[Charcot-Marie-Tooth disease associated with periaxin mutations (CMT4F): Clinical, electrophysiological and genetic analysis of 24 patients]. / Maladie de Charcot-Marie-Tooth associée au gène de la périaxine (CMT4F) : description clinique, électrophysiologique et génétique de 24 patients.

Autosomal recessive Charcot-Marie-Tooth disease (AR-CMT) is often characterized by onset in early childhood and severe phenotype compared to the dominant forms. CMT disease associated with periaxin gene (PRX) is rare and characterized by demyelination limited to the major peripheral nerves. Following the discovery of a high frequency of a specific periaxin gene mutation (E1085fsX4 homozygote) in the Reunion Island, we examined all French patients known as carriers of the periaxin gene mutation. There were 24 patients. Eighteen were from the Reunion Island (6 families and 10 sporadic cases). The six remaining patients were in two families, each with two affected individuals, and two sporadic cases. The series included 17 female and seven male patients. Walking was acquired late, on average at 3.4±1.6 years. One patient never learned to walk. The Charcot Marie Tooth Neuropathy Score (CMTNS) averaged 24.5±8.1. Seven patients had been wheelchair-bound since the age of 24±22. Other symptoms were: scoliosis most often observed after the age of 12 years and sometimes complicated by a restrictive respiratory syndrome; foot deformity in 24 patients; strabismus; glaucoma; myopia. When conduction recordings are available, median nerve motor conduction was slow (<10m/s), associated with a major lengthening of distal latencies. Study of the periaxin gene should be considered in patients with severe demyelinating neuropathy associated with early infantile scoliosis. This disease leads to major disability (29% of patients in this series were wheelchair-bound) and to respiratory insufficiency. Genetic counselling is highly recommended for consanguineous families.

[The messenger syndrome]. / Le syndrome du messager.

Since mid 2005 pediatricians of the Groupe hospitalier Sud Reunion de Saint-Pierre have observed a self-imposed requirement to test for mother-to-child transmission of chikungunya. Sanitary authorities refuse to consider such testing as necessary. The risk of mother-to-child transmission was not mentioned in literature of the time.

[Study of 178 ante partum deaths in 2001-2004 in the southern part of Reunion Island]. / Etude des 178 morts foetales in utero dans le sud de l'île de la Réunion en 2001-2004.

INTRODUCTION: The perinatal mortality rate is 18.5 in the southern part of the Reunion Island (Indian Ocean), of which 2/3 are due to antepartum fetal deaths (APFD). METHODS: During a 4-year period (2001-2004) all APFD from 22 weeks gestation were recorded and analyzed with placental histology, bacteriological samples and autopsies in 27% of cases. The Australasian and New-Zealand classification PSANZ-PDC (2000) was used. Risk factors of fetal death with monofetal pregnancies are determined in comparison with live births. RESULTS: Out of 21.495 total births, 178 APFD were recorded. The main obstetrical risk factors were primiparity (OR 1.6, p = 0.002), maternal age over 34 years (OR 1.6, p = 0.01), hypertensive disorders of pregnancy (OR 3.0, p < .001) and multiple births (OR 2.5, p < 0.001). The great majority of APFD (76%) involved preterm fetuses, of which 61% of very preterm (<33 weeks), and 25% of fetuses were growth retarded (OR 3.9, p < 0.001). Only 8% of cases were considered unexplained. The main etiologies were infectious causes in 26% of cases, vascular fetal growth restriction (18%), specific perinatal conditions (14%) of which one-third were due to cord anomalies, preeclampsia (10%), maternal conditions (8%), congenital anomalies (8%) and ante-partum hemorrhage (7%). We discuss the interests and the limitations of using the Australian and New-Zealand classification PSANZ 2000. Intra-uterine growth retardation is one of the principal risk factors of fetal death. CONCLUSION: Besides well-known obstetrical risk factors such as diabetes, hypertension, multiple pregnancies, all screening of intra-uterine growth retardation in the second trimester of pregnancy should include a special survey in order to minimize the incidence of APFDs.

