Isaac Sutton
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PROVIDER: S-EPMC1122165 | biostudies-literature | 2002 Jan
REPOSITORIES: biostudies-literature
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Project description:One of the pioneers of liaison psychiatry
| S-EPMC543885 | biostudies-literature
Project description: Not available
| S-EPMC556116 | biostudies-literature
Project description:White-Sutton syndrome (WHSUS) is a recently-identified genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ. Thus far, over 50 individuals have been reported worldwide, however phenotypic characterization and data regarding the natural history are still incomplete. Here we report the clinical features of 22 individuals with 21 unique loss of function POGZ variants. We observed a broad spectrum of intellectual disability and/or developmental delay with or without autism, and speech delay in all individuals. Other common problems included ocular abnormalities, hearing loss and gait abnormalities. A validated sleep disordered breathing questionnaire identified symptoms of obstructive sleep apnea in 4/12 (33%) individuals. A higher-than-expected proportion of cases also had gastrointestinal phenotypes, both functional and anatomical, as well as genitourinary anomalies. In line with previous publications, we observed an increased body mass index (BMI) z-score compared to the general population (mean 0.59, median 0.9; p 0.0253). Common facial features included microcephaly, broad forehead, midface hypoplasia, triangular mouth, broad nasal root and flat nasal bridge. Analysis of the Baylor Genetics clinical laboratory database revealed that POGZ variants were implicated in approximately 0.14% of cases who underwent clinical exome sequencing for neurological indications with or without involvement of other body systems. This study describes a greater allelic series and expands the phenotypic spectrum of this new syndromic form of intellectual disability and autism.
| S-EPMC7713511 | biostudies-literature
Project description:Isaac syndrome (IS) is a peripheral nerve hyperexcitability state associated with voltage-gated potassium channel (VGKC) complex antibodies. Major manifestations are muscle twitching, stiffness, hypertrophy, and dysautonomic features such as hyperhidrosis [Ahmed and Simmons. Muscle Nerve. 2015;52(1):5-12]. Neuropathic pain is a rare manifestation. We describe a case of IS characterized by muscle twitching and intractable neuropathic pain. Diagnostic workup included elevated VGKC complex antibodies and EMG/NC that showed neuromyotonic discharges. Neuropathic pain was initially difficult to relieve even after using multiple medications, including opiates, benzodiazepines, anticonvulsants, and intravenous immunoglobulin (IVIg). Moderate pain control was eventually achieved with long-term use of carbamazepine and subcutaneous immunoglobulin (SCIg). Common manifestations of IS are muscle twitching, stiffness hypertrophy, and dysautonomia [Ahmed and Simmons. Muscle Nerve. 2015;52(1):5-12]. Sensory manifestations such as neuropathic pain are rare, but, as illustrated by our patient, can be the most distressing symptom. In our patient, not only was neuropathic pain disabling but it also showed the least response to IVIg. The use of 200 mg of long-acting carbamazepine twice daily with weekly SCIg demonstrated the best response. This case highlights an uncommon but potentially resistant symptom of IS.
| S-EPMC9035955 | biostudies-literature
Project description:BackgroundWhite-Sutton syndrome is an autosomal dominant neurodevelopmental disorder caused by heterozygous mutation in POGZ (Pogo Transposable Element Derived with ZNF Domain). This syndrome is characterized by delayed psychomotor development apparent in infancy and abnormal facial features. To date, 80 cases have been reported in the literature; however, the phenotypic characterizations remain incomplete.Case presentationWe herein describe a 2-year-old girl harboring a novel frameshift de novo POGZ variant: c.2746del (p.Thr916ProfsTer12). This patient presented with multisystem abnormalities affecting the digestive tract and neurological functioning, as well as congenital heart disease, which involved an atrial septal defect (18 × 23 × 22 mm) with pulmonary arterial hypertension (42 mmHg). The relationship between congenital heart disease and White-Sutton syndrome as described in both the GeneReview and OMIM databases (#616,364) remains unclear. A review of the current literature revealed 18 cases of White-Sutton syndrome with POGZ variants and congenital heart disease, and we summarize their clinical features in this study.ConclusionsOur findings based on the present case and those in the literature indicate a relationship between POGZ mutation and congenital heart disease.
