253
Journal of Neonatal-Perinatal Medicine 7 (2014) 253–256 DOI 10.3233/NPM-1476813 IOS Press
Case report
A rare association: Sirenomelia with adrenalomegaly in an infant of diabetic mother M.A. Ozturka , O. Bastuga,∗ , H. Halisa , L. Korkmaza , S. Memura , D. Saricia and A. Karab a Erciyes b Erciyes
University Medical Faculty, Department of Neonatology, Kayseri, Turkey University Medical Faculty, Department of Pediatrics, Kayseri, Turkey
Received 5 December 2013 Revised 5 March 2014 Accepted 25 March 2014
Abstract. Sirenomelia or the Mermaid syndrome is a rare congenital anomaly with an incidence of one in 60,000 to 70,000 pregnancies. Sirenomelia is characterized by complete fusion of the lower limbs, commonly associated with renal agenesis, absent external genitalia and other gastrointestinal defects. A 37-week, 3040-g infant was born to a 35-year-old multigravida mother with type 2 diabetes mellitus and hyperlipidemia. To our knowledge, this is the first case of sirenomelia with adrenalomegaly. Keywords: Sirenomelia, adrenalomegaly, infant, diabetes, Mermaid syndrome
1. Introduction Infants of diabetic mothers have two to five times the incidence of congenital malformations than that in other infants. These anomalies include defects of the neural tube, heart, urogenital system, skeleton and alimentary tract, and the caudal regression syndrome. The anomalies are considered to result from the maternal metabolic derangements [1, 2]. Sirenomelia, alternatively known as ‘mermaid syndrome’ is a rare congenital anomaly of caudal region of the body with an incidence of 0.98 in 100.000 births worldwide [3]. This deformity is defined as a polymalformative syndrome that associates muscular, skeleton, and visceral abnormalities [4, 5]. Sirenomelia is characterized by complete fusion of the ∗ Corresponding
author: Dr. Osman Bastug, Division of Neonatology, Department of Pediatrics, Erciyes University Medical Faculty, Talas Street, 38039 Kayseri, Turkey. Tel.: +90 3522076666; Fax: +90 3524375825; E-mail: [email protected].
lower limbs, commonly associated with renal agenesis, absent external genitalia and other gastrointestinal defects [6]. The incidence is increased in monozygotic twins [7]. Etiology is unknown with a male preponderance and the pathogenic mechanisms of these defects are still discussed [8, 9]. The association of diabetic embryopathy with adrenalomegaly (adrenal enlargement) and sirenomelia has never been reported in medical literature, based on online medical searching. This is the first report of associated sirenomelia and adrenalomegaly in a case of diabetic fetopathy.
2. Case report A 37-week, 3040-g (46 cm height and 35 cm head circumference) infant was born to a 35-year-old multigravida mother with type 2 diabetes mellitus and
1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
254
M.A. Ozturk et al. / Sirenomelia with adrenalomegaly
a
b
c
Fig. 2. Bilateral adrenal hyperplasia. Fig. 1. a: Complete fusion of the lower limbs, b: A small soft tissue projection at the tip of the coccyx suggestive or vestigeal tail, c: Absence of the external genitalia and bilateral pes equniovarus.
hyperlipidemia. The parents were unrelated. Her antenatal period was uneventful and there was no history of any drug intake. There was neither a past nor a family history of malformations. His mother was diagnosed with type 2 diabetes mellitus at age 32 years. Throughout pregnancy, follow-up were poorly controlled. HbA1c levels were not controlled before and during pregnancy. Prenatal ultrasound showed ambigus genitale, cardiac pathology and shortness of lower extremity so mother was referred to our hospital. The infant was born with Apgar scores of 1/3. Physical examination of the infant showed complete fusion of the lower limbs with bilateral pes equniovarus, absence of the external genitalia, urogenital and anal orifices, a single umbilical artery and a small soft tissue projection at the tip of the coccyx suggestive or vestigeal tail. The caudal appendage was 4 cm long 2 cm in diameter and had soft fibrous consistency (Fig. 1 a–c).
