Sonographic Findings in a Fetus with Congenital N ephrotic Syndrome of the Finnish Type Brian 5. Moore, MO,• Dolores H. Pretorius, MD,• Angela L. Scioscia, MD,t Vivian M. Reznik, MD+
CASE REPORT The affected pregnancy was the first of a nonconsanguineous Caucasian couple of English descent. The parents were each 27 years of age, had had no prior pregnancies, were in good health, and had no significant medical illness. The early pregnancy was uncomplicated. A maternal serum alpha· fetoprotein (MSAFP) sample was obtained at 16 weeks of gestation with dating based on a 6-week sonographic examination. The MSAFP value returned at 9.4 multiples of the median (MoM). A sonogram obtained at 17.3 weeks of gestation revealed biometry consistent with dating, normal amniotic fluid volume, normal intracranial anatomy, and normal spine, ventral wall, and bladder. The kidneys appeared slightly echogenic but were normal in size using tables developed by Lawson and coworkers 1 (Fig. 1). The MSAFP evaluation repeated at 17.8 weeks, was 9.3 MoM. The family was counseled regarding the significant risks of such an elevated MSAFP level as well as the limitations of ultrasound examination. At 18.3 weeks, a repeat sonogram was obtained and showed appropriate interval growth. The kidneys on this examination were of normal size and echogenicity and no anatomic abnormalities were detected. An amniocentesis was performed, which revealed a karyotype of 46,XY. The AFP concentration in the fluid was 46.4 mg per di, or 43.8 MoM; the acetylcholinesterase was negative. The family was in· formed of the risk of congenital nephrotic syndrome and of the possibility of an undetected anatomic abnormality. Be· cause of high likelihood of congenital nephrotic syndrome, Received April 17, 1991, from the Departments of• Radiology,
t Medicine and Reproductive Medicine, and t Pediatrics, University
of California, San Diego, California. Revised manuscript accepted for publication August 21. 1991. Address correspondence and reprint requests to Dolores Pretorius: UCSD Medical Center, Division of Diagnostic Ultrasound (8759), 225 Dickinson Street, San Diego, CA 92103-8759.
prenatal con&ultation with a pediatric nephrologist was ar· ranged for the family. A follow-up sonogram at 25 weeks of gestation demonstrated normal renal echogenicity but for the first time showed bila teral renal enlargement, both kidneys measuring 36 mm (Fig. 2). The remainder of the study, including am· niotic fluid volume, continued to be nonnal. Examinations at 26 and 30 weeks showed progressive renal enlargement, with both kidneys measuring 43 mm in length on the later study. The placenta, equivocally thick on earlier studies, measured 42 mm on the 30-week examination, greater than two standard deviations above the mean established by Haddick and colleagues. 2 A 1450 gram boy was born at 33 weeks of gestation after premature labor with fetal distress. Apgar scores were 5 and 7 at 1 and 5 minutes, respectively. Meconium staining was present at delivery, and the baby required a brief period of intubation for respiratory distress. Physical examination revealed large, firm kidneys. Massive proteinuria was present from birth. A sonogram obtained several hours after birth demonstrated large, echogenic kidneys (Fig. 3). The right kidney measured 49 mm, the left 48 mm. There was no hydronephrosis. The baby's neonatal course was complicated by hepatitis and intraventricular hemorrhage. A renal biopsy at 10 weeks of age showed congenital nephrotic syndrome of the Finnish type. During the first year of life, he developed pyloric stenosis, hepatic fibrosis associated with alpha-1-antitrypsin deficiency, gastroesophageal reflux, and failure to thrive. He sustained two cerebrovascular accidents owing to hypercoa· gulability of the nephrotic syndrome, treated with prophy· lactic aspirin. He was managed with nutritional supplemen• tation and intravenous albumen infusions. At 1 year of age, the kidneys remained enlarged and echogenic (Fig. 4), He underwent nephrectomy at age 16 months, peritoneal di alysis, and successful living related donor renal transplant at 18 months. He remains significantly developmentally delayed at 2 years of age.
© 1992 by the American Institute of Ultrasound in Medicine• I Ultrasound Med 11:113- 116, 1992 • 0278-4297/92/ $3.50
114
NEPHROTIC SYNDROME
JUltrasound Med 11:113- 116, 1992
DISCUSSION
Figure 1 Coronal scan through the fetal abdomen at 17 weeks of menstrual age. The kidneys appear slightly echo~ genie but are of nonnal size, the right kidney (RK) measuring 19 mm in length, the left kidney (LK) 17 mm.
