Showing papers by "Alain Verloes published in 2008"

RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders.

Abstract: Joubert syndrome-related disorders (JSRDs) are autosomal recessive pleiotropic conditions sharing a peculiar cerebellar and brainstem malformation known as the 'molar tooth sign' (MTS). Recently, mutations in a novel ciliary gene, RPGRIP1L, have been shown to cause both JSRDs and Meckel-Gruber syndrome. We searched for RPGRIP1L mutations in 120 patients with proven MTS and phenotypes representative of all JSRD clinical subgroups. Two homozygous mutations, the previously reported p.T615P in exon 15 and the novel c.2268_2269delA in exon 16, were detected in 2 of 16 families with cerebello-renal presentation ( approximately 12%). Conversely, no pathogenic changes were found in patients with other JSRD phenotypes, suggesting that RPGRIP1L mutations are largely confined to the cerebello-renal subgroup, while they overall represent a rare cause of JSRD (<2%).

Spectrum of epilepsy in terminal 1p36 deletion syndrome.

Abstract: Summary Purpose: Previous reports have summarized the seizures types occurring in 1p36 deletion syndrome. To better define the spectrum of epilepsy, we studied 91 patients (median age 7.8 years) with confirmed 1p36 deletion. Methods: Based on clinical charts, we retrospectively analyzed the evolution of both the EEG findings and seizures. Results: Epilepsy occurred in 53 patients (58.2%), with onset at a median 2.75 months. First seizures were generalized tonic (8 cases), tonic and clonic (6) or myoclonic (12), simple partial (6), or complex partial (14). Thereafter, 20 patients (21.9%) developed infantile spasms with hypsarrhythmia, at a median age of 5 months. High doses of oral steroids were tried in nine cases, with a prompt remission of seizures in six. Among them, five were seizure-free at the time of evaluation. Conversely, two of three nonresponders to steroids developed severe and refractory epilepsy. At the time of evaluation, 32 patients were seizure-free, from a median age of 1.8 years. Nineteen patients (20.9%) had developed refractory epilepsy with polymorphic seizures, including generalized tonic and tonic–clonic seizures (13) combined with myoclonic seizures (11) and atypical absences (3), atonic seizures (2), or complex partial seizures (3). The EEG showed focal, multifocal or generalized spikes, polyspike, and waves, with poverty of the usual background rhythmic activities. Conclusions: Early epilepsy is a frequent finding in 1p36 deletion syndrome with infantile spasms as of the most common features that can contribute to a poor clinical outcome. Early diagnosis and management of infantile spasm in this condition is mandatory.

Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome

Abstract: Noonan syndrome (NS) and cardio-facio-cutaneous (CFC) syndrome are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation. There is a significant clinical overlap between NS and CFC syndrome, but ectodermal abnormalities and mental retardation are more frequent in CFC syndrome. Mutations in PTPN11 and KRAS have been identified in patients with NS and those in KRAS, BRAF and MAP2K1/2 have been identified in patients with CFC syndrome, establishing a new role of the RAS/MAPK pathway in human development. Recently, mutations in the son of sevenless gene (SOS1) have also been identified in patients with NS. To clarify the clinical spectrum of patients with SOS1 mutations, we analyzed 24 patients with NS, including 3 patients in a three-generation family, and 30 patients with CFC syndrome without PTPN11, KRAS, HRAS, BRAF, and MAP2K1/2 (MEK1/2) mutations. We identified two SOS1 mutations in four NS patients, including three patients in the above-mentioned three-generation family. In the patients with a CFC phenotype, three mutations, including a novel three amino-acid insertion, were identified in one CFC patient and two patients with both NS and CFC phenotypes. These three patients exhibited ectodermal abnormalities, such as curly hair, sparse eyebrows, and dry skin, and two of them showed mental retardation. Our results suggest that patients with SOS1 mutations range from NS to CFC syndrome.

Coffin-Lowry syndrome: a multicenter study.

Abstract: The Coffin-Lowry syndrome is an inherited syndrome of mental retardation, characteristic facies and skeletal anomalies. The occurrence of severe manifestations in males, with no instance of male-to-male transmission, suggests an X-linked inheritance. The paper describes seven families from five European Centers.