Echocardiography revealed double outlet right ventricule, hypoplasia of aortic arc, atrial septal defect, and patent ductus arteriosus. Ultrasonography and Magnetic resonance imaging revealed hypoplastic and horseshoe kidneys and bilateral adrenal enlargement [the left adrenal gland length and thickness 31 × 5 mm, the right adrenal gland 29 × 7 mm (normal range; 17.3 ± 1.8)] (Fig. 2) [10]. The case was accepted as exitus at the twenty four hour of life despite all interventions. Autopsy to the patient was not performed. 3. Discussion In 1961, Duhamel first described the spectrum of CRS (the syndrome of caudal regression) as a spectrum of congenital malformations, which consist of anomalies of the rectum, the urinary and genital systems, the lumbosacral spine, and the lower limbs. The most severe end of the spectrum is the fusion of the lower limbs and the major organ malformations. This is known as sirenomelia or mermaid syndrome [11].
M.A. Ozturk et al. / Sirenomelia with adrenalomegaly
Controversy exists in the literature regarding whether sirenomelia occurs as a separate entity or the extreme form of CRS. Twickler et al. reported the differences between these two conditions after examining four cases of sirenomelia and three cases of CRS. They are the presence of single aberrant umbilical arteries, lethal renal anomalies (agenesis or dysgenesis), single or fused extremities, absent anus, and reduced amniotic fluid sirenomelia from CRS. In addition, CRS is strongly associated with maternal diabetes [12]. Animal experiments have shown that CRS- like syndrome could be induced by agents including retinoic acid, diethylpropion, lithium, sulfamide, cadmium, lead, ochratoxin A, vitamin A deficiency, radiation, hyperthermia, organic fat solvents, and 6- aminonicotinamide. Familial transmission of CRS has been reported, but Mendelian pattern of inheritance has not been shown [13]. A recent study provides evidence for involvement of the homeobox gene, HLXB9, in dominantly inherited sacral agenesis, but a possible role for this gene in the development of caudal dysgenesis has not been established [14]. Sirenomelia is fatal because of bilateral renal agenesis and associated severe pulmonary hypoplasia. There is currently no known serum marker that may be used for antenatal diagnosis of sirenomelia. Prenatal ultrasonography is used to diagnose sirenomelia [15, 16]. There are the needs of close monitoring diabetic women in the fertile age in order to prevent the increased rate of specific malformations. It is possible to demonstrate sirenomelia as early as 20 weeks of pregnancy and it being a complex and lethal malformation, an early diagnosis could be useful in terminating the pregnancy. Adrenomegaly is defined as enlargement of the adrenal glands. Our literature search concerning the incidence of neonatal adrenomegaly did not find any publication. Furthermore, in the literature, adrenomegaly or adrenal cytomegaly in newborn infants is described most often in Beckwith–Wiedemann syndrome. Adrenomegaly or adrenal cytomegaly in sirenomelia has not been described. However, adrenomegaly may be a coincidental association with sirenomelia. Poorly controlled diabetes mellitus can be a risk factor for sirenomelia [17]. Although, the association with diabetic embryopathy and bilateral adrenal hyperplasia has been reported previously [18], sirenomelia and adrenalomegaly (or adrenal enlargement) togetherness has not been shown in infants of diabetic mothers.
255
We present association with sirenomelia and adrenalomegaly (adrenal enlargement) in an infant of diabetic mother. To our knowledge, this association has not been reported previously.
Financial disclosure statement The authors declare no conflict of interest.