| S-EPMC10071667 | biostudies-literature
Project description:White-Sutton syndrome (WHSUS), which is caused by heterozygous pathogenic variants in POGZ, is characterized by a spectrum of intellectual disabilities and global developmental delay with or without features of autism spectrum disorder. Additional features may include hypotonia, behavioral abnormalities, ophthalmic abnormalities, hearing loss, sleep apnea, microcephaly, dysmorphic facial features, and rarely, congenital diaphragmatic hernia (CDH). We present a 6-year-old female with features of WHSUS, including CDH, but with nondiagnostic clinical trio exome sequencing. Exome sequencing reanalysis revealed a heterozygous, de novo, intronic variant in POGZ (NM_015100.3:c.2546-20T>A). RNA sequencing revealed that this intronic variant leads to skipping of exon 18. This exon skipping event results in a frameshift with a predicted premature stop codon in the last exon and escape from nonsense-mediated mRNA decay (NMD). To our knowledge, this case is the first case of WHSUS caused by a de novo, intronic variant that is not near a canonical splice site within POGZ. These findings emphasize the limitations of standard clinical exome filtering algorithms and the importance of research reanalysis of exome data together with RNA sequencing to confirm a suspected diagnosis of WHSUS. As the sixth reported case of CDH with heterozygous pathogenic variants in POGZ and features consistent with WHSUS, this report supports the conclusion that WHSUS should be considered in the differential diagnosis for patients with syndromic CDH.
| S-EPMC9197987 | biostudies-literature
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:POGZ is located on chromosome 1q21.3, encoding a pogo transposable element-derived protein with a zinc finger cluster. White-Sutton syndrome (WHSUS, OMIM:616364) is a genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ, which manifests as intellectual disability, autism spectrum disorder, specific facial features and other phenotypic spectra. To date, a total of twenty-one de novo POGZ mutations in WHSUS have been reported. Here we report the identification of a novel missense variant in the coding region of the POGZ gene (c.4042G>C), which occurred in a 15-year-old male and his mother with WHSUS. We describe their clinical features and compare them with clinical data of patients with WHSUS from the literature. Our finding broadens the spectrum of POGZ mutations and provides a good example of precision medicine through the combination of exome sequencing and clinical testing.
| S-EPMC8265545 | biostudies-literature
Project description:To study the prevalence and interrelationship between asthma, allergic rhinitis and eczema using data obtained from ISAAC questionnaires.The Medline, Pubmed Publisher, EMBASE, Google Scholar and the Cochrane Controlled Clinical Trials Register databases were systematically reviewed to evaluate epidemiological data of children with atopic disorders. To study these interrelationships, a new approach was used. Risk ratios were calculated, describing the risk of having two different atopic disorders when the child is known with one disorder.Included were 31 studies, covering a large number of surveyed children (n=1,430,329) in 102 countries. The calculated worldwide prevalence for asthma, eczema and allergic rhinitis is 12.00% (95% CI: 11.99-12.00), 7.88% (95% CI: 7.88-7.89) and 12.66% (95% CI: 12.65-12.67), respectively. The observed prevalence [1.17% (95% CI: 1.17-1.17)] of having all three diseases is 9.8 times higher than could be expected by chance. For children with asthma the calculated risk ratio of having the other two disorders is 5.41 (95% CI: 4.76-6.16), for children with eczema 4.24 (95% CI: 3.75-4.79), and for children with allergic rhinitis 6.20 (95% CI: 5.30-7.27). No studied confounders had a significant influence on these risk ratios.Only a minority of children suffers from all three atopic disorders, however this co-occurrence is significantly higher than could be expected by chance and supports a close relationship of these disorders in children. The data of this meta-analysis supports the hypothesis that there could be a fourth distinct group of children with all three disorders. Researchers and clinicians might need to consider these children as a separate group with distinct characteristics regarding severity, causes, treatment or prognosis.
| S-EPMC4489894 | biostudies-literature