SNOMEDCT: 721014007; ORPHA: 168796;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q22 | Heart-hand syndrome, Slovenian type | 610140 | Autosomal dominant | 3 | LMNA | 150330 |
A number sign (#) is used with this entry because of evidence that Slovenian type heart-hand syndrome is caused by heterozygous mutation in the LMNA gene (150330) on chromosome 1q22.
Sinkovec et al. (2005) reported a Slovenian family with 10 affected members in 4 generations who had adult-onset progressive sinoatrial and atrioventricular conduction disease, sudden death due to ventricular tachyarrhythmia, dilated cardiomyopathy, and a unique type of brachydactyly with mild hand involvement and more severe foot involvement. Hand changes included short distal, middle, and proximal phalanges and clinodactyly; foot changes included short distal and proximal phalanges and metatarsal bones, short or absent middle phalanges, terminal symphalangism, duplication of the bases of the second metatarsals, extra ossicles, and syndactyly.
Renou et al. (2008) reexamined 5 affected and 3 unaffected members of the Slovenian family with heart-hand syndrome originally reported by Sinkovec et al. (2005) and observed overt myopathy in a 62-year-old affected female, who had proximal upper limb muscle weakness without joint contractures, myopathic EMG pattern, and slightly elevated creatine phosphokinase (CPK). Her 45-year-old niece also had myopathic pattern on EMG, but normal CPK and no overt muscle weakness; no other family members had muscle weakness or joint contractures.
Zaragoza et al. (2017) reported a family with German and Irish ancestry in which 11 members were born with 'small hands' and later developed heart disease. Photographs of the hands of the proband and his affected first cousin showed small hands with short digital rays. Hand radiographs showed shortened digital rays with no carpal anomalies, and metacarpophalangeal pattern profile analysis revealed a consistent wavy pattern with brachydactyly of all tubular bones with marked shortening of the first and third distal phalanges, second middle phalanx, and first proximal phalanx. The feet in both patients were normal. The proband had dilated cardiomyopathy and died at age 57. His daughter had syncope at age 12, his nephew had cardiogenic shock at age 27, and his sister had sudden death at age 23.
The transmission pattern of Slovenian type heart-hand syndrome in the family reported by Sinkovec et al. (2005) and Renou et al. (2008) was consistent with autosomal dominant inheritance.
Using microsatellite markers for known disease loci in a Slovenian family with a form of heart-hand syndrome, Sinkovec et al. (2005) excluded linkage to SCN5A (600163), ROR2 (602337), TBX5 (601620), and TBX3 (601621).
Renou et al. (2008) analyzed the LMNA gene in 12 members of the family with heart-hand syndrome originally reported by Sinkovec et al. (2005) and identified a heterozygous splice site mutation (150330.0045) that cosegregated with disease in 6 affected members and was not found in 100 healthy controls. A 32-year-old female mutation carrier showed only slight cardiac involvement, which led Renou et al. (2008) to consider that disease severity may be related to age as in other LNMA-related cardiac diseases.
In affected members of a family with Slovenian-type heart-hand syndrome, Zaragoza et al. (2017) identified heterozygosity for a missense mutation in the LMNA gene (R335W; 150330.0058) that segregated with the disorder in the family. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing.
Renou, L., Stora, S., Yaou, R. B., Volk, M., Sinkovec, M., Demay, L., Richard, P., Peterlin, B., Bonne, G. Heart-hand syndrome of Slovenian type: a new kind of laminopathy. (Letter) J. Med. Genet. 45: 666-671, 2008. [PubMed: 18611980] [Full Text: https://doi.org/10.1136/jmg.2008.060020]
Sinkovec, M., Petrovic, D., Volk, M., Peterlin, B. Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly: a new type of heart-hand syndrome? Clin. Genet. 68: 155-160, 2005. [PubMed: 15996213] [Full Text: https://doi.org/10.1111/j.1399-0004.2005.00476.x]
Zaragoza, M. V., Hakim, S. A., Hoang, V., Elliott, A. M. Heart-hand syndrome IV: a second family with LMNA-related cardiomyopathy and brachydactyly. (Letter) Clin. Genet. 91: 499-500, 2017. [PubMed: 27723096] [Full Text: https://doi.org/10.1111/cge.12870]