References [1]
[2] [3]
[4]
[5]
[6] [7] [8]
[9]
[10]
[11]
[12]
[13]
Cousins L. Etiology and prevention of congenital anomalies among infants of overt diabetic women. Clin Obstet Gynecol 1991;34:481-93. Reece EA, Homko CJ. Infant of Diabetic Mother. Semin Perinatol 1994;18:459-69. Orioli IM, Amar E, Arteaga-Vazquez J, Bakker MK, Bianca S, Botto LD, Clementi M, Correa A, Csaky-Szunyogh M, Leoncini E, Li Z, L´opez-Camelo JS, Lowry RB, Marengo L, Mart´inez-Fr´ias ML, Mastroiacovo P, Morgan M, Pierini A, Ritvanen A, Scarano G, Szabova E, Castilla EE. Sirenomelia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review. Am J Med Genet C Semin Med Genet 2011:15;157C:358-73. Goodlow OG, Sibley RI, Allen BG, Kamanda WS, Gullattee AC, Rayfield WC. Sirenomelia: Mermaid syndrome. J Natl Med Assoc 1988;80:343-6. Lhuaire M, Jestin A, Boulagnon C, Loock M, Doco-Fenzy M, Gaillard D, Diebold MD, Avisse C, Labrousse M. Sirenomelia: A new type, showing VACTERL association with Thomas syndrome and a review of literature. Birth Defects Res A Clin Mol Teratol 2013;97:123-32. Mandal S, Bandyopadhyay A, Ray S. Sirenomelia: A case report. J Indian Med Assoc 2009;107:43-4. Duncan PA, Shapiro LR, Klein RM. Sacrococcygeal dysgenesis association. Am J Med Genet 1991;41:153-61. Nievelstein RA, Valk J, Smith LM, Vermeij-Keers C. MR of the caudal regression syndrome: Embryologic implications. AJNR Am J Neuroradiol 1994;15:1021-9. Fukada Y, Yasumizu T, Tsurugi Y, Ohta S, Hoshi K. Caudal regression syndrome detected in a fetus with increased nuchal translucency. Acta Obstet Gynecol Scand 1999;78: 655-6. Scott EM, Thomas A, McGarrigle HH, Lachelin GC. Serial adrenal ultrasonography in normal neonates. J Ultrasound Med 1990;9:279-283. Duhamel B. From the mermaid to anal imperforation: The syndrome of caudal regression. Arch Dis Child 1961;36: 152-5. Twickler D, Budorick N, Pretorius D, Grafe M, Currarino G. Caudal regression versus sirenomelia: Sonographic clues. J Ultrasound Med 1993;12:323-30. Begum S, Shelim R, Begum T, Nahar N. Caudal Regression Syndrome - A Case Report and Literature Review. J Bangladesh Coll Phys Surg 2011;29:166-69.
256
[14]
[15]
M.A. Ozturk et al. / Sirenomelia with adrenalomegaly
Ross AJ, Ruiz-Perez V, Wang Y, Hagan DM, Scherer S, Lynch SA, Lindsay S, Custard E, Belloni E, Wilson DI, Wadey R, Goodman F, Orstavik KH, Monclair T, Robson S, Reardon W, Burn J, Scambler P, Strachan T. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet 1998;20:358-61. Adra A, Cordero D, Mejides A, Yasin S, Salman F, O’Sullivan MJ. Caudal regression syndrome: Etiopathogenesis, prenatal diagnosis and perinatal management. Obstet Gynecol Surv 1994;49:508-16.
[16] [17]
[18]
Sirtori M, Ghidini A, Romero R, Obbins JC. Prenatal diagnosis of sirenomelia. J Ultrasound Med 1989;8:83-8. Morfeld CA, Hofstaetter C, Adolf S, Radner H, Schild RL. [Sirenomelia–a rare cause of an oligoanhydramnion in the second trimester–a case report]. Z Geburtshilfe Neonatol 2012;216:34-6. Tantbirojn P, Taweevisit M, Sritippayawan S, Uerpairojkit B. Diabetic fetopathy associated with bilateral adrenal hyperplasia and ambiguous genitalia: A case report. J Med Case Rep 2008;2:251.
