TY - JOUR
T1 - Phelan-McDermid syndrome
T2 - A review of the literature and practice parameters for medical assessment and monitoring
AU - Kolevzon, Alexander
AU - Angarita, Benjamin
AU - Bush, Lauren
AU - Wang, A. Ting
AU - Frank, Yitzchak
AU - Yang, Amy
AU - Rapaport, Robert
AU - Saland, Jeffrey
AU - Srivastava, Shubhika
AU - Farrell, Cristina
AU - Edelmann, Lisa J.
AU - Buxbaum, Joseph D.
N1 - Publisher Copyright:
© 2014 Kolevzon et al.; licensee BioMed Central Ltd.
PY - 2014/10/8
Y1 - 2014/10/8
N2 - 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.
AB - 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.
KW - 22q13 deletion syndrome
KW - Autism
KW - Autism spectrum disorder
KW - Neurodevelopmental disorders
KW - Phelan-McDermid syndrome
KW - Practice parameters
KW - SHANK3
UR - http://www.scopus.com/inward/record.url?scp=84960111021&partnerID=8YFLogxK
U2 - 10.1186/1866-1955-6-39
DO - 10.1186/1866-1955-6-39
M3 - Review article
AN - SCOPUS:84960111021
SN - 1866-1947
VL - 6
JO - Journal of Neurodevelopmental Disorders
JF - Journal of Neurodevelopmental Disorders
IS - 1
M1 - 39
ER -