ABSTRACT
We demonstrate theoretically and experimentally a high level of control of the four-wave mixing process in an inert gas-filled inhibited-coupling guiding hollow-core photonic crystal fiber. The specific multiple-branch dispersion profile in such fibers allows both correlated and separable bi-photon states to be produced. By controlling the choice of gas and its pressure and the fiber length, we experimentally generate various joint spectral intensity profiles in a stimulated regime that is transferable to the spontaneous regime. The generated profiles may cover both spectrally separable and correlated bi-photon states and feature frequency tuning over tens of THz, demonstrating a large dynamic control that will be very useful when implemented in the spontaneous regime as a photon pair source.
ABSTRACT
TTC7A mutations cause multiple neonatal intestinal atresias with early inflammatory bowel disease and severe combined immunodeficiency. There are no treatment protocols for this rare disease. Two new cases are described for which radical early treatment measures - total enterectomy, home parenteral nutrition, immunoglobulin therapy and intravenous antibiotic prophylaxis - have allowed both patients to develop optimally.
ABSTRACT
Wiedemann-Steiner syndrome (WSS) is a rare syndromic condition in which intellectual disability (ID) is associated with hypertrichosis cubiti, short stature, and characteristic facies. Following the identification of the causative gene (KMT2A) in 2012, only 31 cases of WSS have been described precisely in the literature. We report on 33 French individuals with a KMT2A mutation confirmed by targeted gene sequencing, high-throughput sequencing or exome sequencing. Patients' molecular and clinical features were recorded and compared with the literature data. On the molecular level, we found 29 novel mutations. We observed autosomal dominant transmission of WSS in 3 families and mosaicism in one family. Clinically, we observed a broad phenotypic spectrum with regard to ID (mild to severe), the facies (typical or not of WSS) and associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Hypertrichosis cubiti that was supposed to be pathognomonic in the literature was found only in 61% of our cases. This is the largest series of WSS cases yet described to date. A majority of patients exhibited suggestive features, but others were less characteristic, only identified by molecular diagnosis. The prevalence of WSS was higher than expected in patients with ID, suggesting than KMT2A is a major gene in ID.
Subject(s)
Intellectual Disability/diagnosis , Intellectual Disability/etiology , Adolescent , Amino Acid Substitution , Child , Child, Preschool , Disease Susceptibility , Female , France , High-Throughput Nucleotide Sequencing , Histone-Lysine N-Methyltransferase/genetics , Humans , Magnetic Resonance Imaging , Male , Mutation , Myeloid-Lymphoid Leukemia Protein/genetics , Phenotype , Syndrome , Tomography, X-Ray ComputedABSTRACT
We report on the experimental characterization of a novel nonlinear liquid-filled hollow-core photonic crystal fiber for the generation of photon pairs at a telecommunication wavelength through spontaneous four-wave mixing (SFWM). We show that the optimization procedure in view of this application links the choice of the nonlinear liquid to the design parameters of the fiber, and we give an example of such an optimization at telecom wavelengths. Combining the modeling of the fiber and classical characterization techniques at these wavelengths, we identify for the chosen fiber and liquid combination SFWM phase-matching frequency ranges with no Raman scattering noise contamination. This is a first step toward obtaining a telecom band fibered photon-pair source with a high signal-to-noise ratio.
ABSTRACT
OBJECTIVES: This study aims to describe how microarray comparative genomic hybridization (aCGH) has shifted to become a prenatal diagnosis tool at the Lyon university-hospital. MATERIALS AND METHODS: This retrospective study included all patients who were referred in the 3 pluridisciplinary centers for prenatal diagnosis of the Lyon university-hospital and who received a prenatal aCGH between June 2013 and June 2015. aCGH was systematically performed in parallel with a karyotype, using the PréCytoNEM array design. RESULTS: A total of 260 microarrays were performed for the following indications: 249 abnormal ultrasounds (95.8%), 7 characterizations of chromosomal rearrangements (2.7%), and 4 twins with no abnormal ultrasounds (1.5%). With a resolution of 1 mega base, we found 235 normal results (90.4%), 23 abnormal results (8.8%) and 2 non-returns (0.8%). For the chromosomal rearrangements visible on the karyotype, aCGH identified all of the 12 unbalanced rearrangements and did not identify the 2 balanced rearrangements. Among the fetuses with normal karyotypes, 11 showed abnormal microarray results, corresponding to unbalanced cryptic chromosomal rearrangements (4.2%). CONCLUSION: Transferring aCGH to a prenatal diagnosis at the Lyon university-hospital has increased the detection rate of chromosomal abnormalities by 4.2% compared to the single karyotype.
Subject(s)
Chromosome Aberrations , Chromosome Disorders/diagnosis , Comparative Genomic Hybridization , Prenatal Diagnosis , Adolescent , Adult , Female , France , Hospitals, University , Humans , Pregnancy , Retrospective Studies , Young AdultABSTRACT
Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.
Subject(s)
Comparative Genomic Hybridization/methods , Genetic Counseling/ethics , Genetic Counseling/methods , Incidental Findings , Disclosure/ethics , Female , France , Genes, Dominant/genetics , Genes, Recessive/genetics , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Diseases, X-Linked/diagnosis , Genetic Diseases, X-Linked/genetics , Humans , Male , Microarray Analysis/methods , Physician-Patient Relations/ethics , Retrospective Studies , Surveys and QuestionnairesABSTRACT
Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.
Subject(s)
Craniofacial Abnormalities/genetics , Fetus , Filamins/genetics , Hand Deformities, Congenital/genetics , Mutation , Osteochondrodysplasias/genetics , Phenotype , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/metabolism , DNA Mutational Analysis , Female , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/metabolism , Humans , Infant, Newborn , Male , Osteochondrodysplasias/diagnosis , Osteochondrodysplasias/metabolism , PedigreeABSTRACT
Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the numbers of known genes remain low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type poikiloderma with neutropenia, hereditary sclerosing poikiloderma, and craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with poikiloderma, as well as BGS without poikiloderma.
Subject(s)
Craniosynostoses/diagnosis , Craniosynostoses/genetics , Genotype , Radius/abnormalities , RecQ Helicases/genetics , Adolescent , Adult , Child , Child, Preschool , Comparative Genomic Hybridization , Consanguinity , Facies , Female , Humans , Infant , Male , Mutation , Phenotype , Young AdultABSTRACT
Array comparative genomic hybridization (aCGH) has progressively replaced conventional karyotype in the diagnostic strategy of intellectual disability (ID) and congenital malformations. This technique increases not only the diagnostic rate but also the possibility of finding unexpected variants unrelated to the indication of referral, namely incidental findings. The incidental finding of copy number variants (CNVs) located in X-linked genes in girls addresses the crucial question of genetic counseling in the family. We report here five cases of CNVs involving the dystrophin gene detected by aCGH in girls referred for developmental delay, without any family history of dystrophinopathy. The rearrangements included three in-frame deletions; one maternally and two paternally inherited, and two frameshift duplications: one de novo and one from undetermined inheritance. In two cases, the deletion identified in a girl was transmitted by the asymptomatic father. In the case of the maternally inherited deletion, prenatal diagnosis of dystrophinopathy was proposed for an ongoing pregnancy, whereas the cause of developmental delay in the index case remained unknown. Through these cases, we discussed the challenges of genetic counseling in the family, regarding the predictive issues for male individuals at risk for a muscular dystrophy without precise knowledge of the clinical consequences of some CNVs in the DMD gene.
Subject(s)
Comparative Genomic Hybridization , Heterozygote , Incidental Findings , Child, Preschool , DNA Copy Number Variations , Dystrophin/genetics , Family , Female , Genetic Counseling , Humans , Infant , Muscular Dystrophies/diagnosis , Muscular Dystrophies/geneticsABSTRACT
BACKGROUND: The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. METHODS: We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. RESULTS: Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. CONCLUSIONS: Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be a safer and more effective treatment to prevent early recurrence. However, intravenous thrombolysis should not be withheld in eligible stroke patients.
Subject(s)
Brain Ischemia/drug therapy , Fibrinolytic Agents/adverse effects , Thrombosis/drug therapy , Tissue Plasminogen Activator/adverse effects , Administration, Intravenous , Aged , Aged, 80 and over , Cerebral Angiography/methods , Female , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Stroke , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/therapeutic use , Treatment OutcomeABSTRACT
Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.