Congenital nephrotic syndrome of the Finnish type (CNF) is a rare, autosomal recessive disorder characterized pathologically by dilated renal collecting tubules, fusion of basement membrane foot processes, and proliferation of mesangial cells.3 Along with diffuse mesangial sclerosis, it is one of the two major congenital nephroses. Renal protein loss invariably begins in utero and leads to markedly elevated maternal serum and amniotic fluid APP-levels. The fetus is typically born prematurely and is of low birth weight. The placenta is large and edematous. 3 The prognosis for neonates born with CNF is generally poor, with half of conservatively managed patients dying before the age 6 months, and nearly all by 4 years. 3 Renal transplantation has offered hope for increased survival; Holmberg and coworkers reported excellent results in eight children who underwent
A Figure 2 Transverse (A) and longitudinal (B) scans through the fetal kidneys at 25 weeks of menstrual age. The kidneys (RK, LK) are of normal echogenicity but are now enlarged, both measuring 36 mm in length.
JUltrasound Med 11:113-116, 1992
MOORE ET AL
115
Figure 3 Longitudinal scan through the right kidney several hours after birth at 33 weeks of menstrual age. The kidney is echogenic and large, measuring 49 mm in length.
B
transplantation for CNF. 4 Neonatal signs of CNF include proteinuria, hypoalbuminemia, edema, and failure to thrive. Respiratory difficulties are often present at birth. 3 Elevated maternal serum AFP may be the first sign of CNF. This abnormal laboratory value is nonspecific and may result from open neural tube defects, abdominal wall defects, multiple gestation, incorrect estimation of gestational age, or maternal hepatoma. The patient we studied had a markedly elevated amniotic fluid alpha fetoprotein (AFAFP), 43.8 MoM, the highest yet recorded at this institution. This narrows the differential diagnosis. Markedly elevated AFAFP (greater than 10 MoM) has been seen with congenital nephrotic syndrome, maternal hepatoma, and abdominal pregnancy, but only occasionally with neural tube defects, abdominal wall defects, fetal demise, and oligohydramnios. Recent data suggest that a second amniocentesis may be warranted in pregnancies when nephrosis is suspected to detect increasing amniotic fluid AFP levels. 5 The sonographic findings in CNF in neonates have
been published in several case reports. Alkrinawi and colleagues described a 10 week old infant, 6 Graif and coworkers a 3 month old infant, 7 and Perale and associates a 14 month old infant. 8 In each case, the kidneys were large and echogenic. Additionally, Alkrinawi and colleagues described both relative hypoechogenicity of the renal pyramids and a hypoechoic subcapsular layer of renal parenchyma. Perale and coworkers found similar areas of decreased echogenT icity in a follow-up study of their patient at 4 years 6 months of age. 8 The renal sonographic findings in the fetus we studied varied. At 16 weeks of gestation the kidneys were slightly echogenic and of normal size. Later they were Figure 4 Longitudinal scan through the right kidney at 1 year of age. The kidney remains enlarged (86 mm) and echogenic.
116
NEPHROTIC SYNDROME
of normal echogenicity. By 25 weeks the kidneys were increased in size. At birth they were both large and echogenic, an appearance compatible with earlier re· ports. The amniotic fluid volume was normal throughout the pregnancy. The placenta became larger than expected only late in pregnancy. In conclusion, a markedly elevated maternal serum and amniotic fluid AFP should alert the sonographer to the possible diagnosis of congenital nephrosis of the Finnish type. The sonogram of the fetal kidneys may show normal or echogenic parenchyma and normal or enlarged renal size.
