Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2.

Kallmann syndrome combines anosmia, related to defective olfactory bulb morphogenesis, and hypogonadism due to gonadotropin-releasing hormone deficiency. Loss-of-function mutations in KAL1 and FGFR1 underlie the X chromosome-linked form and an autosomal dominant form of the disease, respectively. Mutations in these genes, however, only account for approximately 20% of all Kallmann syndrome cases.

[Scholarly and occupational outcomes of the first patients screened in France for congenital hypothyroidism].

A population of 74 young adults born between 1 Jan. 1979 and 30 June 1985 who were screened at birth for congenital hypothyroidism received a questionnaire on their scholastic and occupational achievements in June 2003. The response rate was 74% (49 completed questionnaires and 8 postal returns).

Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of mutations in France and phenotypic heterogeneity.

Sensorineural hearing defect and goiter are common features of Pendred's syndrome. The clinical diagnosis of Pendred's syndrome remains difficult because of the lack of sensitivity and specificity of the thyroid signs. The identification of PDS as the causative gene allowed molecular screening and enabled a re-evaluation of the syndrome to identify potential diagnostic characteristics.

Earlier onset of treatment or increment in LT4 dose in screened congenital hypothyroidism: which as the more important factor for IQ at 7 years?

Objective: To determine between timing and LT4 dose which was the more important factor for IQ at 7 years in screened congenital hypothyroidism (CH).

Methods: 131 children with CH born from 1979 to 1994 and 30 controls were studied. Mean age at recall: 22.

Adult height in congenital hypothyroidism: prognostic factors and the importance of compliance with treatment.

Objective: To study the growth, puberty and compliance of 66 hypothyroid children and to determine prognostic factors for adult height.

Patients: 66 children were included (12 boys, 54 girls). Aetiologies were 43 ectopic glands, 14 thyroid agenesis, 9 dyshormonogenesis.

Townes-Brocks syndrome: detection of a SALL1 mutation hot spot and evidence for a position effect in one patient.

Townes-Brocks syndrome (TBS) is an autosomal dominant developmental disorder characterized by anal and thumb malformations and by ear anomalies that can affect the three compartments and usually lead to hearing loss. The gene underlying TBS, SALL1, is a human homolog of the Drosophila spalt gene which encodes a transcription factor. A search for SALL1 mutations undertaken in 11 unrelated affected individuals (five familial and six sporadic cases) led to the detection of mutations in nine of them.

[Results of national evaluation tests (primary schools) of CE2 and 6th classes of 73 students with congenital hypothyroidism screened at birth].

Unlabelled: Assessment of school performance provides an excellent index of adequacy of therapy of congenital hypothyroidism.

Patients And Methods: Scholarly achievement of 73 children with congenital hypothyroidism screened and followed-up in our clinic was evaluated by comparison to national tests calculated from a wide random sample. The 73 children were divided into three groups: 31 patients belonging to the CE2 class (third primary school class) (group 1); 13 patients belonging to the 6th class (first secondary school class) having already passed CE2 tests (group 2); and 16 patients also belonging to the 6th class but not having passed CE2 tests (group 3).

Two cases of Townes-Brocks syndrome with previously undescribed anomalies.

Townes-Brocks syndrome is characterized by the association of anorectal, radial ray and outer ear malformations and deafness. We describe two patients affected with several typical clinical signs of Townes-Brocks syndrome in addition to growth and puberty delays and vertebral anomalies not previously reported.

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation.

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.

[Psychosocial and sexual outcome in women with Turner syndrome].

Results of an inquiry in adults patients (18-53 years of age) coming from three centers (1 in Rouen & 2 in Paris), 213 questionnaires were sent. 105 answers were received. Scholar achievement: only secondary cycle in 6%, Secondary cycle + professional course in 22% and tertiary cycle in 44%.

Modifications of growth hormone secretion during female puberty.

Growth hormone levels rise steadily through normal puberty, in parallel with the pubertal stages but decline rapidly at the end of puberty (stage V). The general evolution of the secretory profile of GH is parallel to the growth velocity curve. The frequency of GH pulses remains unchanged; however, their amplitude, mean integrated concentrations, area under the curve, and urinary growth hormone are elevated at midpuberty.

A thyroxine dosage of 8 micrograms/kg per day is appropriate for the initial treatment of the majority of infants with congenital hypothyroidism.

Unlabelled: The adequate L-thyroxine dosage for the initial treatment of infants with congenital hypothyroidism is a subject of controversy. Some recommend higher dosages (> 10 micrograms/kg/day) to ensure adequate levels, while others advocate lower dosages to permit normalisation of thyroid status. The aim of this study was to evaluate the results of a treatment strategy using an initial dosage of 7.