Copyright of Journal of Neonatal -- Perinatal Medicine is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Journal of Neonatal-Perinatal Medicine 7 (2014) 253–256 DOI 10.3233/NPM-1476813 IOS Press
Case report
A rare association: Sirenomelia with adrenalomegaly in an infant of diabetic mother M.A. Ozturka , O. Bastuga,∗ , H. Halisa , L. Korkmaza , S. Memura , D. Saricia and A. Karab a Erciyes b Erciyes
University Medical Faculty, Department of Neonatology, Kayseri, Turkey University Medical Faculty, Department of Pediatrics, Kayseri, Turkey
Received 5 December 2013 Revised 5 March 2014 Accepted 25 March 2014
Abstract. Sirenomelia or the Mermaid syndrome is a rare congenital anomaly with an incidence of one in 60,000 to 70,000 pregnancies. Sirenomelia is characterized by complete fusion of the lower limbs, commonly associated with renal agenesis, absent external genitalia and other gastrointestinal defects. A 37-week, 3040-g infant was born to a 35-year-old multigravida mother with type 2 diabetes mellitus and hyperlipidemia. To our knowledge, this is the first case of sirenomelia with adrenalomegaly. Keywords: Sirenomelia, adrenalomegaly, infant, diabetes, Mermaid syndrome
1. Introduction Infants of diabetic mothers have two to five times the incidence of congenital malformations than that in other infants. These anomalies include defects of the neural tube, heart, urogenital system, skeleton and alimentary tract, and the caudal regression syndrome. The anomalies are considered to result from the maternal metabolic derangements [1, 2]. Sirenomelia, alternatively known as ‘mermaid syndrome’ is a rare congenital anomaly of caudal region of the body with an incidence of 0.98 in 100.000 births worldwide [3]. This deformity is defined as a polymalformative syndrome that associates muscular, skeleton, and visceral abnormalities [4, 5]. Sirenomelia is characterized by complete fusion of the ∗ Corresponding
author: Dr. Osman Bastug, Division of Neonatology, Department of Pediatrics, Erciyes University Medical Faculty, Talas Street, 38039 Kayseri, Turkey. Tel.: +90 3522076666; Fax: +90 3524375825; E-mail: [email protected].
lower limbs, commonly associated with renal agenesis, absent external genitalia and other gastrointestinal defects [6]. The incidence is increased in monozygotic twins [7]. Etiology is unknown with a male preponderance and the pathogenic mechanisms of these defects are still discussed [8, 9]. The association of diabetic embryopathy with adrenalomegaly (adrenal enlargement) and sirenomelia has never been reported in medical literature, based on online medical searching. This is the first report of associated sirenomelia and adrenalomegaly in a case of diabetic fetopathy.
2. Case report A 37-week, 3040-g (46 cm height and 35 cm head circumference) infant was born to a 35-year-old multigravida mother with type 2 diabetes mellitus and
1934-5798/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved
254
M.A. Ozturk et al. / Sirenomelia with adrenalomegaly
a
b
c
Fig. 2. Bilateral adrenal hyperplasia. Fig. 1. a: Complete fusion of the lower limbs, b: A small soft tissue projection at the tip of the coccyx suggestive or vestigeal tail, c: Absence of the external genitalia and bilateral pes equniovarus.
hyperlipidemia. The parents were unrelated. Her antenatal period was uneventful and there was no history of any drug intake. There was neither a past nor a family history of malformations. His mother was diagnosed with type 2 diabetes mellitus at age 32 years. Throughout pregnancy, follow-up were poorly controlled. HbA1c levels were not controlled before and during pregnancy. Prenatal ultrasound showed ambigus genitale, cardiac pathology and shortness of lower extremity so mother was referred to our hospital. The infant was born with Apgar scores of 1/3. Physical examination of the infant showed complete fusion of the lower limbs with bilateral pes equniovarus, absence of the external genitalia, urogenital and anal orifices, a single umbilical artery and a small soft tissue projection at the tip of the coccyx suggestive or vestigeal tail. The caudal appendage was 4 cm long 2 cm in diameter and had soft fibrous consistency (Fig. 1 a–c).
