title: Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports.
abstract: BACKGROUND
  Phelan-Mc Dermid syndrome is a contiguous disorder resulting from 22q13.3 deletion implicating the SHANK3 gene. The typical phenotype includes neonatal hypotonia, moderate to severe intellectual disability, absent or delayed speech, minor dysmorphic features and autism or autistic-like behaviour. Recently, point mutations or micro-deletions of the SHANK3 gene have been identified, accompanied by a phenotype different from the initial clinically description in Phelan McDermid syndrome.
  
  
  METHODS
  Here we present two case studies with similar psychiatric and genetic diagnosis as well as similar clinical history and evolution. The two patients were diagnosed with autism spectrum disorders in childhood and presented regression with catatonia features and behavioural disorders after a stressful event during adolescence. Interestingly, both patients presented mutation/microdeletion of the SHANK3 gene, inducing a premature stop codon in exon 21. Different pharmacological treatments (antipsychotics, benzodiazepines, mood stabilizer drugs, antidepressants, and methylphenidate) failed to improve clinical symptoms and lead to multiple adverse events. In contrast, lithium therapy reversed clinical regression, stabilized behavioural symptoms and allowed patients to recover their pre-catatonia level of functioning, without significant side effects.
  
  
  CONCLUSIONS
  These cases support the hypothesis of a specific SHANK3 phenotype. This phenotype might be linked to catatonia-like deterioration for which lithium use could be an efficient treatment. Therefore, these cases provide an important contribution to the field of autism research, clinical genetics and possible pharmacological answers.
authors.affiliation: Autism Resources Center, University Child and Adolescent Psychiatry Department, Children's Hospitals of Nice CHU-Lenval, CoBTek EA7276 University of Nice Sophia Antipolis, Nice, France. serret.s@pediatrie-chulenval-nice.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Serret
authors.affiliation: Autism Resources Center, University Child and Adolescent Psychiatry Department, Children's Hospitals of Nice CHU-Lenval, CoBTek EA7276 University of Nice Sophia Antipolis, Nice, France. thummler.s@pediatrie-chulenval-nice.fr.
authors.forename: Susanne
authors.initials: S
authors.lastname: Thümmler
authors.affiliation: Autism Resources Center, University Child and Adolescent Psychiatry Department, Children's Hospitals of Nice CHU-Lenval, CoBTek EA7276 University of Nice Sophia Antipolis, Nice, France. dor.nedonsel@lenval.com.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dor
authors.affiliation: Autism Resources Center, University Child and Adolescent Psychiatry Department, Children's Hospitals of Nice CHU-Lenval, CoBTek EA7276 University of Nice Sophia Antipolis, Nice, France. vesperini.s@pediatrie-chulenval-nice.fr.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vesperini
authors.affiliation: Autism Resources Center, University Child and Adolescent Psychiatry Department, Children's Hospitals of Nice CHU-Lenval, CoBTek EA7276 University of Nice Sophia Antipolis, Nice, France. santos.a@pediatrie-chulenval-nice.fr.
authors.forename: Andreia
authors.initials: A
authors.lastname: Santos
authors.affiliation: Autism Resources Center, University Child and Adolescent Psychiatry Department, Children's Hospitals of Nice CHU-Lenval, CoBTek EA7276 University of Nice Sophia Antipolis, Nice, France. askenazy.f@pediatrie-chulenval-nice.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Askenazy
mesh_terms: D000293:Adolescent; D018692:Antimanic Agents / Q000008:administration & dosage; D014150:Antipsychotic Agents; D002389:Catatonia / Q000188:drug therapy / Q000209:etiology; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy / Q000209:etiology; D018020:Lithium Compounds / Q000008:administration & dosage*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D012043:Regression, Psychology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human