Phenotypic homogeneity and genotypic variability in a large series of congenital isolated ACTH-deficiency patients with TPIT gene mutations.

CONTEXT: Congenital isolated ACTH deficiency (IAD) is a rare disease characterized by low plasma ACTH and cortisol levels and preservation of all other pituitary hormones. This condition was poorly defined before we identified TPIT, a T-box transcription factor with a specific role in differentiation of the corticotroph lineage in mice and humans, as its principal molecular cause. OBJECTIVE: We have enlarged our series of IAD patients to better characterize the phenotype and the genotype of this rare disease. DESIGN: Each exon of the TPIT gene was amplified and sequenced in IAD patients without any identified cause. A functional analysis of each new TPIT mutation was performed. RESULTS: We described the largest series of 91 IAD patients and identified three distinct groups: neonatal onset complete or partial IAD or late onset IAD. We did not identify any TPIT mutation in patients with partial or late-onset IAD. However, we found a TPIT mutation in 65% of patients with neonatal-onset complete IAD. These patients are homozygous or compound heterozygous for TPIT mutations, and their parents are healthy heterozygous carriers. We identified nine new mutations: four missense, one one-nucleotide deletion, three splice-site mutations, and one large deletion. TPIT mutations lead to loss of function by different mechanisms, such as non-sense-mediated mRNA decay, abnormal mRNA splicing, loss of TPIT DNA binding or protein-protein interaction defects. CONCLUSION: TPIT mutations are responsible for two thirds of neonatal-onset complete IAD but can not be detected in partial or late-onset IAD.

Variations of the paranasal sinuses in Melanesians as observed by CT.

Studies have reported the incidence of anatomical variants of the paranasal sinuses for specific populations with a view to helping surgeons avoid possible complications during functional endoscopic sinus surgery. Some have found significant variation when comparing different populations. The current study has used computed tomography (CT) scans to observe variations in the paranasal sinuses in a non-random sample of museum skulls of Melanesians, a racial group that has not previously been studied in this respect. The incidence of variants found were: agger nasi cells 59.5%, concha bullosa 41.5%/o, Haller's air cells 31.7%, internal carotid artery bulge in the sphenoid sinus 23.8%/, supraorbital cells 16. 7%, paradoxical curvature of the mid-dle turbinate 7.5% and pneumatization of crista galli 7.1%.Because of contradictory findings in the literature as to the incidence of such variations between racial groups the authors are able to make only limited meaningful comparisons between their subjects and other such groups.

Medial meniscus posterior root attachment injury and degeneration: MRI findings.

The posterior root attachment of the medial meniscus is readily identifiable on MRI. Unless specifically reviewed, injuries involving this structure may be overlooked. Significant meniscal root pathology may cause functional incompetence of the meniscus, with consequent early onset cartilage degeneration and osteoarthritis. This review article emphasizes the importance of positive identification of an intact meniscal root and illustrates the known association of meniscal root injury or tear with medial extrusion of the medial meniscus by greater than 3 mm beyond the joint margin.

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. This report presents the clinical and genotypic findings of 30 French families, for whom a diagnosis of Pendred's syndrome had been made. Twenty-seven families had at least one mutated allele. Twenty-eight different mutations were identified, 11 of which had never been previously reported. The main clinical characteristics were: early hearing loss, fluctuation in terms of during deafness evolution, and the presence of an enlarged vestibular aqueduct.

Hypogonadotrophic hypogonadism associated with prelingual deafness due to a connexin 26 gene mutation.

In Mediterranean countries, almost half the incidence of non-syndromic congenital hearing loss is caused by mutations in the gap junction (GJ) connexin 26 gene (GJB2/DFNB1 locus). In this form of deafness the cochlear defect is usually isolated. We describe here the first case of hypogonadotrophic hypogonadism in association with this particular cochlear defect. The male patient had moderate deafness inherited from his deaf parents. All family members had a homozygous 35delG mutation in the connexin 26 gene. This mutation accounts for 70% of all connexin 26 gene mutations. The patient was referred to a paediatric endocrinology unit at 11 years of age for moderate growth retardation. Growth rate was normal until 11 years. The patient then presented delayed puberty (testicular volume 4 ml, penis length 4 cm) and did not undergo the usual pubertal growth spurt. LH and FSH secretory responses to GnRH at the age of 14.5 years (bone age 13.5 years), were: LH baseline level 1.1 IU/l, peak 34 IU/l; FSH baseline level 1.8 IU/l, peak 5.7 IU/l. Testosterone concentration was <0.11 ng/ml. From 11 to 14 years old, testosterone concentration ranged from 0.11 to 0.2 ng/ml. Anti-Mullerian hormone (AMH) level was 38.6 ng/ml (normal for Tanner stage I), cortisol 109 ng/ml, and ACTH 37 pg/ml., Karyotype was 46 XY. On MRI analysis, the anterior pituitary and olfactory bulbs were normal. These data were consistent with partial hypogonadotrophic hypogonadism of hypothalamic origin, and the patient was treated with testosterone. This report supports the possible involvement of connexins in puberty initiation. Connexins may play a part in the co-ordination and synchronisation of GnRH release.

