The association between preaxial polydactyly and radial longitudinal deficiency in syndromic cases: a report on nine families

Abstract

Preaxial polydactyly and radial longitudinal deficiency are usually viewed as two different entities. We present nine families with different disorders in which both preaxial polydactyly and radial longitudinal deficiency were seen in the phenotype. This indicates that both entities may be caused by the same developmental error or insult. The pathogenesis is complex and may be related to the interactions of two signalling loops: the first loop (named as the radial longitudinal deficiency loop) contains genes/proteins responsible for the development of the radial ray; and the second loop (named as the preaxial polydactyly loop) contains the Sonic Hedgehog involved in the pathogenesis of preaxial polydactyly. This entity is named as the preaxial polydactyly–radial longitudinal deficiency association and should be included in the description of the preaxial polydactyly spectrum.

Level of evidence: IV

Keywords

Preaxial polydactyly thumb duplication radial longitudinal deficiency

Get full access to this article

View all access options for this article.

References

Agochukwu

Pineda-Alvarez

Keaton

et al.

Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association. Eur J Med Genet. 2011, 54: 323–8.

Akiyama

Kawakami

Wong

Oishi

Nishinakamura

Kawakami

. SALL4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements. Proc Natl Acad Sci USA. 2015, 112: 5075–80.

Al-Qattan

(2013a) Preaxial polydactyly of the upper limb viewed as a spectrum of severity of embryonic events. Ann Plast Surg 17: 118–24.

Al-Qattan

(2013b) The ubiquitin/SUMO pathway and radial ray deficiency syndromes. Ann Plast Surg 70: 240–5.

Al-Qattan

Abou Al-Shaar

. Molecular basis of the clinical features of Holt-Oram syndrome resulting from missense and extended protein mutations of the TBX5 gene as well as TBX5 intragenic duplications. Gene. 2015, 560: 129–36.

Al-Qattan

Al Abdulkareem

Al Haiden

Al Balwi

. A novel mutation in the SHH long-range regulator (ZRS) is associated with preaxial polydactyly, triphalangeal thumb and severe radial ray deficiency. Am J Med Genet A. 2012, 158: 2610–5.

Al-Qattan

Shamseldin

Salih

Alkuraya

. GLI3-related polydactyly: a review. Clin Genet. 2017, 92: 457–66.

Bauer

Bednar

James

. Disruption of the radial/ulnar axis: congenital longitudinal deficiencies. J Hand Surg Am. 2013, 38: 2293–302.

Gabel

Michels

Nelson

Dobyns

. Thumb duplication and contralateral thumb by hypoplasia in an infant of mother with diabetes. J Hand Surg Am. 1991, 16: 133–5.

10.

Garcia-Barcelo

Wong

Lui

et al.

Identification of a HOXD13 mutation in a VACTERL patient. Am J Med Genet A. 2008, 146: 3181–5.

11.

Glanz

Fraser

. Spectrum of anomalies in Fanconi anaemia. J Med Genet. 1982, 19: 412–6.

12.

James

McCarroll

Jr Manske

. The spectrum of radial longitudinal deficiency: a modified classification. J Hand Surg Am. 1999, 24: 1145–55.

13.

Kawakami

Uchiyama

Esteban

et al.

Sall genes regulate region-specific morphogenesis in the mouse limb by modulating HOX activities. Development. 2009, 136: 585–94.

14.

Killoran

Abbott

McKusick

Biesecker

. Overlap of PIV syndrome, VACTERL and Pallister-Hall syndrome: clinical and molecular analysis. Clin Genet. 2000, 58: 28–30.

15.

Kim

Hui

. The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet. 2001, 59: 306–15.

16.

Kohlhase

Wischermann

Reichenbach

Froster

Engel

. Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Nat Genet. 1998, 18: 81–3.

17.

Lettice

Heaney

SJH

Purdie

et al.

A long range SHH enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet. 2003, 12: 1725–35.

18.

Marangoz

Leblebicioglu

. Thumb polydactyly with radius hypoplasia. A case report. J Hand Surg Am. 2006, 31: 1667–70.

19.

Minguella-Sola

Cabrera-Gonzalez

Escola-Teixido

. Radial club hand and contralateral pre-axial polydactyly. Report of 2 unusual cases. An Esp Pediatr. 1999, 51: 68–70.

20.

Norbnop

Srichomthong

Suphapeetiporn

Shotelersuk

. ZRS 406 A>G mutation patients with tibial hypoplasia, polydactyly and triphalangeal first fingers. J Hum Genet. 2014, 59: 467–70.

21.

Oberg

. Review of the molecular development of the thumb: digit primera. Clin Orthop Related Res. 2014, 472: 1101–5.

22.

Oberg

Feenstra

Manske

Tonkin

. Developmental biology and classification of congenital anomalies of the hand and upper extremity. J Hand Surg Am. 2010, 35: 2066–76.

23.

Philandrianos

Salazard

Casanova

. Two rare cases of associated of thumb hypoplasia and polydactyly of the homolateral foot. J Hand Surg Eur. 2009, 34: 125–7.

24.

Rotman

Manske

. Radial club hand and contralateral duplicated thumb. J Hand Surg Am. 1994, 19: 361–3.

25.

Solomon

. VACTERL/VATER Association. Orphanet J Rare Dis. 2011, 6: 56.

26.

Tabin

Wolpert

. Rethinking the proximodistal axis of the vertebrate limb in the molecular era. Genes Dev. 2007, 21: 1433–42.

27.

Vanlerberghe

Faivre

Petit

et al.

Intrafamilial variability of ZRS associated syndrome: characterization of a mosaic ZRS mutation by pyrosequencing. Clin Genet. 2015, 88: 479–83.

28.

Vander Meer

Lozano

Sun

et al.

A novel ZRS mutation leads to preaxial polydactyly type 2 in a heterozygous form and Werner mesomelic syndrome in a homozygous form. Hum Mutat. 2014, 35: 945–8.

29.

Verloes

Narcy

Fallet-Bianco

(1995) Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence, microphthalmia, pulmonary malformations, radial hypoplasia and müllerian regression: further delineation of a new syndrome? Clin Dysmorphol 4: 33–7.

30.

Wang

Gao

et al.

Leukemic survival factor SALL4 contributes to defective DNA damage repair. Oncogene. 2016, 35: 6087–95.

31.

Wieczorek

Pawlik

et al.

A specific mutation in the distant sonic hedgehog (SHH) cis-regulatory (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. Hum Mut. 2010, 31: 81–9.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.07 MB

0.05 MB