Indian J Pediatr DOI 10.1007/s12098-014-1569-2
SCIENTIFIC LETTER
Symmetrical Terminal Transverse Limb Deficiencies Divya Agarwal & Shalini S. Nayak & Prashanth K. Adiga & Shubha R. Phadke & Katta M. Girisha
Received: 6 June 2014 / Accepted: 19 August 2014 # Dr. K C Chaudhuri Foundation 2014
To the Editor: Two fetuses were evaluated following abortion (fetus 1) or intrauterine demise (fetus 2). In both cases, mothers were primigravidae with no antenatal history of teratogenic exposure. The family history was unremarkable and the couples were non-consanguineous. In fetus 1, antenatal sonography revealed all fetal parameters at 22 wk of gestation. However, hands were not visualized. On examination, the fetus had micrognathia (Fig. 1a and b). There was symmetrical absence of hands and digits with preservation of dorsoventral differentiation of skin at the limb terminus (Fig. 1a). Lower limbs were normal and internal examination was unremarkable. Radiograph of the hands revealed bilateral absence of metacarpals and phalanges (Fig. 1c). The anthropometric measurements of fetus 2 corresponded to 15 wk of gestation. Fetus had significant nuchal edema. Both hands were underdeveloped with absence of all fingers. Both feet were completely absent (Fig. 2a and b). There were no other external or internal anomalies. Radiographs showed normal long bones. Metacarpals and phalanges in both hands were small. Metatarsals and phalanges in both feet were completely absent (Fig. 2c and d). Unfortunately, due to non-availability of DNA, we were not able to perform any molecular studies.
We hereby report on two fetuses with symmetrical, bilateral and isolated terminal transverse limb reduction defects. These defects are rare anomalies referring to absence or hypoplasia of distal structures of limbs with normal proximal parts. In most cases it is difficult to ascertain a cause. Unilateral defects that occur more frequently are often thought to arise from disruptive forces like amniotic bands, thromboembolic phenomenon, vasospastic drug exposure and they are rarely familial [1, 2]. Bilateral, symmetrical and apparently non-syndromic transverse limb defects have been reported extremely rarely [3]. Saeed et al., identified 9 cases of isolated transverse limb defect [4]. The abnormality in these cases ranged in severity and in only one case there was bilateral involvement. To the best of our knowledge, there have been no reports similar to the pattern described here. The current understanding of genetic basis for limb development has essentially evolved from
D. Agarwal : S. R. Phadke Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India S. S. Nayak : K. M. Girisha (*) Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal 576104, India e-mail: [email protected] P. K. Adiga Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, India
Fig. 1 Clinical photographs of fetus 1 show micrognathia and bilateral absence of hands (a,b). Radiographs show absence of carpals, metacarpals and phalanges bilaterally with normal radius and ulna (c)
Indian J Pediatr
(AER) is removed [5]. Hence, genes involved in the AER and fibroblast growth factor (FGF) pathway or Hox-A and Hox-D clusters which control proximodistal patterning are likely candidates in these types of transverse limb deficiency. We postulate that they are likely to have a genetic or teratogenic basis in view of bilateral symmetrical involvement. Acknowledgments The authors are grateful to the families for consenting to participate in the study. Conflict of Interest None. Source of Funding The work was partially supported by the grant from Indian Council of Medical Research (BMS No. 54/5/2010).
References
Fig. 2 Bilateral underdeveloped hands with small fingers and absence of feet can be noted in fetus 2 (a, b). Hypoplastic bones of hands and complete absence of tarsals, metatarsals and phalanges in both feet can be appreciated (c, d)
various embryo studies and animal experiments. The phenotype of described cases is similar to that seen in animal experiments where apical ectodermal ridge
1. Werler MM, Bosco JL, Shapira SK, National Birth Defects Prevention Study. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects. Birth Defects Res A Clin Mol Teratol. 2009;85:52–7. 2. Graham Jr JM, Brown FE, Struckmeyer CL, Hallowell C. Dominantly inherited unilateral terminal transverse defects of the hand (adactylia) in twin sisters and one daughter. Pediatrics. 1986;78:103–6. 3. Horn D, Kolb GP. Two isolated cases with symmetrically absent hands and feet. Clin Dysmorphol. 1994;3:228–33. 4. Saeed F, Paramasivam G, Wiechec M, Kumar S. Fetal transverse limb defects: case series and literature review. J Clin Ultrasound. 2011;39: 454–7. 5. Niswander L. Pattern formation: old models out on a limb. Nat Rev Genet. 2003;4:133–43.
