#Pica syndrome radiopaedia series#

Reports highlight a broad and clinically heterogeneous phenotype clinical features consistently reported include global developmental delay, absent or severely delayed speech, autistic features, minor dysmorphic features, and hypotonia.

#Pica syndrome radiopaedia series#

While some clinical guidelines exist, comprehensive medical assessment parameters have yet to be developed.Ĭlinically, there have been at least 13 case series published in the literature that describe approximately 584 affected individuals (see Tables 1 and 2), although several studies present overlapping cases and the majority of data has been collected using parent surveys. To date, about 1,200 cases have been identified worldwide according to the Phelan-McDermid Syndrome Foundation, yet few physicians have encountered the syndrome. With chromosomal microarray now recommended as a standard of care for the assessment of ASD, it is expected that identification of PMS will increase significantly in routine clinical settings. Interestingly, reversal of synaptic deficits has been shown with an experimental therapeutic (insulin-like growth factor-1 IGF-1) in mouse and human neuronal models. Using Shank3-deficient mice, specific deficits in synaptic function and plasticity in glutamatergic signaling have been documented. Although SHANK3 deletions and mutations account for a relatively small proportion of ASD and ID cases, recent evidence suggests that many different genetic causes of ASD and ID converge on several common pathways, including the SHANK3 pathway. SHANK3 encodes a scaffolding protein in the postsynaptic density of glutamatergic synapses and is known to play a critical role in synaptic function. SHANK3 is the critical gene in this syndrome, and its loss is sufficient to cause Phelan-McDermid syndrome (PMS OMIM ID 606232). The rate of SHANK3 loss in children with moderate to profound intellectual disability (ID) appears to be up to 2%. Studies indicate that loss of one functional copy (haploinsufficiency) of SHANK3 through deletion or mutation causes a monogenic form of ASD with a frequency of at least 0.5% of ASD cases. ASD can now be conceived of as having many distinct genetic risk genes and one example is SHANK3 on terminal chromosome 22q. Gene discovery approaches, followed by functional analysis of model systems, have elucidated the neurobiology of several genetic subtypes of autism spectrum disorder (ASD). 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. Finally, all patients should have cognitive, behavioral, and ASD evaluations. 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. Neurological deficits, including the presence of seizures and structural brain abnormalities should be assessed as well as motor deficits. Evaluations must include a thorough history and physical and dysmorphology examination. While there is agreement about core deficits of PMS, there have been no established parameters to guide evaluation and medical monitoring of the syndrome. However, PMS remains a rare disorder, and the majority of physicians have never seen a case. 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. SHANK3 is the critical gene in this syndrome, and its loss results in disruption of synaptic function. 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. One example is SHANK3 on the terminal end of chromosome 22q. Autism spectrum disorder (ASD) and intellectual disability (ID) can be caused by mutations in a large number of genes.