Specific congenital heart defects in RSH/Smith-Lemli-Opitz syndrome

Postulated involvement of the sonic hedgehog pathway in syndromes with postaxial polydactyly or heterotaxia

Maria Cristina Digilio, Bruno Marino, Aldo Giannotti, Bruno Dallapiccola, John M. Opitz

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

BACKGROUND: RSH/Smith-Lemli-Opitz syndrome is an autosomal recessive syndrome due to an inborn error of cholesterol metabolism and is characterized by developmental delay, facial anomalies, hypospadias, congenital heart defect (CHD), postaxial polydactyly, and 2-3 toe syndactyly. CHD is found in half of the propositi, and a specific association with atrioventricular canal defect (AVCD) and anomalous pulmonary venous return has been demonstrated. METHODS: We report on an additional patient with RSH/SLOS presenting with complete AVCD and anomalous pulmonary venous return, and discuss the possible relationship of the Sonic Hedgehog (SHH) pathway as causative factor of these CHDs and those in heterotaxia patients with postaxial polydactyly syndromes. RESULTS: Anatomic similarities between heterotaxia and CHDs of several syndromes with postaxial polydactyly have been noted previously, considering the frequent association of AVCD with common atrium in these conditions. It is known that both CHDs of heterotaxia and postaxial polydactyly can be related to abnormalities of the SHH pathway. Cholesterol has a critical role in the formation of normally active hedgehog proteins. It could be hypothesized that specific types of CHDs in RSH/SLOS can be caused by modifications of the SHH protein related to the defect of cholesterol biosynthesis. CONCLUSIONS: The specific association of AVCD and anomalous pulmonary venous return in patients with RSH/SLOS and the finding of AVCD ± common atrium in several syndromes with polydactyly leads to the hypothesis that heterotaxia due to SHH anomalies could be involved in a large spectrum of conditions. Perturbations in different components of the SHH pathway could lead to several developmental errors presenting with partially overlapping clinical manifestations.

Original languageEnglish
Pages (from-to)149-153
Number of pages5
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume67
Issue number3
DOIs
Publication statusPublished - Mar 1 2003

Fingerprint

Smith-Lemli-Opitz Syndrome
Congenital Heart Defects
Scimitar Syndrome
Hedgehog Proteins
Cholesterol
Syndactyly
Polydactyly
Inborn Errors Metabolism
Hypospadias
Toes
Postaxial Polydactyly
Atrioventricular Septal Defect

ASJC Scopus subject areas

  • Developmental Biology

Cite this

@article{b2f75f50242f4687b3ea142696f9731d,
title = "Specific congenital heart defects in RSH/Smith-Lemli-Opitz syndrome: Postulated involvement of the sonic hedgehog pathway in syndromes with postaxial polydactyly or heterotaxia",
abstract = "BACKGROUND: RSH/Smith-Lemli-Opitz syndrome is an autosomal recessive syndrome due to an inborn error of cholesterol metabolism and is characterized by developmental delay, facial anomalies, hypospadias, congenital heart defect (CHD), postaxial polydactyly, and 2-3 toe syndactyly. CHD is found in half of the propositi, and a specific association with atrioventricular canal defect (AVCD) and anomalous pulmonary venous return has been demonstrated. METHODS: We report on an additional patient with RSH/SLOS presenting with complete AVCD and anomalous pulmonary venous return, and discuss the possible relationship of the Sonic Hedgehog (SHH) pathway as causative factor of these CHDs and those in heterotaxia patients with postaxial polydactyly syndromes. RESULTS: Anatomic similarities between heterotaxia and CHDs of several syndromes with postaxial polydactyly have been noted previously, considering the frequent association of AVCD with common atrium in these conditions. It is known that both CHDs of heterotaxia and postaxial polydactyly can be related to abnormalities of the SHH pathway. Cholesterol has a critical role in the formation of normally active hedgehog proteins. It could be hypothesized that specific types of CHDs in RSH/SLOS can be caused by modifications of the SHH protein related to the defect of cholesterol biosynthesis. CONCLUSIONS: The specific association of AVCD and anomalous pulmonary venous return in patients with RSH/SLOS and the finding of AVCD ± common atrium in several syndromes with polydactyly leads to the hypothesis that heterotaxia due to SHH anomalies could be involved in a large spectrum of conditions. Perturbations in different components of the SHH pathway could lead to several developmental errors presenting with partially overlapping clinical manifestations.",
author = "Digilio, {Maria Cristina} and Bruno Marino and Aldo Giannotti and Bruno Dallapiccola and Opitz, {John M.}",
year = "2003",
month = "3",
day = "1",
doi = "10.1002/bdra.10010",
language = "English",
volume = "67",
pages = "149--153",
journal = "Teratology",
issn = "1542-0752",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Specific congenital heart defects in RSH/Smith-Lemli-Opitz syndrome

