Medicine:Ventricular extrasystoles with syncopal episodes-perodactyly-Robin sequence syndrome

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Ventricular extrasystoles with syncopal episodes-perodactyly-Robin sequence syndrome
Other namesVentricular extrasystoles with syncope, perodactyly, and Robin sequence, Stoll-Kieny-Dott syndrome, Ventricular extrasystoles perodactyly Robin sequence[1]
Autosomal dominant - en.svg
SpecialtyMedical genetics
Usual onsetBirth and Childhood
CausesGenetic mutation
Preventionnone
Frequencyrare
Deaths-

Ventricular extrasystoles with syncopal episodes-perodactyly-Robin sequence syndrome is a rare autosomal dominant genetic disorder characterized by cardiofaciodigital anomalies occurring alongside Pierre Robin sequence.[2] Additional features include abnormal sense of smell, camptodactyly, recurrent joint dislocations, and short stature.[3] Around 6 to 12 cases have been described in medical literature.[4][5]

This condition has also been called heart-hand syndrome type 5.[6]

Cases

This condition was first discovered in 1992 by Stoll et al, when they described 6 members belonging to a 3-generation France family. They had ventricular extrasystoles that presented itself with syncopal episodes associated with multifocal tachycardia, aplastic/hypoplastic distal phalanges of the toes (a phenomenon Stoll et al. described as perodactyly), Pierre Robin Sequence, a condition which causes symptoms such as glossoptosis, and down-slanting palpebral fissures (which Stoll et al. described as antimongoloid slanted). One instance of male-to-male transmission was seen in the family.[7]

In 2008, Mercer et al. described 5 cases from 2 families. The first case was from a 7-year-old United Kingdom girl who was brought to a doctor visit after she had a syncopal episode (also known as fainting) while swimming. Physical examination showed that she had similar symptoms to those shown by the French family reported by Stoll et al. The second to fifth cases were from 4 members of a 2-generation English family (a woman, her brother, and her two sons), alongside the typical symptoms of the syndrome, they also had other dysmorphic features such as a straight, pointy nose and prominent interphalangeal joints. Out of the 4 patients, 3 had hypodontia, 2 had multiple ventricular extrasystoles that weren't associated with syncopal episodes, 2 had microcephaly, the same 2 patients had a low anterior hairline, and the same 2 patients had mild learning difficulties. These last 2 cases (with microcephaly, low anterior hairline and learning difficulties) were from the brothers, they attended a special needs school. While the mother didn't have any learning difficulties and had average intelligence, she did report having had difficulties with school during her academic years.[8] A follow-up on the family was reported by Pengelly et al in the year 2016: one of the 2 brothers went on to have a daughter who reportedly had additional multiple congenital anomalies/dysmorphic features which neither of the brothers had been reported of having, including agenesis of the first metacarpal, a mild form of developmental delay, speech delay, long philtrum, short nasal bridge, thin upper lip, epicanthic folds, radial agenesis of the right arm, thumb hypoplasia, and various benign septal defects (of the heart) which were deemed to be harmless. Genetic testing revealed that all 5 family members that had once been reported as having Stoll syndrome had a mutation in their TRIO gene, which indicated that they had a separate disorder known as autosomal dominant intellectual disability-44 with microcephaly[9]

Autosomal dominant intellectual disability-44 with microcephaly

This is a condition with only around 25 cases described in medical history (including the previously mentioned family), it's characterized by mild intellectual disability and developmental delay, microcephaly, digital anomalies, and facial dysmorphisms. It is associated with heterozygous mutations in the TRIO gene.[10]

References

  1. "Ventricular extrasystoles with syncopal episodes-perodactyly-Robin sequence syndrome". https://rarediseases.org/gard-rare-disease/ventricular-extrasystoles-with-syncopal-episodes-perodactyly-robin-sequence/. 
  2. "Ventricular extrasystoles with syncopal episodes-perodactyly-robin sequence syndrome (Concept Id: C1860471) - MedGen - NCBI" (in en). https://www.ncbi.nlm.nih.gov/medgen/395493. 
  3. "Ventricular extrasystoles with syncopal episodes - perodactyly - Robin sequence - About the Disease - Genetic and Rare Diseases Information Center" (in en). https://rarediseases.info.nih.gov/diseases/5472/ventricular-extrasystoles-with-syncopal-episodes-perodactyly-robin-sequence. 
  4. RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Ventricular extrasystoles with syncopal episodes perodactyly Robin sequence syndrome" (in en). https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=3201. 
  5. "Entry - 192445 - VENTRICULAR EXTRASYSTOLES WITH SYNCOPE, PERODACTYLY, AND ROBIN SEQUENCE - OMIM" (in en-us). https://www.omim.org/entry/192445#3. 
  6. Toriello, H. V. New syndromes: heart-hand syndrome V. Dysmorph. Clin. Genet. 6: 41 only, 1992.
  7. Stoll, C.; Kieny, J. R.; Dott, B.; Alembik, Y.; Finck, S. (1992-02-15). "Ventricular extrasystoles with syncopal episodes, perodactyly, and Robin in sequence in three generations: a new inherited MCA syndrome?". American Journal of Medical Genetics 42 (4): 480–486. doi:10.1002/ajmg.1320420413. ISSN 0148-7299. PMID 1376967. https://pubmed.ncbi.nlm.nih.gov/1376967/. 
  8. Mercer, Catherine L.; Keeton, Barry; Dennis, Nicolas R. (April 2008). "Familial multiple ventricular extrasystoles, short stature, craniofacial abnormalities and digital hypoplasia: a further case of Stoll syndrome?". Clinical Dysmorphology 17 (2): 91–93. doi:10.1097/MCD.0b013e3282efefc9. ISSN 0962-8827. PMID 18388777. https://pubmed.ncbi.nlm.nih.gov/18388777/. 
  9. Pengelly, Reuben J.; Greville-Heygate, Stephanie; Schmidt, Susanne; Seaby, Eleanor G.; Jabalameli, M. Reza; Mehta, Sarju G.; Parker, Michael J.; Goudie, David et al. (November 2016). "Mutations specific to the Rac-GEF domain of TRIO cause intellectual disability and microcephaly". Journal of Medical Genetics 53 (11): 735–742. doi:10.1136/jmedgenet-2016-103942. ISSN 1468-6244. PMID 27418539. PMC 5264232. https://pubmed.ncbi.nlm.nih.gov/27418539/. 
  10. "Entry - #617061 - INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 44, WITH MICROCEPHALY; MRD44 - OMIM" (in en-us). https://www.omim.org/entry/617061#4.