3C syndrome: third occurrence of cranio-cerebello-cardiac dysplasia (Ritscher-Schinzel syndrome)

Abstract: We report a child with an unusual pattern of malformations: severe delay in bone maturation, wide fontanelles and facial dysmorphism (evoking cleidocranial dysplasia), relative macroencephaly with cerebellar vermis hypoplasia, hypertelorism, skeletal abnormalities (1st ribs aplasia, multifocal sternal ossification centers, thin bones), septal defect, muscular waste, hypotonia and developmental delay. Most of these features have been reported previously by Ritscher, Schinzel et al. in two sibs, who suffered more severe cerebellar malformations (Dandy-Walker cyst or vermis aplasia). We propose 3C syndrome as an easy acronym for this Cranio-Cerebello-Cardiac dysplasia.

Molecular cytogenetic characterization of terminal 14q32 deletions in two children with an abnormal phenotype and corpus callosum hypoplasia

Abstract: Among previously reported cases of 14q terminal deletions, only 11 have dealt with pure terminal deletion of 14q (14q3-14qter) and the break points were mapped by fluorescent in situ hybridisation (FISH) or genotyping in only four of them. Thanks to a collaborative study on behalf of the 'Association des Cytogeneticiens de langue Francaise'(ACLF), we report two patients with terminal deletion of the long arm of chromosome 14, del(14)(q32.2) and del(14)(q32.32), diagnosed by subtelomere screening. In the two cases, a thick nuchal skinfold was detected by early ultrasound with normal prenatal karyotype. Their postnatal phenotype included large forehead, narrow palpebral fissures, epicanthic folds, upturned tip of the nose, narrow mouth and thin upper lip, microretrognathia, prominent earlobes, hypotonia, delayed psychomotor development and hypoplastic corpus callosum. By physical mapping using FISH, the size of the deletions was measured for patients 1 and 2: 6.55+/-1.05 and 4.67+/-0.10 Mb, respectively. The paternal origin of the deleted chromosome 14 was established by genotyping of microsatellites for patient 1 and the phenotype of terminal del(14)(q32) was compared to maternal uniparental disomy 14.

Trisomy 20q. A new case and further phenotypic delineation.

Abstract: The present report concerns the clinical and cytogenetic findings in a liveborn girl with trisomy for the long arm of chromosome 20. She was the unbalanced product of a maternal t(18;20)(q23.2;q13.1) translocation. Our case is compared to the 3 previous reports of trisomy 20q associated with telomeric translocation. Adenosine deaminase dosage falls in the normal range and confirms the exclusion of the ADA locus from the region extending distally to 20q13.1.

Mental retardation with blepharo-naso-facial abnormalities and hand malformations: a new syndrome?

Abstract: Van Maldergem L, Wetzburger C, Verloes A, Fourneau C, Gillerot Y. Mental retardation with blepharo-naso-facial abnormalities and hand malformations: a new syndrome. Clin Genet 1992:41: 22–24. A syndrome involving facial abnormalities (telecanthus, epicanthus, broad flattened nose, large inverted W-shaped mouth and malformed ears), malformed extremities (camptodactyly, clinodactyly, interdigital webbing and joint hyperlaxity) and mental retardation is described in a girl at birth and at 11 years old. A comparison with Pashayan-Pruzansky syndrome, fetal alcohol syndrome, VATER association, Marden-Walker syndrome and Tel-Hashomer syndrome is discussed. We suggest this patient represents a new malformation syndrome or an extreme pheno-typic variant of one of the above-mentioned syndromes.

Microcephalic osteodysplastic dwarfism (Type ll‐like) in siblings

Abstract: We report about two sibs showing a common pattern of birth defects, with a pedigree suggestive of autosomal recessive heredity. The main fcatures are intrauterine growth failure with very low birthweight; disproportionate dwarfism with predominantly distal shortening of limbs; small cubitally inclined clenched hands; microcephaly with Seckel-like facies and delayed psychomotor development. X-ray findings include metaphysal flare, V-shaped femoral meta-physes and bowing of forearms. Primordial microcephalic osteodysplastic dwarfism Type II is discussed. Metabolic and nutritional data are presented and discussed.

CEMARA: a Web dynamic application within a N-tier architecture for rare diseases.