REFERENCES 1. Lawson T, Foley WO, Berland L, et al: Ultrasonic evaluation of fetal kidneys. Radiology 138:153, 1981
J Ultrasound Med l 1:113- 11 6, 1992
2. Hoddick W, Mahony B, Callen P, et al: Placental thick~ ness. J Ultrasound Med 4;479, 1985 3. Norio R, Rapola J: Congenital and infantile nephrotic syndromes. Progr Clin Biol Res 305:179, 1989 4. Holmberg C, Jalanko H, Koskimies 0, et al: Renal trans• plantation in children with congenital nephrotic syn· drome of the Finnish type. Transplant Proc 22:158, 1990 5. Crandall BF, Matsumoto M: Risks associated with an elevated amniotic fluid alpha-fetoprotein level. Am J Med Genet 39:64, 1991 6. Alkrinawi S, Gradus DB, Goldstein J, et al: Ultrasono• graphic pattern of congenital nephrotic syndrome of Finnish type. J Clinical Ultrasound 17:443, 1989 7. Graif M, Lison M, Strauss S, et al: Congenital nephrosis: Ultrasonographic features. Pediatr Radio! 12:154, 1982 8. Perale R, Talenti E, Lubrano G, et al: Late ultrasono· graphic pattern in congenital nephrotic syndrome of Fin~ nish type. Pediatr Radiol 18:71, 1988
CASE REPORT The affected pregnancy was the first of a nonconsanguineous Caucasian couple of English descent. The parents were each 27 years of age, had had no prior pregnancies, were in good health, and had no significant medical illness. The early pregnancy was uncomplicated. A maternal serum alpha· fetoprotein (MSAFP) sample was obtained at 16 weeks of gestation with dating based on a 6-week sonographic examination. The MSAFP value returned at 9.4 multiples of the median (MoM). A sonogram obtained at 17.3 weeks of gestation revealed biometry consistent with dating, normal amniotic fluid volume, normal intracranial anatomy, and normal spine, ventral wall, and bladder. The kidneys appeared slightly echogenic but were normal in size using tables developed by Lawson and coworkers 1 (Fig. 1). The MSAFP evaluation repeated at 17.8 weeks, was 9.3 MoM. The family was counseled regarding the significant risks of such an elevated MSAFP level as well as the limitations of ultrasound examination. At 18.3 weeks, a repeat sonogram was obtained and showed appropriate interval growth. The kidneys on this examination were of normal size and echogenicity and no anatomic abnormalities were detected. An amniocentesis was performed, which revealed a karyotype of 46,XY. The AFP concentration in the fluid was 46.4 mg per di, or 43.8 MoM; the acetylcholinesterase was negative. The family was in· formed of the risk of congenital nephrotic syndrome and of the possibility of an undetected anatomic abnormality. Be· cause of high likelihood of congenital nephrotic syndrome, Received April 17, 1991, from the Departments of• Radiology,
t Medicine and Reproductive Medicine, and t Pediatrics, University
of California, San Diego, California. Revised manuscript accepted for publication August 21. 1991. Address correspondence and reprint requests to Dolores Pretorius: UCSD Medical Center, Division of Diagnostic Ultrasound (8759), 225 Dickinson Street, San Diego, CA 92103-8759.
prenatal con&ultation with a pediatric nephrologist was ar· ranged for the family. A follow-up sonogram at 25 weeks of gestation demonstrated normal renal echogenicity but for the first time showed bila teral renal enlargement, both kidneys measuring 36 mm (Fig. 2). The remainder of the study, including am· niotic fluid volume, continued to be nonnal. Examinations at 26 and 30 weeks showed progressive renal enlargement, with both kidneys measuring 43 mm in length on the later study. The placenta, equivocally thick on earlier studies, measured 42 mm on the 30-week examination, greater than two standard deviations above the mean established by Haddick and colleagues. 2 A 1450 gram boy was born at 33 weeks of gestation after premature labor with fetal distress. Apgar scores were 5 and 7 at 1 and 5 minutes, respectively. Meconium staining was present at delivery, and the baby required a brief period of intubation for respiratory distress. Physical examination revealed large, firm kidneys. Massive proteinuria was present from birth. A sonogram obtained several hours after birth demonstrated large, echogenic kidneys (Fig. 3). The right kidney measured 49 mm, the left 48 mm. There was no hydronephrosis. The baby's neonatal course was complicated by hepatitis and intraventricular hemorrhage. A renal biopsy at 10 weeks of age showed congenital nephrotic syndrome of the Finnish type. During the first year of life, he developed pyloric stenosis, hepatic fibrosis associated with alpha-1-antitrypsin deficiency, gastroesophageal reflux, and failure to thrive. He sustained two cerebrovascular accidents owing to hypercoa· gulability of the nephrotic syndrome, treated with prophy· lactic aspirin. He was managed with nutritional supplemen• tation and intravenous albumen infusions. At 1 year of age, the kidneys remained enlarged and echogenic (Fig. 4), He underwent nephrectomy at age 16 months, peritoneal di alysis, and successful living related donor renal transplant at 18 months. He remains significantly developmentally delayed at 2 years of age.
© 1992 by the American Institute of Ultrasound in Medicine• I Ultrasound Med 11:113- 116, 1992 • 0278-4297/92/ $3.50
114
NEPHROTIC SYNDROME
JUltrasound Med 11:113- 116, 1992
DISCUSSION
Figure 1 Coronal scan through the fetal abdomen at 17 weeks of menstrual age. The kidneys appear slightly echo~ genie but are of nonnal size, the right kidney (RK) measuring 19 mm in length, the left kidney (LK) 17 mm.
