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D Fontan

Publications and source records attributed to D Fontan.

At least 19 recordsLinked to original sources
PubMed2001

[Cerebellar vermis hypoplasia with extracerebral involvement (retina, kidney, liver): difficult to classify syndromes].

UNLABELLED: Congenital cerebellar vermis hypoplasias diversely associated with retinopathy, nephropathy and hepatopathy are rare syndromes of uncertain nosology. We report three new cases. CASE REPORTS: Case 1. A 3-month-old boy presented a brief nystagmus. At the age of 2 years, he had facial dysmorphia, hypotonia, ataxia, ocular motor apraxia and neurodevelopmental impairment with cerebellar vermis hypoplasia. The electroretinogram showed asymptomatic retinal involvement. At the age of 6 years, he developed chronic renal failure. The diagnosis of familial juvenile nephronophthisis was made by detection of a large homozygous deletion of the NPH1 region. Case 2. A term newborn boy presented apnea, tachypnea, hypotonia, nystagmus, ptosis, lack of visual contact and hepatomegaly. He had facial dysmorphia, bilateral optic coloboma with chorioretinal dysplasia and cerebellar vermis hypoplasia. There were cysts in the kidneys with increased echogenicity and lack of demarcation between the pyramids and the cortex. The liver was hyperechoic with fibrosis. At the age of 15 months, the child had severe developmental delay. He had bouts of fever. A search for a large homozygous deletion of the NPH1 region was negative. Case 3. A term newborn girl presented difficulty to suck, cyanosis, hypotonia and ptosis. Later, the child had a developmental delay. At the age of 6 years, she developed chronic renal failure (nephronophthisis). At the age of 23 years, she presented divergent strabismus, ataxia, mental retardation, slow ocular pursuit and facial dysmorphia. The neuroimaging showed a cerebellar vermis hypoplasia. A search for a large homozygous deletion of the NPH1 region was negative. CONCLUSION: The diagnosis of cerebellar vermis hypoplasia requires searching for retina, kidney and liver involvement. The large homozygous deletion of the NPH1 region has to be investigated if typical familial juvenile nephronophthisis is associated. Because cerebellar vermis hypoplasia with extracerebral involvements (retina, kidney, liver) is part of many different closely related syndromes, a clear molecular classification is necessary for accurate genetic counselling and an early prenatal diagnosis.

Abnormalities, Multiple↗
PubMed2001

X-linked myopathy with excessive autophagy: a clinicopathological study of five new families.

In 1988, Kalimo et al. (Ann Neurol 23 (1988) 258)described a new type of X-linked myopathy in a Finnish family. The clinical course was characterized by slow progression of muscle weakness without loss of ambulation in childhood and no evidence of cardiac, respiratory, or central nervous system involvement. Muscle fibers were not necrotic and showed excessive autophagic activity and exocytosis of the phagocytosed material. These authors proposed the name X-linked myopathy with excessive autophagy. Subsequently, only one French family has been reported with similar clinical and histopathological data. We report here five new families with a total of eight affected boys with the same clinical and histopathological features as reported in the original families. Histopathological findings of an asymptomatic mother are also reported. Vacuolar changes in muscle fibers result both from invaginations of the sarcolemma along with a variable component of basal lamina and from an autophagic process. The complement C5b-9 membrane attack complex associated with MHC class 1 antigen and calcium deposits is involved in muscle fiber damage. Among the X-linked myopathies, the identification of this new type is of great interest because of its favorable prognosis and unique morphological findings.

Adolescent↗
PubMed2000

Schizencephaly: clinical and imaging features in 30 infantile cases.

Schizencephaly is an uncommon structural disorder of cerebral cortical development, characterized by congenital clefts spanning the cerebral hemispheres from the pial surface to the lateral ventricles and lined by cortical gray matter. Either an antenatal environmental incident or a genetic origin could be responsible for this lesion which occurs between the third and fourth month of gestation. We report the clinical and cranial imaging features of 30 children, of whom 15 had unilateral and 15 had bilateral lesions. Their ages at the time of the first presentation ranged from 1 month to 10 years. They were thoroughly studied from clinical, epileptical, imaging and electroencephalographic (EEG) viewpoints. Five patients were investigated by cranial computed tomography (CT), eight by cranial magnetic resonance (MR) imaging, and 17 by both methods. The clinical features consisted of mild hemiparesis in 17 cases (57%), 12/17 were related to a unilateral phenotype (80% of all unilateral forms) and 5/17 to a bilateral phenotype. A tetraparesis was present in nine cases, all of which were due to a bilateral cleft. Bilateral forms were significantly associated with tetraparesis, whereas unilateral forms were associated with hemiparesis. Mental retardation was observed in 17 cases (57%), and was observed significantly more often in bilateral clefts (80%). When both hemispheres are involved, an absence of reorganization of the brain function between the two hemispheres leads to severe mental deficits, in addition to the cerebral anomaly itself. Eleven patients had seizures (seven from unilateral and three from bilateral forms). The degree of malformation was not related to the severity of epilepsy. Migration disorders, such as dysplasia or heterotopia, were observed in 30% of cases and are also important etiopathogenetic factors. The septum pellucidum was absent in 13 cases (43%), with septo-optical dysplasia in two cases. Corpus callosum dysgenesis was noted in 30% of cases. Four cases of mega cisterna magna were noted. Although familial cases and environmental factors have been previously reported, schizencephaly appears to be, in the majority of cases, sporadic.

