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BRIEF REPORT
Year : 2014  |  Volume : 20  |  Issue : 1  |  Page : 92-95
 

Split-hand/feet malformation in three tamilian families and review of the reports from India


Department of Medicine, Jawaharlal Institute of Medical Education and Research, Pondicherry, India

Date of Web Publication19-May-2014

Correspondence Address:
S. Deepak Amalnath
Department of Medicine, Jawaharlal Institute of Medical Education and Research, Pondicherry 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-6866.132769

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   Abstract 

Split-hand/foot malformation (SHFM) is a rare condition which can be either syndromic or nonsyndromic. We report three unrelated pedigrees, one with autosomal dominant (AD) inheritance and the other two with autosomal recessive (AR) pattern. We also briefly review the published reports from India.


Keywords: Autosomal dominant, autosomal recessive, ectrodactyly, Indian, split-hand/foot malformation


How to cite this article:
Amalnath SD, Gopalakrishnan M, Dutta TK. Split-hand/feet malformation in three tamilian families and review of the reports from India. Indian J Hum Genet 2014;20:92-5

How to cite this URL:
Amalnath SD, Gopalakrishnan M, Dutta TK. Split-hand/feet malformation in three tamilian families and review of the reports from India. Indian J Hum Genet [serial online] 2014 [cited 2016 Aug 24];20:92-5. Available from: http://www.ijhg.com/text.asp?2014/20/1/92/132769



   Introduction Top


Split-hand/foot malformation (SHFM) also known as ectrodactyly or Lobster hand foot malformation, is defined as longitudinal deficiency of a digital ray of the hand or foot except the first or fifth digits [1] (Biesecker, 2009).

SHFM can be a part of a syndrome or can manifest as an isolated malformation. Nearly 50 syndromes have been described with SHFM, the most common being the ectrodactyly-ectodermal dysplasia-cleft syndrome (EEC). Nonsyndromic SHFM can be autosomal dominant (AD), recessive (AR), or X-linked recessive (XLR). [2] We report three unrelated families with nonsyndromic SHFM.


   Case Report Top


Pedigree 1

A 40-year-old man was admitted for poisoning. His son was incidentally noted to have SHFM. He was born of nonconsanguineous marriage. Similar deformities were present in his mother and brother [Figure 1]. This was present over four generations of the mother's family (seven more members) suggesting AD pattern of inheritance. None of the observed members had any features of ectodermal dyplasia. Despite the deformities, both the brothers were employed, while the mother could knit clothes in her free time.
Figure 1: Mother and two siblings with s plit-hand/foot malformation (SHFM)

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Pedigree 2

A 12-year-old girl who had come to visit a patient was found to have SHFM without any skin or teeth anomalies. Similar deformities were present in her sister [Figure 2], but not in the parents; suggestive of AR pattern.
Figure 2: Two sisters with SHFM

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Pedigree 3

A 19-year-old boy was on follow-up for diabetes. He had developmental delay with deaf mutism. He had SHFM of the left upper limb [Figure 3]. Skin and teeth were normal. He was born of consanguineous marriage and his father said that the boy's elder sibling died after birth and it had similar shaped hands and feet. The parents were normal suggesting AR inheritance.
Figure 3: SHFM in one limb

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   Discussion Top


The basis for SHFM is related to the defects in the patterning of the limb development. The three major tissues responsible for limb patterning are: Apical ectodermal ridge (AER), zone of polarizing activity (ZPA), and progress zone (PZ). The AER determines the proximodistal axis by directing the PZ. The ZPA determines the anteroposterior axis of the limb. [2]

Three mechanisms have been proposed for the limb defects in SHFM. Experimental evidence suggests a defect in the AER or ZPA. Second, involvement of late limb patterning genes like Ho × 13 could produce similar defects. A third explanation involves viewing the defect as a branching rather than a patterning defect. [2]

SHFM can be nonsyndromic or as a part of other syndromes like EEC. Nonsyndromic form can have associated long bone defects like tibial aplasia, known as SHFM with long bone deficiency (SHFLD).

The EEC syndrome is the most common form of syndromic SHFM, with cleft lip/palate and teeth and skin anomalies. Mutations in the p63 locus (SHFM 4) are often associated with EEC and SHFM.

So far six genetic loci have been described for SHFM [2] [Table 1]. These include AD (most common), AR (SHFM 6) and XLR inheritances (SHFM 2) have been described. Of these, only p63 [3] and Wnt10B [4] have been identified conclusively as the disease causing genes.
Table 1: Split - hand/foot malformation types and associated conditions with genes responsible


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Review of reports from India

We searched PubMed, Google, and IndMed with the keywords: SHFM, ectrodactyly, India, EEC syndrome. One report was not included due to the nonavailability of any details. A total of 30 prior published reports were included for analysis. Adding our 14 persons to the previously published 66 people, a total of 80 were analyzed [Table 2].
Table 2: Summary of the reported Indian cases


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Two-thirds of the 80 individuals were familial (AD 65% and AR 12%), with the rest being sporadic (23%). Maternal valproate use was implicated in one case.

The EEC syndrome was present in 50% of the patients with AD inheritance in 32 and sporadic occurrence in 10 patients. There were no AR cases with EEC syndrome.[34]

Of the 18 sporadic cases, EEC syndrome was present in 10, tibial aplasia in two, and fibular aplasia in one with only five having SHFM. Only one of the nine AD families had isolated SHFM; whereas, all the AR cases had isolated SHFM.

