251Neurology India | June 2005 | Vol 53 | Issue 2

tions or consanguinity.

Split-hand/split-foot malformation (SHFM) is a limb mal-

formation involving the central rays of the autopod, present-

ing with syndactyly, median clefts in hand or foot and aplasia

or hypoplasia of metacarpals or metatarsals. Failure to main-

tain median apical ectodermal ridge (AER) signaling is the

main pathogenic mechanism for which genetic causes are im-

plicated. Five loci for SHFM have been mapped: SHFM1 on

chromosome 7q21, SHFM2 on chromosome Xq26, SHFM3

on chromosome 10q24, SHFM4 that is caused by mutation

in the TP63 gene on chromosome 3q27, and SHFM5 on 2q31.

SHFM may occur as an isolated entity or as part of a syn-

drome. Scherer et al. in 1994[1] have classified ectrodactyly in

to nine types after reviewing the published literature on clini-

cal and genetic data. Both dominant and recessive pattern of

inheritance have been documented in SHFM.

Our proband had no family history on pedigree evaluation

for three generations and he was born of a nonconsanguineous

parentage. In the reported case, prenatal exposure to valproate

appears to be the only risk factor involved, but a chance asso-

ciation cannot be excluded.

Several limb reduction deformities have been reported with

the use of valproic acid in clinical[2]–[7] and experimental set-

tings.[8] But split-hand malformation deformity in relation to

valproate exposure has not been reported earlier.

Sajith Sukumaran, Thamburaj Krishnamoorthy,S. V. Thomas

Kerala Registry of Epilepsy and Pregnancy, Department of Neurol-ogy, Sree Chitra Tirunal Institute for Medical Sciences and Technol-

ogy, Trivandrum, India. E-mail: sanjeev@sctimst.ker.nic.in

References

1. Scherer SW, Poorkaj P, Massa H, Soder S, Allen T, Nunes M, et al. Physical

mapping of the split hand/split foot locus on chromosome 7 and implication in

elinating in nature;[2],[3] however, our patient had milder dis-

ease and the GBS was of axonal type. Thus, dengue virus

infection too does not seem to result in any specific pattern of

GBS. However, all the reported cases survived and recovered

with appropriate therapy.

In conclusion, in patients presenting with GBS in whom

no usual antecedent infections are identified, screening for

dengue virus infection may help in identifying a rare cause.

Sudhir Kumar, Subhashini PrabhakarDivision of Neurology, Department of Neurological Sciences, Apollo

Hospitals, Jubilee Hills, Hyderabad, India. E-mail:drsudhirkumar@yahoo.com

References

1. Hughes RA, Hadden RD, Gregson NA, Smith KJ. Pathogenesis of Guillain-

Barre syndrome. J Neuroimmunol 1999;100:74-97.

2. Santos NQ, Azoubel AC, Lopes AA, Costa G, Bacellar A. Guillain-Barre syn-

drome in the course of dengue: Case report. Arq Neuropsiquiatr 2004;62:144-

6.

3. Esack A, Teelucksingh S, Singh N. The Guillain-Barre syndrome following

dengue fever. West Indian Med J 1999;48:36-7.

Accepted on 13-11-2004

Split-hand/split-footmalformation associated withmaternal valproateconsumption

Sir,

We examined a 3.5-year-old boy with congenital malforma-

tion of both upper limbs. His mother was taking sodium

valproate 800 mg daily for complex partial seizures through-

out pregnancy. There was no history of antenatal infection or

exposure to any other medications, alcohol, smoking, or expo-

sure to X-rays.

Both hands of the boy were malformed [Figure 1]. Below

the wrist, his palms were split into two parts, the distal end of

which had two fingers on the left and three fingers on the

right side. The fingers and parts of the palms could be moved

volitionally. He had mild hypertelorism and mild equinovarus

deformity of the right foot. Rest of the examination was nor-

mal.

X-rays [Figure 1] showed agenesis of two metacarpal bones

on the right side and three on the left side with phalanges

attached to them, resulting in a characteristic split-hand mal-

formation. There was only one carpal bone on the left side

and none on the right side. A detailed pedigree evaluation for

three generations failed to reveal any congenital malforma-

Figure 1: Photograph and X-ray of the hands. X-ray shows agenesis of twometacarpal bones on the right side and three on the left side with phalanges

attached to them, resulting in a characteristic split hand malformation

Letter to Editor

252 Neurology India | June 2005 | Vol 53 | Issue 2

syndromic ectrodactyly. Hum Mol Genet 1994;3:1345-54.

2. Kozma. C. Valproic acid embryopathy: Report of two siblings with further ex-

pansion of the phenotypic abnormalities and a review of the literature. Am J

Med Genet 2001;98:168-75.

3. Rodriguez-Pinilla E, Arroyo I, Fondevilla J, Garcia MJ, Martinez-Frias ML.

Prenatal exposure to valproic acid during pregnancy and limb deficiencies: A

case-control study. Am J Med Genet 2000;90:376-81.

4. Okada T, Tomoda T, Hisakawa H, Kurashige T. Fetal valproate syndrome with

reduction deformity of limb. Acta Paediatr Jpn 1995;37:58-60.

5. Sharony R, Garber A, Viskochil D, Schreck R, Platt LD, Ward R, et al. Preaxial

ray reduction defects as part of valproic acid embryofetopathy. Prenat Diagn

1993;13:909-18.

6. Pandya NA, Jani BR. Post-axial limb defects with maternal sodium valproate

exposure. Clin Dysmorphol 2000;9:143-4.

7. Verloes A, Frikiche A, Gremillet C, Paquay T, Decortis T, Rigo J, et al. Proxi-

mal phocomelia and radial ray aplasia in fetal valproic syndrome. Eur J Pediatr

1990;149:266-7.

8. Whitsel AI, Johnson CB, Forehand CJ. An in ovo chicken model to study the

systemic and localized teratogenic effects of valproic acid. Teratology

2002;66:153-63.

Accepted on 08-9-2004

Letter to Editor