Echocardiography revealed double outlet right ventricule, hypoplasia of aortic arc, atrial septal defect, and patent ductus arteriosus. Ultrasonography and Magnetic resonance imaging revealed hypoplastic and horseshoe kidneys and bilateral adrenal enlargement [the left adrenal gland length and thickness 31 × 5 mm, the right adrenal gland 29 × 7 mm (normal range; 17.3 ± 1.8)] (Fig. 2) [10]. The case was accepted as exitus at the twenty four hour of life despite all interventions. Autopsy to the patient was not performed. 3. Discussion In 1961, Duhamel first described the spectrum of CRS (the syndrome of caudal regression) as a spectrum of congenital malformations, which consist of anomalies of the rectum, the urinary and genital systems, the lumbosacral spine, and the lower limbs. The most severe end of the spectrum is the fusion of the lower limbs and the major organ malformations. This is known as sirenomelia or mermaid syndrome [11].
M.A. Ozturk et al. / Sirenomelia with adrenalomegaly
Controversy exists in the literature regarding whether sirenomelia occurs as a separate entity or the extreme form of CRS. Twickler et al. reported the differences between these two conditions after examining four cases of sirenomelia and three cases of CRS. They are the presence of single aberrant umbilical arteries, lethal renal anomalies (agenesis or dysgenesis), single or fused extremities, absent anus, and reduced amniotic fluid sirenomelia from CRS. In addition, CRS is strongly associated with maternal diabetes [12]. Animal experiments have shown that CRS- like syndrome could be induced by agents including retinoic acid, diethylpropion, lithium, sulfamide, cadmium, lead, ochratoxin A, vitamin A deficiency, radiation, hyperthermia, organic fat solvents, and 6- aminonicotinamide. Familial transmission of CRS has been reported, but Mendelian pattern of inheritance has not been shown [13]. A recent study provides evidence for involvement of the homeobox gene, HLXB9, in dominantly inherited sacral agenesis, but a possible role for this gene in the development of caudal dysgenesis has not been established [14]. Sirenomelia is fatal because of bilateral renal agenesis and associated severe pulmonary hypoplasia. There is currently no known serum marker that may be used for antenatal diagnosis of sirenomelia. Prenatal ultrasonography is used to diagnose sirenomelia [15, 16]. There are the needs of close monitoring diabetic women in the fertile age in order to prevent the increased rate of specific malformations. It is possible to demonstrate sirenomelia as early as 20 weeks of pregnancy and it being a complex and lethal malformation, an early diagnosis could be useful in terminating the pregnancy. Adrenomegaly is defined as enlargement of the adrenal glands. Our literature search concerning the incidence of neonatal adrenomegaly did not find any publication. Furthermore, in the literature, adrenomegaly or adrenal cytomegaly in newborn infants is described most often in Beckwith–Wiedemann syndrome. Adrenomegaly or adrenal cytomegaly in sirenomelia has not been described. However, adrenomegaly may be a coincidental association with sirenomelia. Poorly controlled diabetes mellitus can be a risk factor for sirenomelia [17]. Although, the association with diabetic embryopathy and bilateral adrenal hyperplasia has been reported previously [18], sirenomelia and adrenalomegaly (or adrenal enlargement) togetherness has not been shown in infants of diabetic mothers.
255
We present association with sirenomelia and adrenalomegaly (adrenal enlargement) in an infant of diabetic mother. To our knowledge, this association has not been reported previously.
Financial disclosure statement The authors declare no conflict of interest.