Overall, other associated anomalies included tibial aplasia (four), deafness (two), enlarged cistern magna (one), fibular aplasia (one), and nystagmus (Karsch-Neugebauer syndrome - one).


   Conclusion Top


This report highlights the varied presentation and inheritance of SHFM in India, with a significant number of reports with a negative family history. These patients may have recessive inheritance or new mutations. Further analysis of these persons could help in understanding this unique condition.

 
   References Top

1.Biesecker LG, Aase JM, Clericuzio C, Gurrieri F, Temple IK, Toriello H. Elements of morphology: Standard terminology for the hands and feet. Am J Med Genet Part A 2009;149A: 93-127.  Back to cited text no. 1
    
2.Duijf PH, van Bokhoven H, Brunner HG. Pathogenesis of split-hand/split-foot malformation. Hum Mol Genet 2003;12:R51-60.  Back to cited text no. 2
    
3.Celli J, Duijf P, Hamel BC, Bamshad M, Kramer B, Smits AP, et al. Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 1999;99:143-53.  Back to cited text no. 3
    
4.Khan S, Basit S, Zimri FK, Ali N, Ali G, Ansar M, et al. A novel homozygous missense mutation in WNT10B in familial split-hand/foot malformation. Clin Genet 2012;82:48-55.  Back to cited text no. 4
    
5.Joseph R, Nath SG. Association of generalized aggressive periodontitis and ectrodactyly-ectodermal dysplasia-cleft syndrome. Indian J Hum Genet 2012;18:259-62.  Back to cited text no. 5
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8.Singh D, Daniel R, Verma M, Akhter Z, Beri RS. Split hand/split foot syndrome with atresia of nasolacrimal ducts and buphthalmos. Indian Pediatr 1989;26:1053-5.  Back to cited text no. 8
    
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11.Choonia AS, Salgar NM. Syndromic form of autosomal dominant split foot malformation. Bombay Hosp J 2011;53.  Back to cited text no. 11
    
12.Shenoy R, Kamath N. Bilateral congenital split hand with tibial aplasia. Indian J Pediatr 2004;71:948.  Back to cited text no. 12
    
13.Sharma S, Chhetri A, Singh A. Congenital cleft foot and hand. Indian Pediatr 1999;36:935-8.  Back to cited text no. 13
    
14.Jindal G, Parmar VR, Gupta VK. Ectrodactyly/split hand feet malformation. Indian J Hum Genet 20009;15:140-2.  Back to cited text no. 14
    
15.Verma IC, Joseph R, Bhargava S, Mehta S. Split-hand and split-foot deformity inherited as an autosomal recessive trait. Clin Genet 1976;9:8-14.  Back to cited text no. 15
    
16.Smith R. Available from: http://fovuk.tripod.com/home.html [Last accessed o n 2013 Apr 05].  Back to cited text no. 16
    
17.Malvankar DD, Sacchidanand S, Mallikarjun M. Ectrodactyly, ectodermal dysplasia, and cleft lip-palate (EEC) syndrome without clefting: A rare case report. Dermatol Online J 2012;18:5.  Back to cited text no. 17
    
18.Shivaprakash PK, Joshi HV, Noorani H, Reddy V. Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome: A case report of "Incomplete syndrome". Contemp Clin Dent 2012;3:S115-7.  Back to cited text no. 18
    
19.Marwaha M, Nanda KD. Ectrodactyly, ectodermal dysplasia, cleft lip, and palate (EEC syndrome). Contemp Clin Dent 2012;3:205-8.  Back to cited text no. 19
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24.Parkash H, Grewal MS, Sidhu SS. Ectrodactyly, ectodermal dysplasia, cleft lip and palate (EEC): A rare syndrome. Indian J Pediatr 1983;50:337-40.  Back to cited text no. 24
    
25.Thapa R, Mallick D, Biswas B, Ghosh A. Mega cisterna magna in ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome. Indian J Pediatr 2010;77:706.  Back to cited text no. 25
    
26.Mathian VM, Sundaram AM, Karunakaran R, Vijayaragavan R, Vinod S, Rubini R. An unusual occurrence of Karsch-Neugebauer syndrome with orodental anomalies. J Pharm Bioallied Sci 2012;4:S171-3.  Back to cited text no. 26
    
27.Sarkar S. Orodental abnormalities in lobster claw syndrome (a type of syndactyly). J Indian Soc Pedod Prev Dent 1999;17:107-10.  Back to cited text no. 27
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28.Lodha A, Mody P, Malik A, Singh S. Ectrodactyly fibular aplasia. Indian Pediatr 1993;30:1123-5.  Back to cited text no. 28
    
29.Thami GP, Kaur S. Split hand-foot malformation: A congenital central limb ray deficiency. J Postgrad Med 2002;48:209-10.  Back to cited text no. 29
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30.Kalla G, Garg A. Ectrodactyly. Indian J Dermatol Venereol Leprol 2002;68:152-3.  Back to cited text no. 30
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32.Managoli SS, Chaturvedi P. Tibial hemimelia-split hand/foot syndrome with rare anomalies. Indian Pediatr 2005;42:190-1.  Back to cited text no. 32
    
33.Riyaz N, Riyaz A, Chandran R, Rakesh SV. Focal dermal hypoplasia (Goltz syndrome). Indian J Dermatol Venereol Leprol 2005;71:279-81.  Back to cited text no. 33
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34.Sukumaran S, Krishnamoorthy T, Thomas SV. Split-hand/split-foot malformation associated with maternal valproate consumption. Neurol India 2005;53:251-2.  Back to cited text no. 34
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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