Germ-line deletion involving the INK4 locus in familial proneness to melanoma and nervous system tumors.

Joint predisposition to malignant melanoma and nervous system tumors (NSTs) is a puzzle. Several melanoma susceptibility genes have been identified, including p16, a clustered tumor suppressor. However, the molecular bases of inherited proclivity to NSTs in the absence of a recognizable genetic syndrome are unknown. We analyzed two families with joint proneness to melanoma and NSTs in view of genetic linkage and identification of the causal molecular lesions. Highly informative linkage markers were used for segregation analyses of the predisposition alleles in the two pedigrees. Characterization of the molecular lesions required hemizygosity mapping based on microsatellite markers physically mapped to contigs of the 9p21 region and a Southern blot approach using several PCR-generated probes. Both families were found to be allelic and linked to p16 markers. In the family segregating the melanoma/NST syndrome, a large germ-line deletion ablated the whole p16, p19, and p15 gene cluster (or INK4 locus), whereas a more circumscribed molecular lesion disrupting p16 and p19 but leaving p15 unaltered segregated with the melanoma-astrocytoma syndrome (MIM 155755). Our results suggest that multiple cancer susceptibility in these two families ensues from contiguous tumor suppressor gene deletion. Indeed, known phenotypes associated with germ-line p16 mutations and an apparent correlation between the deletion span and tumor spectrum in the two families suggest a new model of cancer pathogenesis based on the inactivation of contiguous tumor suppressor genes, an alternative to the established pleiotropic effects of single-gene disruption.

[Familial forms of interauricular communication of the ostium secundum type]. / Les formes familiales de communication interauriculaire de type ostium secundum.

The occurrence of several cases of ASD in the same family is rare. Familial forms of ASD are characterised by the high incidence of associated cardiac lesions in affected patients or in the family, by the frequency of atrioventricular block with prolongation of the PR interval and by the presence of a large defect in the interatrial septum. The condition is thought to be transmitted in an autosomal dominant manner. The authors report the case of a family in which 7 cases of ASD were found, 6 of which were repaired surgically. There were no associated cardiac or extracardiac malformations; AV conduction was normal in 4 of the 6 operated cases--the defects were all large. The study of the genealogical tree with examination of most members of the family suggests autosomal dominant transmission of the condition.

[Congenital desproportion of various types of muscle fiber, with relative small size of type I fibers. Morphological documents on muscle biopsies in 3 members of the same family]. / Disproportion congénitale des différents types de fibre musculaire, avec petitesse relative des fibres de type I. Documents morphologiques concernant les biopsies musculaires prélevées chez trois membres d'une même famille

In two sisters with a neo-natal hypotonia, muscle biopsies demonstrated as main pathological feature a disproportion in size between the two types of muscle fibers defined according to their myofibrillar ATPase activity. Type I fiber mean diameter was at the lower limit of the normal values, and type II fibers were larger than normal. Their father's biopsy also showed an abnormal smallness of the type I fibers, with a bimodal distribution. By electron microscopy, the small type I fibers did not reveal any significant abnormality in children's biopsies. In father's biopsy, there was an abnormal degree of filamentary interchange between contiguous myofibrils and a few stacks of rods in the type I fibers. These three cases demonstrate the familiar character of the disorder. The relationship of this new entity with the other congenital myopathies is controversial, as a similar congenital fiber type disproportion, has been found in association with different ultrastructural changes. Several data favour an insufficient development of the type I fibers rather than an atrophying process. The mechanism of this "hypotrophy" remains unknown.

[Acute basal ganglia necrosis with favorable course during Mycoplasma encepahlitis]. / Nécrose aiguë des noyaux gris d'évolution favorable lors d'une encéphalite à mycoplasme.

BACKGROUND: Acute bilateral striatal necrosis complicating the course of a post-infectious encephalitis is rare. CASE REPORT: A previously healthy 5-year-old boy presented with an atypical pneumonia; he rapidly developed, encephalitis revealed by a generalized status epilepticus. After transient improvement, he became confused and mutic, with dystonic postures of his limbs. Painful stimulation resulted in prolonged facial grimacing and doleful cry. CT scan and MRI showed abnormal signals in the whole basal ganglia, typical of bilateral striatal necrosis. Serologic tests for Mycoplasma pneumoniae were positive. The child recovered almost completely. CONCLUSION: A parainfectious process is probably responsible for the transient bilateral striatal necrosis seen in this patient who had Mycoplasma pneumoniae infection several days before the onset of neurologic symptoms. MRI seemed more reliable than CT-scan for the diagnosis of this condition.

[Neonatal hypotonias with congenital disproportion of various types of muscular fiber, especially type I fibers. Demonstration of the familial character of this new entity]. / Hypotonies neon-natales avec disproportion congenitale des differents types de fibre musculaire, et petitesse relative des fibres de type I Demonstration du caractere familial de cette nouvelle entite

Two sisters presenting with benign congenital hypotonia are reported. In both cases the muscle biopsies demonstrated the same pathological pattern, consisting in an abnormal size disproportion between the two main cytoenzymological types of muscle fibers. Their father, exhibiting a slight and diffuse muscle weakness, showed a closely related histological aspect. These three cases bring the first evidence of a familial transmission of this new entity. Its relationship with the other types of "congenital myopathies" is discussed.

[Multifocal tuberculosis in a 15-year-old child]. / Tuberculose multifocale chez un enfant de 15 ans.