Congenital nephrotic syndrome of the Finnish type (CNF) is a rare, autosomal recessive disorder characterized pathologically by dilated renal collecting tubules, fusion of basement membrane foot processes, and proliferation of mesangial cells.3 Along with diffuse mesangial sclerosis, it is one of the two major congenital nephroses. Renal protein loss invariably begins in utero and leads to markedly elevated maternal serum and amniotic fluid APP-levels. The fetus is typically born prematurely and is of low birth weight. The placenta is large and edematous. 3 The prognosis for neonates born with CNF is generally poor, with half of conservatively managed patients dying before the age 6 months, and nearly all by 4 years. 3 Renal transplantation has offered hope for increased survival; Holmberg and coworkers reported excellent results in eight children who underwent
A Figure 2 Transverse (A) and longitudinal (B) scans through the fetal kidneys at 25 weeks of menstrual age. The kidneys (RK, LK) are of normal echogenicity but are now enlarged, both measuring 36 mm in length.
JUltrasound Med 11:113-116, 1992
MOORE ET AL
115
Figure 3 Longitudinal scan through the right kidney several hours after birth at 33 weeks of menstrual age. The kidney is echogenic and large, measuring 49 mm in length.
B
transplantation for CNF. 4 Neonatal signs of CNF include proteinuria, hypoalbuminemia, edema, and failure to thrive. Respiratory difficulties are often present at birth. 3 Elevated maternal serum AFP may be the first sign of CNF. This abnormal laboratory value is nonspecific and may result from open neural tube defects, abdominal wall defects, multiple gestation, incorrect estimation of gestational age, or maternal hepatoma. The patient we studied had a markedly elevated amniotic fluid alpha fetoprotein (AFAFP), 43.8 MoM, the highest yet recorded at this institution. This narrows the differential diagnosis. Markedly elevated AFAFP (greater than 10 MoM) has been seen with congenital nephrotic syndrome, maternal hepatoma, and abdominal pregnancy, but only occasionally with neural tube defects, abdominal wall defects, fetal demise, and oligohydramnios. Recent data suggest that a second amniocentesis may be warranted in pregnancies when nephrosis is suspected to detect increasing amniotic fluid AFP levels. 5 The sonographic findings in CNF in neonates have
been published in several case reports. Alkrinawi and colleagues described a 10 week old infant, 6 Graif and coworkers a 3 month old infant, 7 and Perale and associates a 14 month old infant. 8 In each case, the kidneys were large and echogenic. Additionally, Alkrinawi and colleagues described both relative hypoechogenicity of the renal pyramids and a hypoechoic subcapsular layer of renal parenchyma. Perale and coworkers found similar areas of decreased echogenT icity in a follow-up study of their patient at 4 years 6 months of age. 8 The renal sonographic findings in the fetus we studied varied. At 16 weeks of gestation the kidneys were slightly echogenic and of normal size. Later they were Figure 4 Longitudinal scan through the right kidney at 1 year of age. The kidney remains enlarged (86 mm) and echogenic.
116
NEPHROTIC SYNDROME
of normal echogenicity. By 25 weeks the kidneys were increased in size. At birth they were both large and echogenic, an appearance compatible with earlier re· ports. The amniotic fluid volume was normal throughout the pregnancy. The placenta became larger than expected only late in pregnancy. In conclusion, a markedly elevated maternal serum and amniotic fluid AFP should alert the sonographer to the possible diagnosis of congenital nephrosis of the Finnish type. The sonogram of the fetal kidneys may show normal or echogenic parenchyma and normal or enlarged renal size.
REFERENCES 1. Lawson T, Foley WO, Berland L, et al: Ultrasonic evaluation of fetal kidneys. Radiology 138:153, 1981
J Ultrasound Med l 1:113- 11 6, 1992
2. Hoddick W, Mahony B, Callen P, et al: Placental thick~ ness. J Ultrasound Med 4;479, 1985 3. Norio R, Rapola J: Congenital and infantile nephrotic syndromes. Progr Clin Biol Res 305:179, 1989 4. Holmberg C, Jalanko H, Koskimies 0, et al: Renal trans• plantation in children with congenital nephrotic syn· drome of the Finnish type. Transplant Proc 22:158, 1990 5. Crandall BF, Matsumoto M: Risks associated with an elevated amniotic fluid alpha-fetoprotein level. Am J Med Genet 39:64, 1991 6. Alkrinawi S, Gradus DB, Goldstein J, et al: Ultrasono• graphic pattern of congenital nephrotic syndrome of Finnish type. J Clinical Ultrasound 17:443, 1989 7. Graif M, Lison M, Strauss S, et al: Congenital nephrosis: Ultrasonographic features. Pediatr Radio! 12:154, 1982 8. Perale R, Talenti E, Lubrano G, et al: Late ultrasono· graphic pattern in congenital nephrotic syndrome of Fin~ nish type. Pediatr Radiol 18:71, 1988
