TY - JOUR
T1 - Proposal of a clinical score for the molecular test for Pitt-Hopkins syndrome
AU - Marangi, Giuseppe
AU - Battaglia, Domenica Immacolata
AU - Zollino, Marcella
AU - Ricciardi, Stefania
AU - Orteschi, Daniela
AU - Lettori, Donatella
AU - Vasco, Gessica
AU - Tenconi, R
AU - Monica, Md
AU - Scarano, G
PY - 2012
Y1 - 2012
N2 - Pitt–Hopkins syndrome (PTHS) is an emerging condition characterized by severe intellectual disability (ID), typical facial gestalt, and additional features, such as breathing abnormalities. Because of the overlapping phenotype of severe ID with absent speech, epilepsy, microcephaly, large mouth, and constipation, differential diagnosis of PTHS with respect to Angelman, Rett, and Mowat–Wilson syndromes represents a relevant clinical issue, and many patients are currently undergoing genetic tests for different conditions that are assumed to fall within the PTHS clinical spectrum. During a search for TCF4 mutations in 78 patients with a suspected PTHS, haploinsufficiency of TCF4 was identified in 18. By evaluating clinical features of patients with a proven TCF4 mutation with those of patients without, we noticed that, in addition to the typical facial gestalt, the PTHS phenotype results from the various combination of the following characteristics: ID with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing abnormalities, motor incoordination, ocular anomalies, constipation, seizures, typical behavior, and subtle brain abnormalities. On the basis of these observations, here we propose a clinically based score system as useful tool for driving a first choice molecular test for PTHS. This scoring system is also proposed for a clinically based diagnosis of PTHS in absence of a proven TCF4 mutation
AB - Pitt–Hopkins syndrome (PTHS) is an emerging condition characterized by severe intellectual disability (ID), typical facial gestalt, and additional features, such as breathing abnormalities. Because of the overlapping phenotype of severe ID with absent speech, epilepsy, microcephaly, large mouth, and constipation, differential diagnosis of PTHS with respect to Angelman, Rett, and Mowat–Wilson syndromes represents a relevant clinical issue, and many patients are currently undergoing genetic tests for different conditions that are assumed to fall within the PTHS clinical spectrum. During a search for TCF4 mutations in 78 patients with a suspected PTHS, haploinsufficiency of TCF4 was identified in 18. By evaluating clinical features of patients with a proven TCF4 mutation with those of patients without, we noticed that, in addition to the typical facial gestalt, the PTHS phenotype results from the various combination of the following characteristics: ID with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing abnormalities, motor incoordination, ocular anomalies, constipation, seizures, typical behavior, and subtle brain abnormalities. On the basis of these observations, here we propose a clinically based score system as useful tool for driving a first choice molecular test for PTHS. This scoring system is also proposed for a clinically based diagnosis of PTHS in absence of a proven TCF4 mutation
KW - Clinical Checklist
KW - Pitt–Hopkins Syndrome
KW - TCF4
KW - Clinical Checklist
KW - Pitt–Hopkins Syndrome
KW - TCF4
UR - http://hdl.handle.net/10807/7138
U2 - 10.1002/ajmg.a.35419
DO - 10.1002/ajmg.a.35419
M3 - Article
SP - n/a-n/a
JO - AMERICAN JOURNAL OF MEDICAL GENETICS. PART A
JF - AMERICAN JOURNAL OF MEDICAL GENETICS. PART A
SN - 1552-4825
ER -