Adolescent↗
PubMed2000

Multi-minicore disease--searching for boundaries: phenotype analysis of 38 cases.

Multi-minicore disease (MmD) is a congenital myopathy morphologically defined by the presence of multiple small zones of sarcomeric disorganization and lack of oxidative activity ("minicores") in muscle fibers. The dinical expression of MmD is considered to be greatly variable, and the morphological lesions are nonspecific; therefore, its boundaries are poorly defined, and its molecular bases are not known. To better define the phenotypic characteristics of MmD, we analyzed a large series of 38 patients with multiple minicores in muscle fibers in the absence of any other potential cause. According to clinical features, 4 subgroups were identified. Most patients (30 cases) shared a common highly consistent phenotype marked by the axial predominance of muscle weakness and a high occurrence of severe respiratory insufficiency and scoliosis ("classical" form). Other forms were characterized by pharyngolaryngeal involvement and total lack of head control (2 cases), antenatal onset with arthrogryposis (3 cases), and slowly progressive weakness with marked hand amyotrophy (3 cases). Type 1 fiber predominance and hypotrophy as well as centrally located nuclei were found in every subgroup. MmD is thus phenotypically heterogeneous, but a typical recognizable phenotype does exist. This phenotype classification should be helpful when undertaking research into the molecular defects that cause MmD.

Biopsy↗
PubMed1999

Sjögren-Larsson syndrome: early diagnosis, dietary management and biochemical studies in two cases.

BACKGROUND: Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder with worldwide distribution. It consists of ichthyosis, spastic diplegia and mental retardation caused by an enzymatic defect in fatty alcohol oxidation. OBJECTIVE: To study the effects of dietary management on clinical outcome and plasma/red blood cell fatty alcohol and plasmalogen concentrations. METHODS: To reduce fatty alcohol production, we reduced total fat intake to 30% of total intake of calories. To correct d 6 desaturase deficiency, we supplemented the diet with both n-3 and n-6 fatty acids to obtain a linoleic/linolenic acid ratio of 6 with low erucic acid rapeseed oil, plus high unsaturated fatty acids. We used gas liquid chromatography to assay blood cell membranes and plasma fatty alcohols/plasmalogens. RESULTS: Two SLS infants with proven fatty alcohol/NAD+ oxidoreductase deficiency were studied. Good clinical results were obtained in one of the patients when dietary intervention was started in early infancy and correlated well with plasma fatty alcohol decrease. However, no clinical improvement was seen in the other patient who started later with low compliance. Acitretin therapy was necessary to control skin symptoms in this second patient. CONCLUSION: Dietary intervention using the combined approach described here may improve fatty alcohol metabolism in SLS. However, only very early intervention seems clinically beneficial.

Alcohol Oxidoreductases↗
PubMed1998

Congenital cutaneous defects as complications in surviving co-twins. Aplasia cutis congenita and neonatal volkmann ischemic contracture of the forearm.

BACKGROUND: During twin pregnancies, several complications may result in the death of a co-twin depending on the date of death. We describe herein 2 infant survivors of monozygotic twin pairs with 2 distinct possible complications: a aplasia cutis congenita and Volkmann ischemic contracture. OBSERVATIONS: One infant had extensive aplasia cutis congenita with an associated monozygotic co-twin who died at 3 months of gestation, and the other child had a localized arm defect due to Volkmann ischemic contracture and brain damage, with a co-twin who died at approximately 6 weeks of gestation. CONCLUSIONS: Congenital cutaneous defects may result in the death of a co-twin. The most common of these defects is aplasia cutis congenita associated with a fetus papyraceus or a dead fetus related to ischemic/thrombotic events in the placenta and fetus. Volkmann ischemic contracture is rare in the newborn but can cause neonatal cutaneous defects. The cause of Volkmann ischemic contracture in newborns is unknown; however, our second observation suggests the possible role of a dead fetus.

