A case of neonatal Jeune syndrome expanding the phenotype.
Ontology highlight
ABSTRACT:
SUBMITTER: Drera B
PROVIDER: S-EPMC4184654 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
Publications
A case of neonatal Jeune syndrome expanding the phenotype.
Drera Bruno B Ferrari Daniela D Cavalli Pietro P Poggiani Carlo C
Clinical case reports 20140602 4
<h4>Key clinical message</h4>We report the case of a premature, very low birth weight, newborn with stigmata of Jeune syndrome, a rare skeletal dysplasia, and marked renal involvement (i.e. remarkable prenatal oligohydramnios, histologic nephronophthisis-like pattern, macroscopic renal cysts, and renal failure), expanding the phenotype consistent with the continuum of syndromic ciliopathies. ...[more]
Similar Datasets
Project description:BackgroundWhite-Sutton (WHSUS) is a recently recognized syndrome caused by mutations of the POGZ gene. Approximately 70 patients have been reported to date. Intellectual disability, hypotonia, behavioral abnormalities, autism, and typical facial dysmorphisms are recognized as WHSUS features; however, still few patients receive a comprehensive psychometric, behavioral and neurological examination. In this report, we describe the pediatric, dysmorphological, neurological, psychometric and behavioral phenotype in a new WHSUS patient due to a novel heterozygous POGZ mutation, highlighting the distinctive epileptic phenotype and the cognitive pattern.Case presentationThe patient, an 8 years-old girl, presented history of hypotonia, motor and speech delay, and distinctive facial features. The diagnosis of WHSUS followed the identification of the de novo variant p.Asp828GlyfsTer36 (c.2482dupG) in the POGZ gene. The patient showed a distinctive neurological phenotype with the occurrence of both paroxysmal not-epileptic events in the first 6 months of age and EEG abnormalities without evidence of clinical seizures after the first year of age. Psychological and behavioral testing highlighted moderate intellectual and communication deficit, mild autism spectrum and visual-motor integration deficit.ConclusionsThis is the first described case of WHSUS with a co-existence of paroxysmal not-epileptic events and abnormal EEG without seizures in the same patient. Together with the available literature data, this observation suggests that paroxysmal not-epileptic events could be more frequent than expected and that this feature belongs to the WHSUS phenotypic spectrum. Autism is a known comorbidity of WHSUS but is still poorly investigated. Specific clinical testing could help detect also mild autistic phenotypes and better define autism prevalence in POGZ-related syndrome. Special attention should be given to symptoms such as stereotypies, social withdrawal, and hyperactivity that, when present, should be considered as possible signs of autism symptoms. The dissection of the neurological and behavioral phenotype is crucial for individualized therapies tailored to patient's needs.
| S-EPMC8254207 | biostudies-literature
Project description:ALG11-Congenital Disorder of Glycosylation (ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11-CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesized truncated precursor glycan structures, consistent with ALG11-CDG, while also showing hypoglycosylation of a novel biomarker, GP130. Surprisingly, one patient presented with normal transferrin glycosylation profile, a feature that has not been reported previously in patients with ALG11-CDG. Together, our data expand the clinical and mutational spectrum of ALG11-CDG.
| S-EPMC6426632 | biostudies-literature
Project description:PURA syndrome is a recently described developmental encephalopathy presenting with neonatal hypotonia, feeding difficulties, global developmental delay, severe intellectual disability, and frequent apnea and epilepsy. We describe 18 new individuals with heterozygous sequence variations in PURA. A neuromotor disorder starting with neonatal hyptonia, but ultimately allowing delayed progression to walking, was present in nearly all individuals. Congenital apnea was present in 56% during infancy, but all cases in this cohort resolved during the first year of life. Feeding difficulties were frequently reported, with gastrostomy tube placement required in 28%. Epilepsy was present in 50% of the subjects, including infantile spasms and Lennox-Gastaut syndrome. Skeletal complications were found in 39%. Disorders of gastrointestinal motility and nystagmus were also recurrent features. Autism was diagnosed in one individual, potentially expanding the neurodevelopmental phenotype associated with this syndrome. However, we did not find additional PURA sequence variations in a cohort of 120 subjects with autism. We also present the first neuropathologic studies of PURA syndrome, and describe chronic inflammatory changes around the arterioles within the deep white matter. We did not find significant correlations between mutational class and severity, nor between location of the sequence variation in PUR repeat domains. Further studies are required in larger cohorts of subjects with PURA syndrome to clarify these genotype-phenotype associations.
| S-EPMC5821266 | biostudies-literature
Project description:BACKGROUND: The differential diagnosis of a neonate or fetus presenting with a bell-shaped or long narrow thorax includes a wide range of bony dysplasia syndromes. Where this is accompanied by respiratory distress, asphyxiating thoracic dystrophy (ATD, Jeune syndrome) is an important potential diagnosis. Shwachman-Diamond syndrome (SDS) is widely recognised as a cause of exocrine pancreatic dysfunction, short stature and bone marrow failure. It is not so well appreciated that rib and/or thoracic cage abnormalities occur in 30-50% of patients and that, in severe cases, these abnormalities may lead to thoracic dystrophy and respiratory failure in the newborn. There are, however, at least three previous case reports of children who were initially diagnosed with ATD who were subsequently shown to have SDS. CASE PRESENTATION: This report details the case history of a patient misdiagnosed as having ATD as a neonate following the neonatal asphyxial death of her brother. She subsequently developed progressive pancytopenia but was only diagnosed with SDS at 11 years of age after referral for haematopoietic stem cell transplantation for bone marrow failure accompanied by trilineage dysplasia and clonal cytogenetic abnormalities on bone marrow examination. Subsequent testing revealed the presence of fat globules in stools, reduced faecal chymotrypsin, fat-soluble vitamin deficiency, metaphyseal dysplasia on skeletal survey and heterozygous mutations of the SBDS gene. CONCLUSION: This report highlights the potential for diagnostic confusion between ATD and SDS. It is important to include SDS in the differential diagnosis of newborns with thoracic dystrophy and to seek expert clinical and radiological assessment of such children.
| S-EPMC3457858 | biostudies-literature
Project description:Chromosomal abnormalities on the short arm of chromosome 2 in the region p11.2 have been associated with developmental delay, intellectual disability, facial anomalies, abnormal ears, skeletal and genital malformations. Here we describe a patient with a de novo interstitial heterozygous microdeletion on the short arm of chromosome 2 in the region p11.2-p12. He presents with facial dysmorphism characterized by a broad and low root of the nose and low-set protruding ears. Clinical examinations during follow-up visits revealed congenital pendular nystagmus, decreased visual acuity and psychomotor development disorder including intellectual disability. The heterozygous 5 Mb-microdeletion was characterized by an array CGH (Comparative Genomic Hybridization) analysis. In the past two decades, nine patients with microdeletions in this region have been identified by array CGH analysis and were reported in the literature. All these patients show psychomotor development disorder and outer and/or inner ear anomalies. In addition, most of the patients have mild to severe intellectual disability and show facial malformations. We reviewed the literature on PubMed and OMIM using the gene/loci names as search terms in an attempt to identify correlations between genes located within the heterozygous microdeletion and the clinical phenotype of the patient, in order to define a recognizable phenotype for the 2p11.2p12 microdeletion syndrome. We discuss additional symptoms that are not systematically present in all patients and contribute to a heterogeneous clinical presentation of this microdeletion syndrome.
| S-EPMC10742694 | biostudies-literature
Project description:Ring chromosome 10 [r(10)] syndrome is a rare genetic condition, currently described in the medical literature in a small number of case report studies. Typical clinical features include microcephaly, short stature, facial dysmorphisms, ophthalmologic abnormalities and genitourinary malformations. We report a novel case of r(10) syndrome and review the neurological and neuroradiological phenotypes of the previously described cases. Our patient, a 3 year old Italian girl, represents the 20th case of r(10) syndrome described to date. Intellectual disability/developmental delay (ID/DD), microcephaly, strabismus, hypotonia, stereotyped/aggressive behaviors and electroencephalographic abnormalities were identified in our patient, and in a series of previous cases. A brain MRI disclosed a complex malformation involving both the vermis and cerebellar hemispheres; in the literature, posterior cranial fossa abnormalities were documented by CT scan in another case. Two genes deleted in our case (ZMYND11 in 10p and EBF3 in 10q) are involved in autosomal dominant neurodevelopmental disorders, characterized by different expressions of brain and posterior cranial fossa abnormalities, ID/DD, hypotonia and behavioral problems. Our case expands the neurological and neuroradiological phenotype of r(10) syndrome. Although r(10) syndrome represents an extremely rare condition, with a clinical characterization limited to case reports, the recurrence of specific neurological and neuroradiological features suggests the need for specific genotype-phenotype studies.