[Chikungunya infection in pregnancy: Evidence for intrauterine infection in pregnant women and vertical transmission in the parturient. Survey of the Reunion Island outbreak]. / Infection à Chikungunya chez la femme enceinte et risque de transmission materno-foetale.

PURPOSE: Since February 2005, an outbreak of Chikungunya virus (CHIKV) infections occurred in Reunion Island. It is transmitted by the Aedes albopictus mosquito. Neonatal cases observations suggest possible fetal transmission during pregnancy. MATERIAL [corrected] AND METHODS. Observations made in 160 pregnant mothers infected by CHIKV between June 1, 2005 and February 28, 2006, in the south of Reunion island were recorded. RESULTS: Three of nine miscarriages before 22 weeks of gestation could be attributed to the virus. 3,829 births took place during this time. Among the 151 infected women, 118 were viremia negative at delivery, and none of the newborns showed any damage. Among the 33 with positive viremia at delivery, 16 newborns (48.5%) presented neonatal Chikungunya. DISCUSSION: Though fetal contamination risks appear to be rare before 22 weeks of gestation, they are potentially dangerous. After 22 weeks gestation, newborns infection occurs if the mother is viremia positive at delivery. Transplacental transmission is suspected, but the pathogenic mechanism remains unknown.

[Herpetic neonatal hepatitis]. / Les hépatites herpétiques néonatales.

Herpes simplex virus (HSV) infection can affect various organs-systems in the neonatal period. Herpetic hepatitis was seldom reported in the literature. We report on 2 cases. Firstly, a 16 day-old newborn infant was admitted because of haemorrhagic syndrome and shock. Biological assessment showed a severe hepatic insufficiency. Antibiotic and aciclovir therapy was started as HSV infection was suspected. Five days later, the herpetic attack was confirmed by polymerase chain reaction (PCR) in blood and cerebrospinal fluid (CSF). The genotye of the virus in the CSF was HSV1. Treatment included aciclovir for 21 days intravenously and 2 months orally. At 10 months, the clinical and biological examinations were normal. Secondly, a 4 day-old newborn was hospitalised because of fever and polypnea. Pulmonary X rays showed heterogeneous opacities of the right base. Serum C reactive protein was 30 mg/l. Antibiotic therapy was started. Two days later, the fever persisted while a severe hepatic insufficiency developed. The diagnosis of herpetic hepatitis was evoked and the child was given aciclovir. Forty-eight hours later, the PCR confirmed a HSV in blood, while viral culture of a mouth swab found HSV 2. Evolution was favourable after 21 days of specific and symptomatic treatment. Aciclovir treatment was continued orally for six months. Herpetic hepatitis is rare in the neonatal period. Diagnosis must be evoked early when facing severe neonatal hepatic insufficiency. Provided specific treatment, prognosis is good.

[Congenital varicella: limits of prenatal diagnosis]. / La varicelle congénitale: les limites du diagnostic prénatal.

INTRODUCTION: Primary varicella infection during pregnancy is uncommon. Fetal varicella syndrome is unusual when varicella occurs after 20 weeks of gestation. CASE REPORT: A mother contracted chicken pox at 21 weeks and 3 days of gestation. Monthly monitoring was assured by the center for prenatal diagnosis, starting from 23 weeks. At 36 weeks, foetal echography detected liver calcifications, without other lesions. At 38 weeks, the patient went into spontaneous labour and delivered a male baby. The baby presented cicatricial skin lesions all over the body and scalp. The cerebral scan detected calcifications and a bilateral chorioretinitis was noticed. At 12 months, the infant had delayed psychomotor acquisitions, a cerebral cortical atrophy and blindness. CONCLUSION: The presence of fetal liver calcifications after chicken pox in the mother is a seldom reported sign. In our observation, liver calcifications were the single sign of a severe fetal damage.

[Post mortem brain MRI: an alternative for pathology examination in Bourneville tuberous sclerosis of the fetus?]. / IRM cérébrale post mortem: une substitution à l'examen anatomo-pathologique dans la sclérose tubéreuse de Bourneville du foetus?

