Abstract
Because it is unclear whether the genotype may influence the clinical course in patients with LEOPARD syndrome (LS), we analyzed clinical and molecular predictors of adverse cardiac events in patients with left ventricular hypertrophy (LVH). A comprehensive cardiovascular evaluation, including baseline electrocardiogram, echocardiography, exercise test and 24 hr Holter monitoring at the time of clinical diagnosis and during follow-up was conducted on 24 patients referred to our departments. Phenotypical examination and diagnosis were performed by expert clinical geneticists. The entire PTPN11 and RAF1 coding regions were screened for mutations by DHPLC analysis, followed by sequencing. Patients without PTPN11 mutations (34%) showed a higher frequency of family history of sudden death (P = 0.007), increased left atrial dimensions (P = 0.05), bradyarrhythmias (P = 0.04), episodes of supraventricular tachycardias (P = 0.06), atrial fibrillation (P = 0.009), and nonsustained ventricular tachycardias (P = 0.05) during Holter monitoring. Six patients (25%) had adverse cardiac events during follow-up (including sudden deaths, resuscitated cardiac arrest, septal myectomy, and heart failure). LVH, New York Heart Association Class, left ventricular outflow tract obstruction, and nonsustained ventricular tachycardias were associated to adverse cardiac events. Of note, three patients with mutations in exon 13 showed a severe obstructive cardiomyopathy, with serious cardiac complications during follow-up (heart failure, septal myectomy, and sudden death). In conclusion, patients with LVH associated with LS seem to carry a relatively high risk of adverse (arrhythmic and nonarrhythmic) events. Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH.
| Original language | English |
|---|---|
| Pages (from-to) | 620-628 |
| Number of pages | 9 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 146 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 1 2008 |
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Keywords
- Clinical outcome
- Left ventricular hypertrophy
- LEOPARD syndrome
- PTPN11 mutations
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
- Medicine(all)
Cite this
Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome. / Limongelli, Giuseppe; Sarkozy, Anna; Pacileo, Giuseppe; Calabrò, Paolo; Digilio, Maria Cristina; Maddaloni, Valeria; Gagliardi, Giulia; Di Salvo, Giovanni; Iacomino, Maria; Marino, Bruno; Dallapiccola, Bruno; Calabrò, Raffaele.
In: American Journal of Medical Genetics, Part A, Vol. 146, No. 5, 01.03.2008, p. 620-628.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome
AU - Limongelli, Giuseppe
AU - Sarkozy, Anna
AU - Pacileo, Giuseppe
AU - Calabrò, Paolo
AU - Digilio, Maria Cristina
AU - Maddaloni, Valeria
AU - Gagliardi, Giulia
AU - Di Salvo, Giovanni
AU - Iacomino, Maria
AU - Marino, Bruno
AU - Dallapiccola, Bruno
AU - Calabrò, Raffaele
PY - 2008/3/1
Y1 - 2008/3/1
N2 - Because it is unclear whether the genotype may influence the clinical course in patients with LEOPARD syndrome (LS), we analyzed clinical and molecular predictors of adverse cardiac events in patients with left ventricular hypertrophy (LVH). A comprehensive cardiovascular evaluation, including baseline electrocardiogram, echocardiography, exercise test and 24 hr Holter monitoring at the time of clinical diagnosis and during follow-up was conducted on 24 patients referred to our departments. Phenotypical examination and diagnosis were performed by expert clinical geneticists. The entire PTPN11 and RAF1 coding regions were screened for mutations by DHPLC analysis, followed by sequencing. Patients without PTPN11 mutations (34%) showed a higher frequency of family history of sudden death (P = 0.007), increased left atrial dimensions (P = 0.05), bradyarrhythmias (P = 0.04), episodes of supraventricular tachycardias (P = 0.06), atrial fibrillation (P = 0.009), and nonsustained ventricular tachycardias (P = 0.05) during Holter monitoring. Six patients (25%) had adverse cardiac events during follow-up (including sudden deaths, resuscitated cardiac arrest, septal myectomy, and heart failure). LVH, New York Heart Association Class, left ventricular outflow tract obstruction, and nonsustained ventricular tachycardias were associated to adverse cardiac events. Of note, three patients with mutations in exon 13 showed a severe obstructive cardiomyopathy, with serious cardiac complications during follow-up (heart failure, septal myectomy, and sudden death). In conclusion, patients with LVH associated with LS seem to carry a relatively high risk of adverse (arrhythmic and nonarrhythmic) events. Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH.
AB - Because it is unclear whether the genotype may influence the clinical course in patients with LEOPARD syndrome (LS), we analyzed clinical and molecular predictors of adverse cardiac events in patients with left ventricular hypertrophy (LVH). A comprehensive cardiovascular evaluation, including baseline electrocardiogram, echocardiography, exercise test and 24 hr Holter monitoring at the time of clinical diagnosis and during follow-up was conducted on 24 patients referred to our departments. Phenotypical examination and diagnosis were performed by expert clinical geneticists. The entire PTPN11 and RAF1 coding regions were screened for mutations by DHPLC analysis, followed by sequencing. Patients without PTPN11 mutations (34%) showed a higher frequency of family history of sudden death (P = 0.007), increased left atrial dimensions (P = 0.05), bradyarrhythmias (P = 0.04), episodes of supraventricular tachycardias (P = 0.06), atrial fibrillation (P = 0.009), and nonsustained ventricular tachycardias (P = 0.05) during Holter monitoring. Six patients (25%) had adverse cardiac events during follow-up (including sudden deaths, resuscitated cardiac arrest, septal myectomy, and heart failure). LVH, New York Heart Association Class, left ventricular outflow tract obstruction, and nonsustained ventricular tachycardias were associated to adverse cardiac events. Of note, three patients with mutations in exon 13 showed a severe obstructive cardiomyopathy, with serious cardiac complications during follow-up (heart failure, septal myectomy, and sudden death). In conclusion, patients with LVH associated with LS seem to carry a relatively high risk of adverse (arrhythmic and nonarrhythmic) events. Further genotype-phenotype studies are warranted to fully elucidate the impact of the genotype on the natural history of patients with LS and LVH.
KW - Clinical outcome
KW - Left ventricular hypertrophy
KW - LEOPARD syndrome
KW - PTPN11 mutations
UR - http://www.scopus.com/inward/record.url?scp=43049101740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43049101740&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.32206
DO - 10.1002/ajmg.a.32206
M3 - Article
VL - 146
SP - 620
EP - 628
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 5
ER -