| S-EPMC8535287 | biostudies-literature
Project description:Recurrent reciprocal 1q21.1 deletions and duplications have been associated with variable phenotypes. Phenotypic features described in association with 1q21.1 microdeletions include developmental delay, craniofacial dysmorphism and congenital anomalies. The 1q21.1 reciprocal duplication has been associated with macrocephaly or relative macrocephaly, frontal bossing, hypertelorism, developmental delay, intellectual disability and autism spectrum disorder.Our study describes seven patients, who were referred to us for developmental delay/intellectual disability, dysmorphic features and, in some cases, congenital anomalies, in whom we identified 1q21.1 CNVs by array-CGH.Our data confirm the extreme phenotypic variability associated with 1q21.1 microdeletion and microduplication. We observed common phenotypic features, described in previous studies, but we also described, for the first time, congenital hypothyroidism in association with 1q21.1 deletion and trigonocephaly associated with 1q21.1 duplication.The aim of this study is to contribute to the definition of the phenotype associated with reciprocal 1q21.1 deletions and duplications.
| S-EPMC5518118 | biostudies-other
Project description:Neurologic disorders caused by mutations in the ATP1A3 gene were originally reported as three distinct rare clinical syndromes: Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and Cerebellar ataxia, Areflexia, Pes cavus, Opticus atrophy and Sensorineural hearing loss (CAPOS). In this case series, we describe 3 patients. A mother and her daughter showed an intermediate phenotype different from each other with the same heterozygous missense mutation (p.[R756C]), recently described in literature as Relapsing Encephalopathy With Cerebellar Ataxia (RECA). In addition, a third patient showed an intermediate AHC-RDP phenotype and had a likely pathogenic novel de novo missense mutation (p.[L100 V]). These patients support the growing evidence that AHC, RDP and RECA are part of a continuous ATP1A3 mutation spectrum that is still expanding. Three common features were a sudden onset, asymmetrical neurological symptoms, as well as the presence of triggering factors. When present, the authors argue to perform exome sequencing in an early stage.
| S-EPMC8573619 | biostudies-literature
Project description:Glutaminase (GLS) hyperactivity was first described in 2019 in a patient with profound developmental delay and infantile cataract. Here, we describe a 4-year-old boy with GLS hyperactivity due to a de novo heterozygous missense variant in GLS, detected by trio whole exome sequencing. This boy also exhibits developmental delay without dysmorphic features, but does not have cataract. Additionally, he suffers from epilepsy with tonic clonic seizures. In line with the findings in the previously described patient with GLS hyperactivity, in vivo 3 T magnetic resonance spectroscopy (MRS) of the brain revealed an increased glutamate/glutamine ratio. This increased ratio was also found in urine with UPLC-MS/MS, however, inconsistently. This case indicates that the phenotypic spectrum evoked by GLS hyperactivity may include epilepsy. Clarifying this phenotypic spectrum is of importance for the prognosis and identification of these patients. The combination of phenotyping, genetic testing, and metabolic diagnostics with brain MRS and in urine is essential to identify new patients with GLS hyperactivity and to further extend the phenotypic spectrum of this disease.
| S-EPMC10159865 | biostudies-literature
Project description:BackgroundInherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5. Examination of these patients included funduscopic evaluation, spectral-domain optical coherence tomography, short-wavelength autofluorescence, and full-field electroretinography (ffERG). Genetic diagnoses were confirmed using whole exome capture. Protein modeling of the identified variants was performed to explore potential genotype-phenotype correlations.ResultsGenetic testing revealed five novel variants in TTLL5 in three unrelated patients with retinal dystrophy. Clinical imaging demonstrated features of sectoral cone-rod dystrophy and cone dystrophy, with phenotypic variability seen across all three patients. One patient also developed high-frequency hearing loss during a similar time period as the onset of retinal disease, potentially suggestive of a syndromic disorder. Retinal structure findings were corroborated with functional measures including ffERG findings that supported these diagnoses. Modeling of the five variants suggest that they cause different effects on protein function, providing a potential reason for genotype-phenotype correlation in these patients.ConclusionsThe authors report retinal phenotypic findings in three unrelated patients with novel mutations causing autosomal recessive TTLL5-mediated retinal dystrophy. These findings broaden the understanding of the phenotypes associated with TTLL5-mediated retinal disease and suggest that mutations in TTLL5 should be considered as a potential cause of sectoral retinal dystrophy in addition to cone-rod and cone dystrophies.
| S-EPMC8973795 | biostudies-literature