Antenatal discovery of cardiac rhabdomyomes evokes the diagnosis of Bourneville's disease. Antenatal brain exploration with ultrasonography and magnetic resonance imaging (MRI) can highlight cerebral localizations. In the event of termination of pregnancy, confirmation of the cerebral lesions can be achieved with post mortem MRI as well as pathology examination. MRI can be usefully employed in the event pathology examination is not feasible.

[Maternal toxoplasmosis before conception and chorioretinitis in twin sisters]. / Toxoplasmose maternelle anté-conceptionnelle et choriorétinite chez des jumelles.

A maternal toxoplasmosis before conception is exceptionally transmitted to the fetus. We report an observation of twin sisters who presented congenital toxoplasmosis with chorioretinitis detected at nine months of age. The anamnesis revealed that the mother had had toxoplasmosis one month before conception. In the event of preconceptual infections, we propose fetal ultrasonography, histological examination of the placenta at delivery, as well as a pediatric follow-up of the infants (serological samples every month, cranial ultrasonography, fundus oculi).

[Clinical aspects and genetic specificities of cystic fibrosis in Reunion Island]. / Aspects cliniques et spécificités génétiques de la mucoviscidose à l'île de la Réunion.

OBJECTIVES: Evaluation of the phenotype-genotype correlation of a specific mucoviscidosis mutation, "Y122X", in Reunion Island. This mutation represents 25% of our cases. PATIENTS AND METHODS: Retrospective study of a cohort of 84 children presenting cystic fibrosis (CF) during a 5-year period (1994-1998). Diagnosis was based on one or two identified genetic mutations and/or minimum two abnormal chloride sweat tests (Cl > 70 mmol/l). Follow-up of this cohort was performed in the two referral centers of the Island following the French national guidelines (INSERM U 155). RESULTS: In our population, we identified 10 mutations, of which three of them represented more than 80% of the cases: Delta F508 (51.8%), Y122X (24.4%) and 3120 + 1G --> A (4.8%). The authors report clinical significant differences in children with the homozygote mutation Y122X as compared with children presenting the Delta F508 CF-mutation: failure to thrive affecting mainly the height with, paradoxically, a relatively normal weight development, and a better pulmonary function. CONCLUSION: The frequent Y122X CF-mutation reported in "la Reunion" seems to affect mainly height in children with a relatively good nutritional outcome. This failure to thrive does not seem to be of digestive origin. These results suggest that growth gene(s) located nearby the cystic fibrosis transmembrane conductance regulator (CFTR) may have suffered the same segregation than the Y122X mutation or that clusters of this specific Caucasian population known as "petits blancs" in la Reunion are smallest for ethnic reasons.

[Severe cytomegalic inclusions disease in the fetus of a woman immunized before pregnancy]. / Maladie des inclusions cytomégaliques sévères chez le foetus d'une femme immunisée avant la grossesse.

After detection of a fetal microcephaly at 24 weeks gestation, we performed an amniocentesis at 29 weeks with chromosomal and polymerase chain reaction (PCR) search for viral contamination. Cytomegalovirus (CMV) infection was confirmed by PCR although the mother had previously been tested as immunized for CMV prior to conception. Abortion was induced; the fetus presented clinical CMV injuries confirmed by positive tissue culture (liver, brain and lungs). Recent publications have reported similar observations with variable viral strains. These findings point out the importance attentive search for ultrasonographic signs suggestive of fetal CMV infection.

[Clinical study and prevalence of fetal alcohol syndrome in medico-social institutions of the Reunion Island]. / Etude clinique et prévalence du syndrome d'alcoolisation foetale pris en charge dans les établissements médicosociaux de l'île de la Réunion.