Compartment Syndromes↗
PubMed1998

[Facioscapulohumeral myopathy and germinal mosaicism].

BACKGROUND: Germline mosaicism is now well known to account for recurrence of hereditary human disorders. Facioscapulohumeral muscular dystrophy is an autosomal dominant disorder; its locus has been identified in the telomeric region of chromosome 4 at the q35 band. It appears to have a high rate of mutation. CASE REPORT: A young girl had presented from childhood signs of a severe form of facioscapulohumeral muscular dystrophy, but with no familial history. The diagnosis was ultimately confirmed at the age of 23 years by molecular studies evidencing the deletion. The same abnormality was sparsely found in the child's father who appeared to harbor the mutation as a germline mosaicism with no clinical expression. CONCLUSION: This case illustrates the possibility of severe facioscapulohumeral muscular dystrophy and the dominant transmission of the disorder which may be clinically occult. It underlines the importance of molecular biology and the difficulties of genetic counselling.

Adolescent↗
PubMed1998

Congenital insensitivity to pain with anhydrosis. Report of two unrelated cases.

Two unrelated female cases of congenital insensitivity to pain with anhydrosis are presented. The first case was born from consanguineous parents. In both cases, onset of manifestation was observed in infancy with automutilation and recurrent fever. Both were mentally retarded. They underwent a peripheral nerve biopsy respectively at 3 and 33 years. A dramatic loss of unmyelinated fibers was observed in both cases. Myelinated fibers were also moderately reduced in number, especially those of smallest diameter; this loss was more marked in the second patient who was adult when the peripheral nerve was studied. Clusters of regenerating myelinated fibers were seen in both cases. Such histological observations might suggest a slowly progressive disorder. The cases are discussed together with previous reports dealing with congenital insensitivity to pain.

Adult↗
PubMed1997

Biochemical and genetic studies of four patients with pyruvate dehydrogenase E1 alpha deficiency.

We report studies of four patients with pyruvate dehydrogenase complex (PDH) deficiency caused by mutations in the E1 alpha subunit. Two unrelated male patients presented with Leigh syndrome and a R263G missense mutation in exon 8. This mutation has previously been described in males with the same phenotype. The two other patients had different novel mutations: (1) an 8-bp deletion at the C-terminus (exon 11) was found in one allele of a young girl suffering from microcephaly and (2) a C88S missense mutation (exon 3) in a boy who only presented with motor neuropathy. These mutations were not found in the mothers of any of the four cases. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in three out of the four patients. These findings confirm that: (1) PDH deficiencies are genetically heterogeneous, (2) the R263G mutation is more frequent in male cases than are other mutations and this amino acid is a hot spot for gene mutations, (3) the last eight amino acids may be important for the conformation of the tetrameric E1-PDH enzyme, and (4) the amino acids at positions 88, 263 and 382-387 are essential for the linking of the alpha subunit with the beta subunit and for the activity of the holoenzyme.

Adolescent↗
PubMed1997

Collaborative study of mosaic tetrasomy 12p or Pallister-Killian syndrome (nineteen fetuses or children).

The difficulties in the diagnosis of Pallister-Killian syndrome are illustrated in this study of nineteen fetuses and children. Diagnosis based on clinical appearance alone is often difficult due to the broad spectrum of clinical anomalies not specific to this syndrome. Due to mosaicism, it is altogether necessary to examine several tissues for the presence of tetrasomy 12p, including circulating lymphocytes in which mosaicism can be as low as 1-3%, amniocytes, chorionic cells and skin fibro-blasts in which mosaicism ranges from 6-100%. When highly suspected on ultrasound examination, the diagnosis recommends prenatal cytogenetic studies because survivors are severely mentally retarded. All the cases are sporadic with only a single preliminary report of recurrence. The cytogenetic diagnosis is therefore helpful in order to reassure family members in regard to genetic counseling.

Abnormalities, Multiple↗
PubMed1996

[Superior sagittal sinus thrombosis in children during the first year of life: clinical aspects, imaging and development].