Abstract: Rare diseases include a group of conditions characterized by a prevalence lower than 5 per 10,000 in the community In France, any rare disease affects less than 30,000 patients and often much less Three to 4% of children and 6% of the population in Europe are affected It is a true public health stake since most diseases do not have any curative treatment In France, the Ministry of Health has initiated a National Rare Diseases Plan Twenty five out of 132 labelled Reference Centres (RC) decided to share a common Information System named CEMARA It is dedicated to collect continuous and complete records of all patients presenting with a rare disease, and their follow-up The main objective of CEMARA is to contribute to the missions of the RC regarding the registration and description of their activities, coordination of the network of their correspondents, organization of the follow-up of rare diseases, and analysis of the epidemiological patterns A description of CEMARA is provided as well as its cooperation with Orphanet and Genatlas, and a presentation of 11803 current records collected by more than 300 health care professionals belonging to more than 70 sites

A new form of skeletal dysplasia with amelogenesis imperfecta and platyspondyly

Abstract: We report two patients, born of consanguineous parents, affected by a disorder resulting in mild growth retardation. Hallmarks are amelogenesis imperfecta (absence of the enamel cap) associated with brachyolmia-like anomalies: platyspondyly with short pedicles, narrow intervertebral and interpedicular distances, rectangular-shaped vertebrae with posterior scalloping and herniation of the nuclei, and broad femoral necks. Inheritance appears to be autosomal recessive.

Partial trisomy of chromosome 22 resulting from a supernumerary marker chromosome 22 in a child with features of cat eye syndrome.

Abstract: Small supernumerary marker chromosomes are present in about 005% of the human population In approximately 28% of persons with these markers (excluding the ∼60% derived from one of the acrocentric chromosomes), an abnormal phenotype is observed We report on a 3-month-old girl with intrauterine growth retardation, craniofacial features, hypotonia, partial coloboma of iris and total anomalous pulmonary venous return Cytogenetic analysis showed the presence of a supernumerary marker chromosome, identified by fluorescence in situ hybridization as part of chromosome 22, and conferring a proximal partial trisomy 22q2221, not encompassing the DiGeorge critical region (RP11–154H4 + , TBX1-) This observation adds new information relevant to cat eye syndrome and partial trisomy of 22q © 2008 Wiley-Liss, Inc

Nosology of fetal hypokinesia sequence based on CNS abnormalities: is there an Aase-Smith syndrome?

Abstract: Aase-Smith syndrome (ASS) is usually defined as a dominantly inherited combination of arthrogryposis, Dandy-Walker malformation and cleft palate. We describe a sporadic case of foetal akinesia with abnormal fossa posterior, fitting the diagnosis of ASS, and discuss the nosology of this entity among syndromes with distal arthrogryposis. ASS shows a "hybrid" phenotype: adults with mild ASS could be classified as distal arthrogryposis, whereas severely affected newborns overlap with the Marden-Walker phenotype, which is recessively inherited. The specificity of the disorder comes from the coexistence of both forms in the same pedigree, so that ASS appears impossible to diagnose with certitude in sporadic cases. We suggest that the severe expression of ASS is only the extreme but aspecific expression of a dominantly inherited form of distal arthrogryposis. Implications for genetic counselling in distal arthrogryposis are outlined.

Le syndrome de Smith-Magenis

Abstract: Le syndrome de Smith Magenis (SMS) est une maladie genetique orpheline due a une microdeletion sur le chromosome 17. Il se traduit par un retard mental, une dysmorphie, des troubles du comportement et des troubles du sommeil tres severes. Ces anomalies comportementales ont ete rattachees a une anomalie de la secretion circadienne de melatonine, avec une secretion diurne et non pas nocturne de cette hormone. Le syndrome de Smith Magenis apporte la demonstration de l’impact d’une anomalie biologique sur des troubles du sommeil dans une maladie genetique. Cette anomalie du rythme circadien est unique dans l’espece humaine et ce syndrome est donc un modele des liens etroits qui peuvent exister entre la genetique, la biologie et les troubles du comportement. La comprehension de ce desordre biologique a permis une approche therapeutique originale, par des medicaments d’utilisation simple, ce qui a transforme le sommeil des patients et ameliore leur comportement diurne.