Four families with loss of function mutations of the thyrotropin receptor.

We observed four families with loss of function mutations of the TSH receptor gene. One patient had a homozygous Pro162 Ala substitution. The three other were compound heterozygotes: 1) Gln324-->Stop and Asp410 Asn2), Cys41 Ser and Phe525 Leu, 3) Cys390 Trp and Trp546-->Stop.

[Alpha fetoprotein in congenital hypothyroidism before and during treatment].

Background: Screening for congenital hypothyroidism (CH) is an opportunity to investigate maturation by measuring alphafetoprotein (AFP).

Patients And Methods: Blood AFP was measured in 73 full-term infants (controls), 22 infants with permanent CH and 19 with a transient form (FT) of hypothyroidism. It was also measured in mothers of the two groups with hypothyroidism.

Clinical and anatomical spectrum in XX sex reversed patients. Relationship to the presence of Y specific DNA-sequences.

Objective: Testicular differentiation can occur in the absence of the Y chromosome giving XX sex-reversed males. Although Y chromosomal sequences can be detected in the majority of male subjects with a 46,XX karyotype, several studies have shown that approximately 10% of patients lack Y material including the SRY gene. The aim of this study was to see if the classification of XX sex-reversed individuals into three groups, Y-DNA-positive phenotypically normal XX males, Y-DNA-negative XX males with genital ambiguities and Y-DNA-negative true hermaphrodites can be applied to our cases.

[Management of female precocious puberty].

Occurrence of any pubertal sign before eight years of age defines premature sexual development but does not always mean precocious puberty (PP); one should distinguish borderline physiological situations which need only a follow-up and frankly pathological situations which need very precise investigations and suitable treatment. The first situations are premature thelarche, pubarche and menarche in which the height and bone maturation, pelvic ultrasonography (US) are normal for age, avoiding hormonal investigations. Conversely in the second situation, the bone age is more advanced than the height age and the pelvic US displays ovarian activity and uterine development.

Molecular prenatal diagnosis of partial androgen insensitivity syndrome based on the Hind III polymorphism of the androgen receptor gene.

Objective: Partial androgen insensitivity syndromes are the cause of genital ambiguity that is at times quite severe; there is, therefore, a high demand for prenatal diagnosis in families already afflicted with this syndrome. When the mutation has not been identified, the diagnosis can be made by the study of the polymorphisms of the androgen receptor gene. To perform molecular prenatal diagnosis in a family with partial androgen insensitivity syndrome, we studied the Hind III polymorphism of the androgen receptor gene on the trophoblastic DNA.

[Study of sex determination gene (SRY) in 46,XY gonadal dysgenesis].

During mammalian embryogenesis, the presence of the SRY gene determines the bipotential gonad to develop as a testis. 46,XY sex reversal has been described in man. It is associated with an essentially female phenotype and a streak gonad.

Growth of short normal children in puberty treated for 3 years with growth hormone alone or in association with gonadotropin-releasing hormone agonist.

GH, 0.1 IU/kg/day 6 days/week, was given to 30 early pubertal short patients for 3 years. There were 16 males, aged 14.

Hormonal and molecular genetic findings in 46,XX subjects with sexual ambiguity and testicular differentiation.

Ten patients were studied who had sexual ambiguity having in common a 46.XX karyotype and testicular tissue. They were aged from one month to 23 years; some of them were followed through puberty.

Prenatal prediction of androgen insensitivity syndrome using exon 1 polymorphism of the androgen receptor gene.

Exon 1 polymorphism of the androgen receptor (AR) gene is characterized by a (CAG)n(CAA) repeat at position 172 following the translation start codon. The aim of this study was to determine whether AR gene exon 1 polymorphism could be used to perform prenatal diagnosis in high risk families with complete or partial androgen insensitivity syndrome. After enzymatic amplification of a 1 kilobase exon 1 fragment, each DNA was simultaneously digested by MspI and PstI restriction enzymes.

Screening for Y-derived sex determining gene SRY in 40 patients with Turner syndrome.

In Turner patients, the presence of a Y chromosome or derivative Y is correlated with the risk of gonadoblastoma induction. "Marker" chromosomes originating from Y, may not show characteristic fluorescence and then be very difficult to identify by conventional cytogenetic techniques, although they still predispose the patients to gonadal tumors. Using polymerase chain reaction of the gene from the sex-determining region of the Y chromosome, we screened 40 Turner patients (thirty seven 45X and three 45X,46XX) for the presence of Y chromosomal DNA.