Subject(s)
Chromosome Aberrations , Genetic Counseling , Genetic Predisposition to Disease , Prognosis , Adult , Comparative Genomic Hybridization , Female , France , Genetic Association Studies , Genetic Markers , Genome-Wide Association Study , Humans , In Situ Hybridization, Fluorescence , Karyotype , Middle Aged , Polymorphism, Single Nucleotide , Pregnancy , Prenatal Diagnosis , Prospective Studies , Risk , Switzerland , Young AdultABSTRACT
PURPOSE: To highlight meningoencephalitis as a transient ischaemic attack (TIA) mimic and suggest clinical clues for differential diagnosis. METHODS: This was an observational study of consecutively admitted patients over a 9.75-year period presenting as TIAs at a stroke unit. RESULTS: A total of 790 patients with TIAs and seven with TIA-like symptoms but a final diagnosis of viral meningoencephalitis were recognised. The most frequent presentations of meningoencephalitis patients were acute sensory hemisyndrome (6) and cognitive deficits (5). Signs of meningeal irritation were minor or absent on presentation. Predominantly lymphocytic pleocytosis, hyperproteinorachia and a normal cerebrospinal fluid (CSF)/serum glucose index (in 5 out of 6 documented patients) were present. Meningeal thickening on a brain magnetic resonance imaging (MRI) scan was the only abnormal imaging finding. Six patients received initial vascular treatment; one thrombolysed. Finally, six patients were treated with antivirals and/or antibiotics. Although neither bacterial nor viral agents were identified on extensive testing, viral meningoencephalitis was the best explanation for all clinical and laboratory findings. CONCLUSIONS: Aseptic meningoencephalitis should be part of the differential diagnosis in patients presenting as TIA. The threshold for a lumbar puncture in such patients should be set individually and take into account the presence of mild meningeal symptoms, age and other risk factors for vascular disease, the results of brain imaging and the basic diagnostic work-up for a stroke source.
Subject(s)
Ischemic Attack, Transient/diagnosis , Meningoencephalitis/diagnosis , Stroke/pathology , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Antiviral Agents/administration & dosage , Brain/diagnostic imaging , Cognition Disorders/pathology , Diagnosis, Differential , Female , Humans , Ischemic Attack, Transient/drug therapy , Male , Meningoencephalitis/drug therapy , Middle Aged , Radiography , Simplexvirus , Treatment Outcome , Young AdultABSTRACT
Among possible mitigation options to reduce agricultural-borne nitrate fluxes to water bodies, introduction of catch crop before spring crops is acknowledged as a cost-efficient solution at the plot scale, but it was rarely assessed at the catchment level. This study aims to evaluate a set of catch crop implantation scenarios and their consequences in a coastal catchment prone to eutrophication. The objectives are (i) to discuss the potential benefits of catch crop introduction taking into account the limitations due to the physiographic and agricultural context of the area (ii) to propose a multicriteria classification of these scenarios as a basis for discussion with stakeholders. We used the distributed agro-hydrological model TNT2 to simulate 25 scenarios of catch crop management, differing in length of catch crop growing period, place in the crop rotation and residue management. The scenarios were classified considering the variations in main crop yields and either nitrogen fluxes in stream or the global nitrogen mass balance at the catchment level. The simulations showed that in the catchment studied, little improvement can be expected from increasing the catch crop surface. Catch crop cultivation was always beneficial to reduce nitrogen losses, but led to adverse effects on main crop yields in some cases. Among the scenarios involving additional catch crop surface, introducing catch crop between two winter cereals appeared as the most promising. The classification of scenarios depended on the chosen criteria: when considering only the reduction of nitrogen fluxes in streams, exporting catch crop residues was the most efficient while when considering the global nitrogen mass balance, soil incorporation of catch crop residues was the most beneficial. This work highlights the interest, while using integrated models, of assessing simulated scenarios with multicriteria approach to provide stakeholder with a picture as complete as possible of the consequences of prospective policies.
Subject(s)
Agriculture , Crops, Agricultural , Water Pollutants, Chemical/analysis , Computer Simulation , Edible Grain , Europe , Humans , Models, Biological , Nitrogen Cycle , Rivers/chemistryABSTRACT
