American Journal of Medical Genetics 1657-60 (1983)

Possible New Autosomal Recessive Syndrome With Unusual Renal Histopathological Changes

Judith E. Allanson, J.T. Pantzar, and P.M. MacLeod

Clinical Genetics Unit, University of British Columbia, Grace Hospital (J. €.A); Department of Pathology, Children’s Hospital (J. T P.), Vancouver, British Columbia; and Division of Medical Genetics, Department of Pediatrics (P. M. M.) Queens University, Kingston, Ontario, Canada

We report a couple with repeated pregnancy loss-two spontaneous first trimester abortions and two stillbirths with diffuse hypoplasia of the renal tubules. Both parents have been investigated to exclude occult unilateral renal agenesis. We raise the possibility that this is a new autosomal recessive condition.

Key words: repeated pregnancy loss, bilateral renal abnormality, minimal-change glomerulone- phritis, autosomal recessive inheritance

CLINICAL REPORT

We report on a nonconsanguineous Chinese couple from Borneo who had two early pregnancy losses followed by two stillborn females each with bilateral renal histological abnormalities. No examination of the first abortus is available. The second was found to have trisomy 16.

Two months after the second abortion and prior to the stillbirth the 32-year-old father developed pleural effusions, ascites, proteinuria (14-16 gm protein daily), hypoproteinaemia, hypercholesterolaemia, and hypertriglyceridaemia. On renal bi- opsy he had “minimal change” glomerulonephritis with no abnormality of the proxi- mal convoluted tubules. He was treated with furosemide and prednisolone, which produced remission after 1 mo. Six months later he relapsed and he was treated with

Received for publication October 23, 1982; revision received March 30, 1983

Address reprint requests to Dr. Judith E. Allanson, Clinical Genetics Unit, University of British Columbia, Grace Hospital, 4490 Oak Street, Vancouver, BC, Canada V6H 3V5.

0 1983 Alan R. Liss, Inc.

58 Allanson, Pantzar, and MacLeod

three further courses of steroids. After a second relapse chlorambucil was added and produced a further remission after 2 mo treatment. Two relapses over the next 2 yr necessitated treatment with cyclophosphamide for 1 mo. He remains in remission.

Fourteen weeks after the last dose of cyclophosphamide the couple conceived. Oligohydramnios ensued and at 34 wk a female infant was stillborn with pulmonary hypoplasia, hypertelorism, and hypermobile wrist and ankle joints. There was amnion nodosum but no cardiac malformation. Chromosomes were normal.

Fourteen months later, at 36 wk gestation, a second stillborn female was delivered with similar facial appearance, pulmonary hypoplasia, microcephaly, sub- ependymal plate cyst, tetralogy of Fallot with patent ductus arteriosus, hyperextension at wrists and ankles, flexion contractures of thighs and legs, rocker-bottom feet, left simian crease, and abnormal body proportion. Chromosomes again were normal.

At autopsy, the kidneys from both infants were of normal size, shape, and weight. The cut surface had an evenly granular cortex with effacement of normal markings and loss of corticomedullary demarcation. The pelvicalyceal systems and ureters were slightly hypoplastic. Distal urinary tract was normal. Histological char- acteristics were similar in both cases: glomerulogenesis just completed (consistent with 34-36 wk gestation), glomeruli normal; several intraluminal tubular calcifica- tions were present; and normal proximal convoluted tubules were absent and all tubules appeared abnormally developed, primitive, and reminiscent of collecting tubules (Figs. 1 and 2). The interstitium showed increased fibrous connective tissues. The mesenchymal component was normal. No cartilage was present. Inflammation, viral inclusions. and infarctions were absent. Vessels were normal.

DISCUSSION

We have not found any reports of renal abnormality with the same microscopic characteristics as those outlined above. Although the kidneys were abnormal they were not dysplastic in the strict developmental sense. Some of the histological changes are similar to those described by Zuelzer et a1 [1951] but the major changes in his cases (hypoplasia and infarction) are not found in the present cases. Impaired perfu- sion for several reasons could be associated with the uniformly underdeveloped tubules seen in our cases. We suspect we are dealing with a newly recognized entity and, because of its occurrence in two sisters, think it is an autosomal recessive trait. However, there is no evidence of consanguinity.

Bilateral renal abnormality may be accompanied by anomalies that occur sec- ondary to the lack of renal function and resultant oligohydramnios, such as Potter’s facies, congenital contractures, club foot, congenital dislocation of the hip, spade-like hands, and pulmonary hypoplasia.

The presence of minimal change glomerulonephritis in the father raises the possibility that carriers of this autosomal recessive gene are predisposed to renal disease. It is important to note that the major histological abnormality found in the autopsy specimens was absence of normal proximal convoluted tubules. Abnormality of the tubules is not a characteristic of minimal change glomerulonephritis.

New Syndrome 59

Fig. 1 . Kidney of case I . Note lack of normal cortical landmarks such as medullary rays. X25: haematoxylin and eosin.

Fig. 2. Same case showing abnormally developed tubules. ~400: haematoxylin and eosin.

60 Allanson, Pantzar, and MacLeod

ACKNOWLEDGMENTS

We thank Dr. J. Bernstein for reviewing the microscopic slides of the kidneys. We also extend our thanks to Dr. Margaret Norman for her help with the manuscript.

REFERENCES

Zuelzer WW, Charles S , Kurnetz R, Newton WA, Fallon R (1951): Circulatory diseases of the kidneys in infancy and childhood. Am J Dis Child 81:l-46.