References [1]
[2] [3]
[4]
[5]
[6] [7] [8]
[9]
[10]
[11]
[12]
[13]
Cousins L. Etiology and prevention of congenital anomalies among infants of overt diabetic women. Clin Obstet Gynecol 1991;34:481-93. Reece EA, Homko CJ. Infant of Diabetic Mother. Semin Perinatol 1994;18:459-69. Orioli IM, Amar E, Arteaga-Vazquez J, Bakker MK, Bianca S, Botto LD, Clementi M, Correa A, Csaky-Szunyogh M, Leoncini E, Li Z, L´opez-Camelo JS, Lowry RB, Marengo L, Mart´inez-Fr´ias ML, Mastroiacovo P, Morgan M, Pierini A, Ritvanen A, Scarano G, Szabova E, Castilla EE. Sirenomelia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review. Am J Med Genet C Semin Med Genet 2011:15;157C:358-73. Goodlow OG, Sibley RI, Allen BG, Kamanda WS, Gullattee AC, Rayfield WC. Sirenomelia: Mermaid syndrome. J Natl Med Assoc 1988;80:343-6. Lhuaire M, Jestin A, Boulagnon C, Loock M, Doco-Fenzy M, Gaillard D, Diebold MD, Avisse C, Labrousse M. Sirenomelia: A new type, showing VACTERL association with Thomas syndrome and a review of literature. Birth Defects Res A Clin Mol Teratol 2013;97:123-32. Mandal S, Bandyopadhyay A, Ray S. Sirenomelia: A case report. J Indian Med Assoc 2009;107:43-4. Duncan PA, Shapiro LR, Klein RM. Sacrococcygeal dysgenesis association. Am J Med Genet 1991;41:153-61. Nievelstein RA, Valk J, Smith LM, Vermeij-Keers C. MR of the caudal regression syndrome: Embryologic implications. AJNR Am J Neuroradiol 1994;15:1021-9. Fukada Y, Yasumizu T, Tsurugi Y, Ohta S, Hoshi K. Caudal regression syndrome detected in a fetus with increased nuchal translucency. Acta Obstet Gynecol Scand 1999;78: 655-6. Scott EM, Thomas A, McGarrigle HH, Lachelin GC. Serial adrenal ultrasonography in normal neonates. J Ultrasound Med 1990;9:279-283. Duhamel B. From the mermaid to anal imperforation: The syndrome of caudal regression. Arch Dis Child 1961;36: 152-5. Twickler D, Budorick N, Pretorius D, Grafe M, Currarino G. Caudal regression versus sirenomelia: Sonographic clues. J Ultrasound Med 1993;12:323-30. Begum S, Shelim R, Begum T, Nahar N. Caudal Regression Syndrome - A Case Report and Literature Review. J Bangladesh Coll Phys Surg 2011;29:166-69.
256
[14]
[15]
M.A. Ozturk et al. / Sirenomelia with adrenalomegaly
Ross AJ, Ruiz-Perez V, Wang Y, Hagan DM, Scherer S, Lynch SA, Lindsay S, Custard E, Belloni E, Wilson DI, Wadey R, Goodman F, Orstavik KH, Monclair T, Robson S, Reardon W, Burn J, Scambler P, Strachan T. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet 1998;20:358-61. Adra A, Cordero D, Mejides A, Yasin S, Salman F, O’Sullivan MJ. Caudal regression syndrome: Etiopathogenesis, prenatal diagnosis and perinatal management. Obstet Gynecol Surv 1994;49:508-16.
[16] [17]
[18]
Sirtori M, Ghidini A, Romero R, Obbins JC. Prenatal diagnosis of sirenomelia. J Ultrasound Med 1989;8:83-8. Morfeld CA, Hofstaetter C, Adolf S, Radner H, Schild RL. [Sirenomelia–a rare cause of an oligoanhydramnion in the second trimester–a case report]. Z Geburtshilfe Neonatol 2012;216:34-6. Tantbirojn P, Taweevisit M, Sritippayawan S, Uerpairojkit B. Diabetic fetopathy associated with bilateral adrenal hyperplasia and ambiguous genitalia: A case report. J Med Case Rep 2008;2:251.
Copyright of Journal of Neonatal -- Perinatal Medicine is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