The increasing use of array-comparative genomic hybridization (array-CGH) to identify copy number variations (CNVs) in patients with developmental delay (DD), mental retardation and/or dysmorphic features has allowed the recent recognition of numerous genomic imbalances, including the 15q13.3 microdeletion. Patients with this microdeletion generally present with relatively consistent breakpoints at BP4 and BP5, which include the CHRNA7 gene. About 100 index cases have been reported since the first publication in 2008. This large number of patients ascertained through highly variable samples has been necessary to describe the full phenotypic spectrum of this microdeletion, ranging from mental retardation with dysmorphic features, epilepsy, neuropsychiatric disturbances with or without cognitive impairment to complete absence of anomalies. Here, we describe a collaborative study reporting a new cohort of 12 index patients and 13 relatives carrying a heterozygous BP4-BP5 microdeletion out of a series of 4625 patients screened by array-CGH for DD. We confirm the clinical expressivity of the disease as well as the incomplete penetrance in seven families. We showed through a review of the literature that males are more likely to be symptomatic. Sequence analysis of CHRNA7 yielded no data to support the unmasking of recessive variants as a cause of phenotypic variability. We also report the first patient carrying a 15q13.3 homozygous microdeletion inherited from both parents. He had severe epileptic encephalopathy with retinopathy, autistic features and choreoathetosis. Besides the classical approximately 1.5 Mb BP4-BP5 microdeletion, we also describe three index patients and two relatives with a smaller 500 kb microdeletion, including the CHRNA7 gene.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 15/genetics , Adolescent , Base Pairing/genetics , Child , Child, Preschool , Comparative Genomic Hybridization , Female , Heterozygote , Humans , Inheritance Patterns/genetics , Male , Pedigree , PhenotypeABSTRACT
Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 16/genetics , Obesity/genetics , Obesity/physiopathology , Penetrance , Adolescent , Adult , Age of Onset , Aging , Body Mass Index , Case-Control Studies , Child , Cognition Disorders/complications , Cognition Disorders/genetics , Cohort Studies , Europe , Female , Genome-Wide Association Study , Heterozygote , Humans , Inheritance Patterns/genetics , Male , Mutation/genetics , Obesity/complications , Reproducibility of Results , Sex Characteristics , Young AdultSubject(s)
Corneal Diseases/genetics , Corneal Diseases/pathology , Lens, Crystalline/pathology , Mutation , Optic Nerve/abnormalities , PAX2 Transcription Factor/genetics , Child , Coloboma/genetics , Coloboma/physiopathology , Female , Humans , Phenotype , Renal Insufficiency/genetics , Renal Insufficiency/physiopathology , Vesico-Ureteral Reflux/genetics , Vesico-Ureteral Reflux/physiopathologyABSTRACT
Wiedemann-Beckwith syndrome (WBS) is a syndrome of excessive growing with a high predisposition to developing embryologic tumours within the first years of life. This risk is evaluated between 7.5 and 10%; it varies with the mechanisms of mutations involved. These take place in two distinct domains of 11p15, which are under parental printing. Emerging techniques of cytogenetic and molecular biology now have shown correlations between genotypes and phenotypes, and can identify the 30% of WBS who are especially at risk of developing tumours. A specific follow-up, integrating the specificity of developing tumours of each 11p15 mutations involved, is now proposed to patients with WBS.
Subject(s)
Beckwith-Wiedemann Syndrome/genetics , Genetic Predisposition to Disease , Neoplasms/genetics , Genotype , Humans , Infant , Phenotype , RiskABSTRACT
Two patients, with prior affected children with Neonatal Haemochromatosis [NH], benefited from intravenous immunoglobulin treatment during their following pregnancy in order to prevent recurrent NH. Whereas NH is a severe disease with high risk of recurrence and high mortality rate (about 80%), a recent treatment was suggested in the USA, which seems to completely modify the prognosis of this pathology. We proposed this treatment for two patients with indeed apparent benefit, giving birth to two healthy babies.
Subject(s)
Hemochromatosis/prevention & control , Immunoglobulins/administration & dosage , Adult , Female , Humans , Infant, Newborn , Pregnancy , Prognosis , RecurrenceSubject(s)
Genetic Testing , Kidney Diseases/genetics , Magnetic Resonance Imaging , Prenatal Diagnosis , Ultrasonography, Prenatal , Balkan Nephropathy/diagnosis , Balkan Nephropathy/genetics , Consanguinity , Cystinosis/diagnosis , Cystinosis/genetics , Female , Humans , Hyperoxaluria, Primary/diagnosis , Hyperoxaluria, Primary/genetics , Infant, Newborn , Kidney Diseases/diagnosis , Nephritis, Hereditary/diagnosis , Nephritis, Hereditary/genetics , Phenotype , Polycystic Kidney, Autosomal Recessive/diagnosis , Polycystic Kidney, Autosomal Recessive/genetics , Pregnancy , PrognosisABSTRACT
We report the cases of 2 boys and 1 girl suffering from Netherton syndrome. Both boys presented with a non-bullous congenital erythroderma and were diagnosed early as Netherton syndrome with hair biopsies. Both had severe failure to thrive, signs of atopy, several episodes of bacterial infection, and rickets (with a high blood level of vitamin D in the first boy, and vitamin D deficiency in the second). In the third case, the pilar abnormality appeared at the age of 3 years. The girl had ichtyosis linearis circumflexa, failure to thrive and severe constipation. Netherton syndrome is a rare disorder characterized by severe ichtyosis, signs of atopy, immune deficiency and failure to thrive. The disease is severe and comprises many complications in early infancy. It is due to a genetic disorder of recessive autosomal transmission, and the gene, SPINK5, is located in the chromosome 5. Prenatal diagnosis is possible. Two of our patients had rickets, which has never been described in such patients population.