Follow up of precocious pseudopuberty associated with isolated ovarian follicular cysts.

The clinical outcomes of seven girls presenting with pseudosexual precocity caused by isolated autonomous ovarian follicular cysts are presented. Six of the seven girls, aged 11 months to 6.9 years, had a unilateral ovarian cyst detected by ultrasound at the first acute episode. Plasma oestradiol was raised in only five of the cases, but all had a low response to luteinising hormone releasing hormone stimulation. Follow up lasted for up to eight years with recurrent episodes of variable frequency and severity in all seven patients. Evidence of McCune-Albright syndrome appeared later in only three patients. It could not be predicted from the initial symptoms or the clinical course. Mutations of the G(s)alpha protein leading to activation were investigated in the lymphocytes and ovarian and bone tissues of four patients. Only one patient showed a mutation in bone tissue. Close follow up with repeated searches for skeletal lesions remains necessary since the distribution of somatic mutations cannot be assessed by molecular studies. Most patients with recurrent ovarian cysts require a conservative approach.

[Acute urine retention: a rare mode of revelation of cervico-dorsal syringomyelia caused by cyproheptadine]. / Rétention aiguë d'urines: un mode de révélation rare d'une syringomyélie cervicodorsale à l'occasion de la prise de cyproheptadine.

BACKGROUND: Syringomyelia is rare in children aged less than 10 years, and bladder dysfunction is an unlikely first manifestation. This report describes a case of repeated episodes of acute urinary retention in a young girl revealing syringomyelia and Arnold-Chiari malformation. CASE REPORT: A 2.5 year-old girl was admitted because she was suffering from acute urinary retention. Her poor appetite had been treated with cyproheptadine, a histamine type I blocking drug. Clinical investigation revealed no local cause for this bladder dysfunction except moderate spasticity of the legs. Cystography showed no vesicoureteral reflux. Because the episodes of urinary retention recurred each day, magnetic resonance imaging (MRI) was performed; this showed the typical features of syringomyelia extending from C5 to T11 plus Arnold-Chiari malformation. The cyproheptadine was discontinued and the urinary retention disappeared. CONCLUSION: Cyproheptadine may have revealed latent neurogenic bladder in this case, although urodynamic studies, performed 3 months later, detected no bladder dysfunction.

Diagnosis of a posterior fossa tumour by magnetic resonance imaging.

The application of magnetic resonance imaging as a diagnostic tool for diseases of the central nervous system is described in the case of a 17-year-old girl who presented with neurological symptoms in January 1986. A comparison is made with the results of computed tomography in the diagnosis of the disease, which proved to be a grade-III glioma that appeared as a lesion of the posterior fossa. The patient recovered uneventfully after radiotherapy. It is suggested that MRI should be considered seriously as a first line of investigation in any suspected lesion of the posterior fossa.

Computerized axial tomography in the pretreatment assessment of small-cell carcinoma of the bronchus.

Computerized axial tomographic scans (CAT scans) of thorax and abdomen were used as part of the initial staging procedure of 50 consecutive patients with small-cell bronchogenic carcinoma (SCBC). The aims were to define the extent of the primary tumor and metastatic spread, and to compare the information obtained from CAT scans with conventional staging procedures. With CAT scanning, spread of the primary tumor was found to be far more extensive than originally believed when defined by conventional assessment. Of 35 patients conventionally staged as localized T1 or T2 tumors, 27 (77%) had their stage increased to extensive T3 disease. similarly, subcarinal lymph nodes were found in one patient when conventional methods were used (2%), but 16 patients (32%) were found when CAT scan was used. Unsuspected adrenal metastases were found in eight patients (16%) and retrocrural nodes in four patients (8%). Thirty-seven patients (74%) were found to have Stage III tumors when conventional staging was used; 47 patients (94%) were found to be Stage III following CAT scanning, demonstrating that, within the thorax, localized tumors are very uncommon. CAT scanning demonstrates the degree of intrathoracic spread very clearly, and has a valuable role in the initial investigation of patients with SCBC if the planned treatment includes radiotherapy.

The clinical application of computed tomography in the assessment of laryngo-pharyngeal carcinoma. (Preliminary report).

Computed axial tomography of the larynx offers a unique view of laryngeal structures which cannot be obtained by any other technique. Its applications are discussed and cases presented to demonstrate its usefulness.

Correlation between computed tomographic values and liver iron content in thalassaemia major with iron overload.

Computer tomographic (CT) scans of the liver were obtained in six thalassaemic patients with iron overload confirmed by liver biopsy. Mean CT values for the liver in individual patients were linearly related to the iron content estimated by liver biopsy (correlation coefficient = 0.995).