T2 - Postulated involvement of the sonic hedgehog pathway in syndromes with postaxial polydactyly or heterotaxia

AU - Digilio, Maria Cristina

AU - Marino, Bruno

AU - Giannotti, Aldo

AU - Dallapiccola, Bruno

AU - Opitz, John M.

PY - 2003/3/1

Y1 - 2003/3/1

N2 - BACKGROUND: RSH/Smith-Lemli-Opitz syndrome is an autosomal recessive syndrome due to an inborn error of cholesterol metabolism and is characterized by developmental delay, facial anomalies, hypospadias, congenital heart defect (CHD), postaxial polydactyly, and 2-3 toe syndactyly. CHD is found in half of the propositi, and a specific association with atrioventricular canal defect (AVCD) and anomalous pulmonary venous return has been demonstrated. METHODS: We report on an additional patient with RSH/SLOS presenting with complete AVCD and anomalous pulmonary venous return, and discuss the possible relationship of the Sonic Hedgehog (SHH) pathway as causative factor of these CHDs and those in heterotaxia patients with postaxial polydactyly syndromes. RESULTS: Anatomic similarities between heterotaxia and CHDs of several syndromes with postaxial polydactyly have been noted previously, considering the frequent association of AVCD with common atrium in these conditions. It is known that both CHDs of heterotaxia and postaxial polydactyly can be related to abnormalities of the SHH pathway. Cholesterol has a critical role in the formation of normally active hedgehog proteins. It could be hypothesized that specific types of CHDs in RSH/SLOS can be caused by modifications of the SHH protein related to the defect of cholesterol biosynthesis. CONCLUSIONS: The specific association of AVCD and anomalous pulmonary venous return in patients with RSH/SLOS and the finding of AVCD ± common atrium in several syndromes with polydactyly leads to the hypothesis that heterotaxia due to SHH anomalies could be involved in a large spectrum of conditions. Perturbations in different components of the SHH pathway could lead to several developmental errors presenting with partially overlapping clinical manifestations.

AB - BACKGROUND: RSH/Smith-Lemli-Opitz syndrome is an autosomal recessive syndrome due to an inborn error of cholesterol metabolism and is characterized by developmental delay, facial anomalies, hypospadias, congenital heart defect (CHD), postaxial polydactyly, and 2-3 toe syndactyly. CHD is found in half of the propositi, and a specific association with atrioventricular canal defect (AVCD) and anomalous pulmonary venous return has been demonstrated. METHODS: We report on an additional patient with RSH/SLOS presenting with complete AVCD and anomalous pulmonary venous return, and discuss the possible relationship of the Sonic Hedgehog (SHH) pathway as causative factor of these CHDs and those in heterotaxia patients with postaxial polydactyly syndromes. RESULTS: Anatomic similarities between heterotaxia and CHDs of several syndromes with postaxial polydactyly have been noted previously, considering the frequent association of AVCD with common atrium in these conditions. It is known that both CHDs of heterotaxia and postaxial polydactyly can be related to abnormalities of the SHH pathway. Cholesterol has a critical role in the formation of normally active hedgehog proteins. It could be hypothesized that specific types of CHDs in RSH/SLOS can be caused by modifications of the SHH protein related to the defect of cholesterol biosynthesis. CONCLUSIONS: The specific association of AVCD and anomalous pulmonary venous return in patients with RSH/SLOS and the finding of AVCD ± common atrium in several syndromes with polydactyly leads to the hypothesis that heterotaxia due to SHH anomalies could be involved in a large spectrum of conditions. Perturbations in different components of the SHH pathway could lead to several developmental errors presenting with partially overlapping clinical manifestations.

UR - http://www.scopus.com/inward/record.url?scp=0141891471&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141891471&partnerID=8YFLogxK

U2 - 10.1002/bdra.10010

DO - 10.1002/bdra.10010

M3 - Article

VL - 67

SP - 149

EP - 153

JO - Teratology

JF - Teratology

SN - 1542-0752

IS - 3

ER -