J Korean Med Sci.  2013 May;28(5):780-783. 10.3346/jkms.2013.28.5.780.

First Korean Family with a Mutation in TPM2 Associated with Sheldon-Hall Syndrome

• Ko JM
• Choi IH
• Baek GH
• Kim KW

• KMID: 1777569
• DOI: http://doi.org/10.3346/jkms.2013.28.5.780

Abstract

Sheldon-Hall syndrome (SHS) is a rare autosomal dominant, inherited arthrogryposis syndrome characterized by multiple congenital contractures of the distal limbs. To date, four genes that encode the skeletal muscle fiber complex have been confirmed as the causative genes. Mutations in MYH3 have been identified most frequently and few cases of SHS caused by TPM2 mutations have been reported worldwide. This report describes, for the first time, a Korean family with two generations of SHS resulting from a rare TPM2 mutation, p.R133W. The affected mother and daughter manifested typical facial features of SHS including a triangular face with downslanting palpebral fissures, small mouth, high arched palate, and prominent nasolabial folds, and showed camptodactyly of fingers and deformities of feet with congenital vertical tali. Generalized myopathy with relative sparing of the slow-twitch muscle fibers was also revealed by electromyography in the affected mother.

Keyword

TPM2; Tropomyosin; Sheldon-Hall Syndrome; Distal Arthrogryposis; Variable Expression

MeSH Terms

Alleles
Arthrogryposis/*genetics
Asian Continental Ancestry Group/*genetics
Exons
Female
Finger Phalanges/radiography
Foot Bones/radiography
Humans
Infant, Newborn
Mutation
Pedigree
Phenotype
Republic of Korea
Sequence Analysis, DNA
Tropomyosin/*genetics
Tropomyosin

Figure

• 

  Fig. 1 Photographs and simple radiographs of the feet of the daughter. (A, B) a calcaneovalgus deformity with congenital vertical talus in the right foot and an equinovarus deformity in the left foot were shown.

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  Fig. 2 Facial photographs and simple radiographs of the mother. (A) Facial photographs of the mother show her triangular-shaped face, prominent nasolabial folds, retrognathia, downslanting palpebral fissures, and attached earlobes. (B, C) Simple radiographs show camptodactyly and the ulnar deviation of the fingers and the talocalcaneal coalition in both feet.

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  Fig. 3 Partial sequences of the TPM2 gene show a heterozygous C>T mutation at nucleotide 397 of exon 4, causing the replacement of an arginine with a tryptophan at codon 133 in the mother (II:2) and daughter (III:1). The pedigree shows the cosegregation of this mutation with the SHS phenotype.

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