SCIENTIFIC LETTER
Symmetrical Terminal Transverse Limb Deficiencies Divya Agarwal & Shalini S. Nayak & Prashanth K. Adiga & Shubha R. Phadke & Katta M. Girisha
Received: 6 June 2014 / Accepted: 19 August 2014 # Dr. K C Chaudhuri Foundation 2014
To the Editor: Two fetuses were evaluated following abortion (fetus 1) or intrauterine demise (fetus 2). In both cases, mothers were primigravidae with no antenatal history of teratogenic exposure. The family history was unremarkable and the couples were non-consanguineous. In fetus 1, antenatal sonography revealed all fetal parameters at 22 wk of gestation. However, hands were not visualized. On examination, the fetus had micrognathia (Fig. 1a and b). There was symmetrical absence of hands and digits with preservation of dorsoventral differentiation of skin at the limb terminus (Fig. 1a). Lower limbs were normal and internal examination was unremarkable. Radiograph of the hands revealed bilateral absence of metacarpals and phalanges (Fig. 1c). The anthropometric measurements of fetus 2 corresponded to 15 wk of gestation. Fetus had significant nuchal edema. Both hands were underdeveloped with absence of all fingers. Both feet were completely absent (Fig. 2a and b). There were no other external or internal anomalies. Radiographs showed normal long bones. Metacarpals and phalanges in both hands were small. Metatarsals and phalanges in both feet were completely absent (Fig. 2c and d). Unfortunately, due to non-availability of DNA, we were not able to perform any molecular studies.
We hereby report on two fetuses with symmetrical, bilateral and isolated terminal transverse limb reduction defects. These defects are rare anomalies referring to absence or hypoplasia of distal structures of limbs with normal proximal parts. In most cases it is difficult to ascertain a cause. Unilateral defects that occur more frequently are often thought to arise from disruptive forces like amniotic bands, thromboembolic phenomenon, vasospastic drug exposure and they are rarely familial [1, 2]. Bilateral, symmetrical and apparently non-syndromic transverse limb defects have been reported extremely rarely [3]. Saeed et al., identified 9 cases of isolated transverse limb defect [4]. The abnormality in these cases ranged in severity and in only one case there was bilateral involvement. To the best of our knowledge, there have been no reports similar to the pattern described here. The current understanding of genetic basis for limb development has essentially evolved from
D. Agarwal : S. R. Phadke Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India S. S. Nayak : K. M. Girisha (*) Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal 576104, India e-mail: [email protected] P. K. Adiga Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, India
Fig. 1 Clinical photographs of fetus 1 show micrognathia and bilateral absence of hands (a,b). Radiographs show absence of carpals, metacarpals and phalanges bilaterally with normal radius and ulna (c)
Indian J Pediatr
(AER) is removed [5]. Hence, genes involved in the AER and fibroblast growth factor (FGF) pathway or Hox-A and Hox-D clusters which control proximodistal patterning are likely candidates in these types of transverse limb deficiency. We postulate that they are likely to have a genetic or teratogenic basis in view of bilateral symmetrical involvement. Acknowledgments The authors are grateful to the families for consenting to participate in the study. Conflict of Interest None. Source of Funding The work was partially supported by the grant from Indian Council of Medical Research (BMS No. 54/5/2010).
References
Fig. 2 Bilateral underdeveloped hands with small fingers and absence of feet can be noted in fetus 2 (a, b). Hypoplastic bones of hands and complete absence of tarsals, metatarsals and phalanges in both feet can be appreciated (c, d)
various embryo studies and animal experiments. The phenotype of described cases is similar to that seen in animal experiments where apical ectodermal ridge
1. Werler MM, Bosco JL, Shapira SK, National Birth Defects Prevention Study. Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects. Birth Defects Res A Clin Mol Teratol. 2009;85:52–7. 2. Graham Jr JM, Brown FE, Struckmeyer CL, Hallowell C. Dominantly inherited unilateral terminal transverse defects of the hand (adactylia) in twin sisters and one daughter. Pediatrics. 1986;78:103–6. 3. Horn D, Kolb GP. Two isolated cases with symmetrically absent hands and feet. Clin Dysmorphol. 1994;3:228–33. 4. Saeed F, Paramasivam G, Wiechec M, Kumar S. Fetal transverse limb defects: case series and literature review. J Clin Ultrasound. 2011;39: 454–7. 5. Niswander L. Pattern formation: old models out on a limb. Nat Rev Genet. 2003;4:133–43.