We report the case of a 15 year-old boy, presenting with juxta-articular swellings and lacunar skeletal lesions associated with prolonged fever and cachexia. Among the multiple bacteriological samplings, only the trans-osseous puncture of a tibial lacunar lesions, yielded Bacillus tuberculosis. With triple anti-tuberculous chemotherapy, fever and juxta-articular swellings disappeared. However, several articular ankyloses persist, which might need a surgical correction.

[Pseudohypoaldosteronism: familial forms. Eight case-reports, with a review of the literature (author's transl)]. / Pseudo-hypoaldostéronisme: formes familiales. A propos de huit cas et revue de la littérature.

Pseudohypoaldosteronism (PHA) is an uncommon cause of the renal salt loosing syndrome in infancy. The authors describe eight cases in two different families. Hyperaldosteronism persists long after clinical recovery has occurred. Plasma hormone assay allows retrospective recognition of cases overlooked during infancy. This underlines the variability of disease expression among different members of the same family. The high family occurrence rate (over 50%), which is often underestimated, is demonstrated by the study of both families and by a review of published cases. Clinical and biochemical features of familial PHA are discussed. Inheritance is usually on an autosomal dominant basis. However, the small number of reported cases cannot allow any attempt to individualize subgroups of the disorder upon genetic grounds.

[r14 syndrome without major dysmorphism]. / Syndrome r14 sans dysmorphie majeure.

An 8-year-old boy, mentally retarded and epileptic since the age of six months, was found carrier of ring 14 chromosome. A dystrophy of the eye fundi was observed (whitish puncta of the macula); except for the "almond shaped eyes", there was no obvious dismorphism.

[Neonatal pneumococcus laryngitis]. / Laryngite néonatale à pneumocoque.

Report of a case of laryngitis beginning within the first 10 hours of life. The epiglottis was red, swollen, and covered by a membrane. Culture of laryngeal swabs isolated Streptococcus pneumoniae. Complete recovery was obtained with antibiotic therapy.

[A case of botulism in a 11-month-old infant]. / Un cas de botulisme chez un nourrisson de 11 mois.

We report a case of botulism in a 11 month-old infant. Hypotonia complicated by progressive bulbar paralysis revealed the disease. Botulism B toxin was present in serum on the 8th day of the disease. On the occasion of this case report the clinical, diagnostic, epidemiological and pathophysiologic aspects of infant botulism are reviewed. The relationship between sudden infant death and botulism is discussed.

[Ring chromosome 14. II. A case report of r(14) mosaicism. The r(14) phenotype]. / Chromosome 14 en anneau. II. Une observation de r(14) en mosaïque. Le phénotype r(14).

Observation of a patient with r(14) mosaicism together along with 18 previously published observations define the syndrome as follows: mental deficiency, seizures, microcephaly (usually), and facial dysmorphism showing a narrow, elongated face, short palpebral fissures, a flat nasal bridge, and retrognathia. A retinal dystrophia which may be specific of the syndrome consists of a hyperpigmentation and, in three patients, yellow-white spots of the macula. The brain shows mild dilation of the lateral ventricles.

[Acute hepatic insufficiency disclosing congenital syphilis]. / Insuffisance hépatique aiguë révélant une syphilis congénitale.

A breast-fed boy, born to first-cousin parents, had been vomiting since birth; his general condition remained good until age 6 weeks when vomiting became more frequent, and his status suddenly worsened, with polypnea, shock, hypothermia, jaundice, presence of blood in urine, gastric juice, stool, and bleeding tendency during veno-punctures. There was an huge hepatomegaly and a splenomegaly. Hypoglycaemia, metabolic acidosis, severe blood coagulation disturbances, elevated liver enzymes, hypoalbuminemia, pointed to an acute liver failure. He was resuscitated with current supportive measures, and was given a wide spectrum antibiotherapy. Because serologic tests for syphilis were positive in the child and his mother, including the presence of specific IgM the infant was then given Penicillin G therapy only, which resulted in a complete recovery. One month later, a needle liver biopsy showed residual signs of hepatitis. Other possible infectious or metabolic causes of acute liver failure occurring early in life had been excluded.

[Rendu Osler disease revealed by ruptured cerebral arterial aneurysm in an infant]. / Maladie de Rendu-Osler révélée par la rupture d'un anévrysme artériel cérébral chez un nourrisson.

A 6 week-old boy whose mother and sister present with hereditary hemorrhagic telangiectasia (HHT) presented suddenly with listlessness, hypotonia, and acute anemia. Cerebrospinal fluid was grossly hemorrhagic. Brain CT scan was compatible with subarachnoid and intracerebral hemorrhage. Operative investigation diagnosed a ruptured aneurysm of one branch of the right middle cerebral artery. A large clot was removed from the right frontal lobe. The ruptured artery was clipped. Further cerebral and abdominal angiographies did not show other aneurysms. The infant died 18 days later, with bilateral subdural hematoma. The family history and review of the literature suggest that the rupture of a cerebral aneurysm in this infant may have been an early manifestation of HHT. Brain CT scan study seems mandatory in every infant born to a mother with HHT.

Familial aggregation of malignant melanoma/dysplastic naevi and tumours of the nervous system: an original syndrome of tumour proneness.

A five-generation family is here reported in which several members developed malignant melanoma, dysplastic naevi, astrocytoma in all grades, benign or malignant schwannoma, neurofibroma, or meningioma in a single instance. Significant cosegregation of skin and nervous tumours, preclusion of allelism to type 1 neurofibromatosis and phenotypic departure from known syndromes of hereditary proneness to cancer make one suggest an original familial predisposition to both malignant melanoma and central/peripheral nervous tumours.