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

European Journal of Pediatrics (Impact Factor: 1.89). 01/2009; 168(2):225-227. DOI: 10.1007/s00431-008-0732-z


We report a 7-year-old girl with 22q13 deletion syndrome, 46,XX,Ish del(22)(q13.3)(ARSA-; D22S1726), who developed a fulminant
autoimmune hepatitis requiring orthotopic liver transplantation. Recently, it has been suggested that the Shank3 gene product,
whose deficiency is responsible for the features observed in this syndrome, could play a role in immunological response. Despite
an increased incidence of respiratory infections, autoimmune diseases have thus far not been reported in patients with this
syndrome. This is the first case of fulminant autoimmune hepatitis associated with the 22q13 deletion syndrome. The possible
relationships between immune system dysfunctions peculiar of this syndrome and autoimmune hepatitis are discussed.

7 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background 22q13 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. Methods A 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. Results Thirty 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. Conclusions This 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.
    Molecular Autism 06/2013; 4(1):18. DOI:10.1186/2040-2392-4-18 · 5.41 Impact Factor
  • Source
    • "panied by headaches, lethargy, and dehydration [Phelan et al., 2010]. Two recently described cases have presented with sudden and severe autoimmune liver failure requiring transplant [Tufano et al., 2009; Bartsch et al., 2010]. Bartsch et al. [2010] suggested that liver function tests should be part of the management of patients with 22q13.3 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome, is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. In addition to normal growth and a constellation of minor dysmorphic features, this syndrome is characterized by neurological deficits which include global developmental delay, moderate to severe intellectual impairment, absent or severely delayed speech, and neonatal hypotonia. In addition, more than 50% of patients show autism or autistic-like behavior, and therefore it can be classified as a syndromic form of autism spectrum disorders (ASD). The differential diagnosis includes Angelman syndrome, velocardiofacial syndrome, fragile X syndrome, and FG syndrome. Over 600 cases of 22q13.3 deletion syndrome have been documented. Most are terminal deletions of ∼100 kb to >9 Mb, resulting from simple deletions, ring chromosomes, and unbalanced translocations. Almost all of these deletions include the gene SHANK3 which encodes a scaffold protein in the postsynaptic densities of excitatory synapses, connecting membrane-bound receptors to the actin cytoskeleton. Two mouse knockout models and cell culture experiments show that SHANK3 is involved in the structure and function of synapses and support the hypothesis that the majority of 22q13.3 deletion syndrome neurological defects are due to haploinsufficiency of SHANK3, although other genes in the region may also play a role in the syndrome. The molecular connection to ASD suggests that potential future treatments may involve modulation of metabotropic glutamate receptors.
    Molecular syndromology 04/2012; 2(3-5):186-201. DOI:10.1159/000334260
  • Source
    • "Tufano et al. [12] recently reported fulminant autoimmune hepatitis in a girl with 22q13 deletion syndrome and suggested a possible relationship between immune system dysfunction and 22q13 deletion syndrome. Our patient was also associated with abnormal immunological findings in addition to neuropsychiatric abnormalities. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a 5-year-old boy with mental retardation, autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings, carrying a 7.9 Mb de novo deletion of chromosome 22q13.2→qter. This region contains the SHANK3, NCAPH2 and CYP2D6 genes which are associated with T-cell immune response. The present case provides evidence that 22q13 deletion syndrome may be associated with immune system dysfunction in addition to neuropsychiatric disorders.
    European journal of medical genetics 09/2010; 53(5):329-32. DOI:10.1016/j.ejmg.2010.06.004 · 1.47 Impact Factor
Show more