Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association

Tufano, Maria Antonietta; Corte, Claudia Della; Cirillo, Francesco; Spagnuolo, Maria Immacolata; Candusso, M.; Melis, Daniela; Torre, Giuliano; Iorio, Raffaele

doi:10.1007/s00431-008-0732-z

Cited by 15 publications

(5 citation statements)

References 12 publications

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“…Immunocytochemical analyses in rats have verified the presence of Shank3 proteins in thymic tissue and suggest a role of Shank3 in the coordination of immune cell signal transduction [54]. Previous case reports have also suggested a link between immune dysfunction and SHANK3 deficiency [55,56]. Our findings suggest an increased prevalence of recurring infections in our sample of patients with SHANK3 deficiency and its relationship to SHANK3 and neighboring genes is an area that should be more carefully explored in the future.…”

Section: Discussionmentioning

confidence: 99%

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

et al. 2013

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Background22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is a neurodevelopmental disorder characterized by intellectual disability, hypotonia, delayed or absent speech, and autistic features. SHANK3 has been identified as the critical gene in the neurological and behavioral aspects of this syndrome. The phenotype of SHANK3 deficiency has been described primarily from case studies, with limited evaluation of behavioral and cognitive deficits. The present study used a prospective design and inter-disciplinary clinical evaluations to assess patients with SHANK3 deficiency, with the goal of providing a comprehensive picture of the medical and behavioral profile of the syndrome.MethodsA serially ascertained sample of patients with SHANK3 deficiency (n = 32) was evaluated by a team of child psychiatrists, neurologists, clinical geneticists, molecular geneticists and psychologists. Patients were evaluated for autism spectrum disorder using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-G.ResultsThirty participants with 22q13.3 deletions ranging in size from 101 kb to 8.45 Mb and two participants with de novo SHANK3 mutations were included. The sample was characterized by high rates of autism spectrum disorder: 27 (84%) met criteria for autism spectrum disorder and 24 (75%) for autistic disorder. Most patients (77%) exhibited severe to profound intellectual disability and only five (19%) used some words spontaneously to communicate. Dysmorphic features, hypotonia, gait disturbance, recurring upper respiratory tract infections, gastroesophageal reflux and seizures were also common. Analysis of genotype-phenotype correlations indicated that larger deletions were associated with increased levels of dysmorphic features, medical comorbidities and social communication impairments related to autism. Analyses of individuals with small deletions or point mutations identified features related to SHANK3 haploinsufficiency, including ASD, seizures and abnormal EEG, hypotonia, sleep disturbances, abnormal brain MRI, gastroesophageal reflux, and certain dysmorphic features.ConclusionsThis study supports findings from previous research on the severity of intellectual, motor, and speech impairments seen in SHANK3 deficiency, and highlights the prominence of autism spectrum disorder in the syndrome. Limitations of existing evaluation tools are discussed, along with the need for natural history studies to inform clinical monitoring and treatment development in SHANK3 deficiency.

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Section: Discussionmentioning

confidence: 99%

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

et al. 2013

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“…Recently, Tufano et al . reported on female patients with fulminant AIH due to the 23q13 deletion syndrome, including a disruption of the ProSAP2 gene known as the Shank3 gene 31 . In their report, a typical AIH associated with periportal inflammation was diagnosed based on histological findings which were different from those of acute presentation of AIH, but further studies are necessary to determine whether such histological findings are the risk factor for progressing to the serious disease.…”

Section: Cases Presenting With Fulminant Hepatitis and Acute Hepatic mentioning

confidence: 99%

Acute presentation of autoimmune hepatitis: Does it exist? A published work review

Takahashi

Zeniya

2011

Hepatology Research

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Autoimmune hepatitis (AIH), initially called chronic aggressive hepatitis, is conceptually classified as a primary chronic disease; periportal fibrous expansion and periportal infiltration of mononuclear cells, including plasma cells, have also been considered to be histologically important diagnostic signs of AIH. However, several manuscripts which reported the acute presentation of AIH have been published recently and the reported cases of acute presentation in these manuscripts contained two different clinical entities. One is acute exacerbation of chronic AIH (acute exacerbation form) and the other is genuine acute AIH without chronic histological changes (acute form). It is clinically important to distinguish the acute form from the acute exacerbation form. The reports of the acute form revealed that the existence of centrilobular necrosis without chronic changes was the most important histological finding related to the acute form. Because the elevation of serum levels of immunoglobulin G and antinuclear antibody are not observed in some acute presentation AIH patients, the physician may not consider AIH when they encounter such patients. Therefore, it is very important to bear in mind a possibility of acute presentation AIH when the physician encounters patients with hepatic dysfunction of unknown cause because it became clear that delay of the diagnosis and start of therapy lead to the poor prognosis of AIH. In this review, we outline the current state of acute presentation of AIH including the genuine acute form based on the published clinical studies and case reports.

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“…Feeding difficulties are likewise common [ 30 , 37 ] and may be related to low muscle tone. There have also been two reported cases of fulminant autoimmune hepatitis in girls with PMS [ 58 , 59 ]. Gastrointestinal symptoms can be highly distressing and may manifest as appetite or behavioral changes in patients who cannot describe or identify their discomfort.…”

Section: Reviewmentioning

confidence: 99%

“…There is also evidence from animal studies that SHANK3 protein may play a role in immune function, including immune cell signal transduction [ 60 ]. Children with PMS may suffer from immunological dysfunction based on case reports of autoimmune hepatitis [ 58 , 59 ], atopic dermatitis [ 61 ], and recurring staphylococcus skin infections with a history of cellulitis [ 37 ]. Sarasua and colleagues [ 39 ] found cellulitis in 9 out of 137 (7%) patients.…”

Section: Reviewmentioning

confidence: 99%

Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring

Kolevzon

Angarita

Bush

et al. 2014

J Neurodevelop Disord

136

142

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Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes. One example is SHANK3 on the terminal end of chromosome 22q. Loss of one functional copy of SHANK3 results in 22q13 deletion syndrome or Phelan-McDermid syndrome (PMS) and causes a monogenic form of ASD and/or ID with a frequency of 0.5% to 2% of cases. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. With chromosomal microarray analyses now a standard of care in the assessment of ASD and developmental delay, and with the emergence of whole exome and whole genome sequencing in this context, identification of PMS in routine clinical settings will increase significantly. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. Evaluations must include a thorough history and physical and dysmorphology examination. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Endocrine, renal, cardiac, and gastrointestinal problems all require assessment and monitoring in addition to the risk of recurring infections, dental and vision problems, and lymphedema. Finally, all patients should have cognitive, behavioral, and ASD evaluations. The objective of this paper is to address this gap in the literature and establish recommendations to assess the medical, genetic, and neurological features of PMS.

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Fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome: a previously unreported association

Cited by 15 publications

References 12 publications

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency

Acute presentation of autoimmune hepatitis: Does it exist? A published work review

Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring

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