Tags

Type your tag names separated by a space and hit enter

Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation.
Eur J Pediatr 2004; 163(7):347-52EJ

Abstract

Mutations in the human sonic hedgehog gene (SHH) are the most frequent cause of autosomal dominant inherited holoprosencephaly (HPE), a complex brain malformation resulting from incomplete cleavage of the developing forebrain into two separate hemispheres and ventricles. Here we report the clinical and molecular findings in five unrelated patients with HPE and their relatives with an identified SHH mutation. Three new and one previously reported SHH mutations were identified, a fifth proband was found to carry a reciprocal subtelomeric rearrangement involving the SHH locus in 7q36. An extremely wide intrafamilial phenotypic variability was observed, ranging from the classical phenotype with alobar HPE accompanied by typical severe craniofacial abnormalities to very mild clinical signs of choanal stenosis or solitary median maxillary central incisor (SMMCI) only. Two families were initially ascertained because of microcephaly in combination with developmental delay and/or mental retardation and SMMCI, the latter being a frequent finding in patients with an identified SHH mutation. In other affected family members a delay in speech acquisition and learning disabilities were the leading clinical signs.

CONCLUSION

mutational analysis of the sonic hedgehog gene should not only be considered in patients presenting with the classical holoprosencephaly phenotype but also in those with two or more clinical signs of the wide phenotypic spectrum of associated abnormalities, especially in combination with a positive family history.

Authors+Show Affiliations

Centre for Gynaecological Endocrinology, Reproductive Medicine and Human Genetics, Hemauerstrasse 1, 93047 Regensburg, Germany. ute.hehr@humangenetik-regensburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

15107988

Citation

Hehr, Ute, et al. "Wide Phenotypic Variability in Families With Holoprosencephaly and a Sonic Hedgehog Mutation." European Journal of Pediatrics, vol. 163, no. 7, 2004, pp. 347-52.
Hehr U, Gross C, Diebold U, et al. Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation. Eur J Pediatr. 2004;163(7):347-52.
Hehr, U., Gross, C., Diebold, U., Wahl, D., Beudt, U., Heidemann, P., ... Mueller, D. (2004). Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation. European Journal of Pediatrics, 163(7), pp. 347-52.
Hehr U, et al. Wide Phenotypic Variability in Families With Holoprosencephaly and a Sonic Hedgehog Mutation. Eur J Pediatr. 2004;163(7):347-52. PubMed PMID: 15107988.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation. AU - Hehr,Ute, AU - Gross,Claudia, AU - Diebold,Uta, AU - Wahl,Dagmar, AU - Beudt,Ulrike, AU - Heidemann,Peter, AU - Hehr,Andreas, AU - Mueller,Dietmar, Y1 - 2004/04/24/ PY - 2003/12/23/received PY - 2004/03/14/revised PY - 2004/03/19/accepted PY - 2004/4/27/pubmed PY - 2004/12/16/medline PY - 2004/4/27/entrez SP - 347 EP - 52 JF - European journal of pediatrics JO - Eur. J. Pediatr. VL - 163 IS - 7 N2 - UNLABELLED: Mutations in the human sonic hedgehog gene (SHH) are the most frequent cause of autosomal dominant inherited holoprosencephaly (HPE), a complex brain malformation resulting from incomplete cleavage of the developing forebrain into two separate hemispheres and ventricles. Here we report the clinical and molecular findings in five unrelated patients with HPE and their relatives with an identified SHH mutation. Three new and one previously reported SHH mutations were identified, a fifth proband was found to carry a reciprocal subtelomeric rearrangement involving the SHH locus in 7q36. An extremely wide intrafamilial phenotypic variability was observed, ranging from the classical phenotype with alobar HPE accompanied by typical severe craniofacial abnormalities to very mild clinical signs of choanal stenosis or solitary median maxillary central incisor (SMMCI) only. Two families were initially ascertained because of microcephaly in combination with developmental delay and/or mental retardation and SMMCI, the latter being a frequent finding in patients with an identified SHH mutation. In other affected family members a delay in speech acquisition and learning disabilities were the leading clinical signs. CONCLUSION: mutational analysis of the sonic hedgehog gene should not only be considered in patients presenting with the classical holoprosencephaly phenotype but also in those with two or more clinical signs of the wide phenotypic spectrum of associated abnormalities, especially in combination with a positive family history. SN - 0340-6199 UR - https://www.unboundmedicine.com/medline/citation/15107988/Wide_phenotypic_variability_in_families_with_holoprosencephaly_and_a_sonic_hedgehog_mutation_ L2 - https://dx.doi.org/10.1007/s00431-004-1459-0 DB - PRIME DP - Unbound Medicine ER -