Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller's dementia infantilis, a rare subtype of autism spectrum disorder.
BACKGROUND
Deletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD). Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.


METHODS
Here, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3. The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.


CONCLUSIONS
Our present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years.
Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, UMR1163, Paris, France. anne.philippe@inserm.fr.
Anne
A
Philippe
Department of Child and Adolescent Psychiatry, APHP Hôpital Necker Enfants Malades, Paris, France. y.craus@free.fr.
Yann
Y
Craus
Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, UMR1163, Paris, France. marlene.rio@aphp.fr.
Marlène
M
Rio
Pediatric Neurology, APHP Hôpital Necker Enfants Malades, Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Paris, France. nadia.bahi-buisson@aphp.fr.
Nadia
N
Bahi-Buisson
Department of Imagery, APHP Hôpital Necker Enfants Malades, Paris, France. nathalie.boddaert@aphp.fr.
Nathalie
N
Boddaert
Department of Cytogenetic, APHP Hôpital Necker Enfants Malades, Paris, France. valerie.malan@aphp.fr.
Valérie
V
Malan
Molecular Genetics Unit, APHP Hôpital Necker Enfants Malades, Paris, France. jean-paul.bonnefont@aphp.fr.
Jean-Paul
JP
Bonnefont
CESP, INSERM U1178, Univ., Paris-Descartes, USPC, Paris, 75014, France. laurence.robel@free.fr.|APHP Hôpital Necker Enfants Malades, Paris, France. laurence.robel@free.fr.
Laurence
L
Robel
D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000523:psychology; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003704:Dementia / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D012043:Regression, Psychology
D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human