BACKGROUND: Thrombosis of the intracranial sinuses and veins may be septic or aseptic, and in the latter case are often due to alteration in hemodynamics. It may also be seen in young babies without known predisposing factors. PATIENTS: From 1988 to 1994, 11 children had cerebral venous thrombosis (longitudinal sinus) in the first year of their life. Their ages ranged from two days to 11 months. Transient seizures, lethargy, pseudo tumor cerebri were the first clinical symptoms. The presence of longitudinal sinus thrombosis was suggested by unenhanced CT scan, confirmed by colour doppler flow imaging and magnetic resonance angiography, with absence of blood flow in the longitudinal sinus. Repeated doppler flow imaging showed thrombus resolution within 3 weeks. Thrombosis was associated with predisposing factors in seven cases and appeared idiopathic in the four others. CONCLUSION: Diagnosis of longitudinal sinus thrombosis can be made more accurately and noninvasively by colour doppler flow and angio-MRI. Treatment with anticoagulants appears unnecessary and dangerous in idiopathic forms.

Female↗
PubMed1996

[Schizencephaly and upper limb malformation].

BACKGROUND: Schizencephaly, a failure of the cerebral mantle to form is usually unilateral and not associated with anomalies of the controlateral limbs. We present two cases associated with such anomalies. CASE REPORTS: Case no 1. A boy born with a lobster claw deformity in the right arm. His IQ was 60 and he developed generalized seizures at the age of 4 years with spastic diplegia. MRI examination showed unilateral left schizencephaly also lined with pachygyric cortex. Case no 2. A girl was born with a right ectromelic-hand and developed left spastic hemiparesy. Her IQ was normal. She had a generalized seizure at the age of 11 years. MRI showed unilateral right schizencephaly also lined with pachygyric cortex and heterotopic periventricular gray matter. DISCUSSION: Schizencephaly seems to be due to localized ischemia in the periventricular germinal matrix during the 7th week of gestation. The limb deformity could be explained by the same vascular mechanism in the first case but not in the second one since it was homolateral to brain damage. CONCLUSION: Description of further cases is necessary to understand this association. We suggest MRI examination of brain in patients with limb deformity associated with neurological damage.

Abnormalities, Multiple↗
PubMed1995

Surgical treatment of an early epileptic encephalopathy with suppression-bursts and focal cortical dysplasia.

A case of early epileptic encephalopathy (EIEE) with suppression-bursts or Ohtahara's syndrome, associated with focal cortical dysplasia is reported. Infantile spasms and brief tonic unilateral seizures began on the fifth day of life. Interictal EEG demonstrated an asymmetrical "suppression-burst" pattern with no wake or sleep cycling. Seizures were refractory to all antiepileptic drug (AED) and steroid therapy. Magnetic resonance imaging (MRI) showed right frontotemporal cortical thickening. After three weeks of an ineffective medical treatment a preoperative evaluation with single photon emission computed tomography (SPECT) and electrocorticography (ECoG) was performed to characterize epileptogenic focus. Surgical resection of the precentral area was performed at age 1 month. Neuropathologic examinations confirmed diagnosis of focal cortical dysplasia by identifying cytoarchitectural disarray and ectopic neurons located deep in subcortical white matter. During follow-up, 1-year postoperative the child had a single febrile seizure. Neurologic examination showed minor developmental delay and slight left-sided weakness.

Age Factors↗
PubMed1995

Phenotypic variability in van der Woude syndrome.

The association of lower lip pits with cleft lip and/or palate defines the van der Woude syndrome (VWS). VWS has an autosomal dominant mode of inheritance wiht a high penetrance and a variable expression. A gene involved in the origin of VWS is linked to loci on chromosome 1q32-q41. The gene might be involved in the programmed cell death of neural crest derived cells. Other malformations have been associated with the syndrome (dental defects, syngnathia, limb abnormalities, popliteal webs...). We report 4 cases with VWS demonstrating the wide clinical variability. One case shows brain abnormalities that might be part of the clinical spectrum of VWS.

Abnormalities, Multiple↗
PubMed1994

Skewed inactivation of an X chromosome deleted at the dystrophin gene in an asymptomatic mother and her affected daughter.

A girl with severe Becker muscular dystrophy and apparently normal chromosomes had a heterozygous deletion for exons 51, 52, and 53 of the dystrophin gene. This deletion was transmitted by her mother, who was unaffected. To differentiate the normal and the deleted X chromosomes, fluorescence in situ hybridization (FISH) was applied to metaphase chromosomes, using probes for both exons 51 and 52, which are only 388 and 113 base pairs long, respectively. FISH signals were observed in one or both chromatids of one chromosome, but never on both chromosomes, suggesting the lack of hybridization on the deleted X chromosome. Using 5-bromodeoxyuridine incorporation to differentiate the late (inactive) and the early replicating (active) X chromosomes, 77% of the signals were observed on the active X chromosomes in the mother. This percentage was only 18% in the daughter, suggesting that skewed inactivation of the X chromosomes was responsible for the phenotypic differences.

Adolescent↗