BACKGROUND: Fetal alcohol syndrome (FAS) is a major problem in the Reunion Island and the Public Health Authorities decided to determine its prevalence in their medico-social centers on 31 December 1996. MATERIAL AND METHODS: A questionnaire was established to identify affected patients in the 20 medico-social centers in charge of 1320 children. Eighty-eight children were selected and 87 could be analyzed. RESULTS: Sixty-four of 87 (76.3%) were FAS and 23 of 87 (23.7%) had closely alcohol-related diseases. The prevalence was between 7.1 and 14.1% and lower than expected from available data. CONCLUSION: The study allowed to precise the social and familial factors predisposing to alcohol addiction during pregnancy. A TV prevention message will be broadcasted after this study.

Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution.

We describe an 18-year-old patient with psychomotor retardation and abnormally short metatarsi and metacarpals but no other signs of classic Refsum disease. Molecular analysis of the phytanoyl-coenzyme A hydroxylase gene revealed a homozygous deletion causing a frameshift. Surprisingly, L-pipecolic acid was elevated in plasma, and microscopy of the liver showed a reduced number of peroxisomes per cell and a larger average peroxisome size. These abnormal peroxisomes lacked catalase as did peroxisomes in fibroblasts of this patient. Such generalized peroxisomal abnormalities are not present in classic Refsum disease.

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. One nonsense and six different novel frameshift mutations, all located in the second exon, were identified. Together with the previously reported mutations [Kohlhase et al., 1999], they establish that TBS results from haploinsufficiency. The finding of de novo mutations in the sporadic cases is consistent with the proposed complete penetrance of the disease. Moreover, the occurrence of the same 826C>T transition in a CG dimer, in three sporadic cases from the present series and three sporadic cases from the other series [Kohlhase et al., 1999] (i.e., six of the eight mutations identified in sporadic cases), reveals the existence of a mutation hotspot. Six different SALL1 polymorphisms were identified in the course of the present study, three of which are clustered in a particular region of the gene that encodes a stretch of serine residues. Finally, the chromosome 16 breakpoint of a t(5;16)(p15.3;q12.1) translocation carried by a TBS-affected individual was mapped at least 180 kb telomeric to SALL1, thus indicating that a position effect underlies the disease in this individual.

[Severe anorexia in infants in Reunion: a new autosomal recessive disease?]. / L'anorexie sévère du nourrisson réunionnais: une nouvelle affection autosomique récessive?

BACKGROUND: Infantile anorexia is usually considered as a psychogenic disorder with benign prognosis. However, unusually severe characteristics of infantile anorexia, seen in the south of the island, seem to us in favor of a new metabolic etiology. POPULATION AND METHODS: Among 38 known cases, we retrospectively studied the best documented observations of 24 children admitted over the last 25 years to our institution. RESULTS: The sex ratio was ten females and 14 males. Twenty-three of the 24 infants lived in formerly isolated localities of the island where other hereditary diseases have been observed with an unusually high frequency. The family pedigrees favoured an autosomal recessive heredity. Severe anorexia, accompanied by irrepressible vomiting (91%), appeared at the age of 8.5 months +/- 3.5. Parenteral (54.2%) or enteral (54.2%) feeding was necessary but did not always avoid death, which occurred in 45.8% of the cases at the age of 24 months +/- 3.5. All of the children which survived had neurological disorders (pyramidal syndrome, ataxia, laryngeal palsy, mental retardation, seizures) which occurred sometimes at an early stage. The investigations did not allow the identification of any known cause. DISCUSSION: The elevated level of lactic acid in the cerebral spinal fluid seemed to indicate a possible mitochondrial disorder, eventually a mutation of an autosomal gene of the pyruvate dehydrogenase complex because of the normal lactate/pyruvate ratio, but enzymatic activities were normal. The cerebral MRI showed features of leukodystrophy. On the other hand, the elevated level of plasma serotonin seemed to indicate a disorder of the serotonin metabolism, for which an animal model exists. CONCLUSION: We propose to name this new syndrome by the acronym 'RAVINE' which associates Reunion, Anorexia, Vomiting which is Irrepressible, and Neurological signs. Linkage study might allow the localization and isolation of a gene and allow one to start understanding the biological mechanism which we suspect to be an hereditary neurobiological eating disorder.