Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients.
BACKGROUND
Haploinsufficiency of the gene encoding for transcription factor 4 (TCF4) was recently identified as the underlying cause of Pitt-Hopkins syndrome (PTHS), an underdiagnosed mental-retardation syndrome characterised by a distinct facial gestalt, breathing anomalies and severe mental retardation.


METHODS
TCF4 mutational analysis was performed in 117 patients with PTHS-like features.


RESULTS
In total, 16 novel mutations were identified. All of these proven patients were severely mentally retarded and showed a distinct facial gestalt. In addition, 56% had breathing anomalies, 56% had microcephaly, 38% had seizures and 44% had MRI anomalies.


CONCLUSIONS
This study provides further evidence of the mutational and clinical spectrum of PTHS and confirms its important role in the differential diagnosis of severe mental retardation.
Zweier
C
C
Sticht
H
H
Bijlsma
E K
EK
Clayton-Smith
J
J
Boonen
S E
SE
Fryer
A
A
Greally
M T
MT
Hoffmann
L
L
den Hollander
N S
NS
Jongmans
M
M
Kant
S G
SG
King
M D
MD
Lynch
S A
SA
McKee
S
S
Midro
A T
AT
Park
S-M
SM
Ricotti
V
V
Tarantino
E
E
Wessels
M
M
Peippo
M
M
Rauch
A
A
D000293:Adolescent; D001049:Apnea / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005145:Face / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D006985:Hyperventilation / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008831:Microcephaly; D010641:Phenotype; D013577:Syndrome; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors