolescents (64.3% boys), 11 through 17 years old (M = 13.75; SD = 1.74), and the other referring to a psycho-educational program (PME = 46.2%), mainly composed of boys (91.7%) aged 13 through 17 (M = 15.33; SD = 1.47). Both samples completed the two inventories. Results showed a high incidence of psychological disorders in both samples (between 4% and 79% in the borderline or clinical range on YSR scales) and accentuated deficits in the general and subscale scores of IHSA-Del-Prette, especially on the frequency scale (25% to 58%). The correlations between the instruments in the two groups supported criterion-related and converging validity. Some issues concerning the differences between the samples and about the construct of social competence, underlying these inventories, are discussed. Key words authors: