Postaxial Polydactyly, Ulnar Ray Dysgenesis, andRenal Cystic Dysplasia in Sibs

Bernard S. Kaplan* and Richard D. BellahDivision of Nephrology Department of Pediatrics, and Department of Radiology, The Children’s Hospital ofPhiladelphia, University of Pennsylvania, Philadelphia, Pennsylvania

We describe two brothers with variable ex-pression of a unique syndrome. One sib haspostaxial polydactyly of the right hand andfeet, two digits on the left hand (a thumband first digit), bilateral ulnar ray dysgen-esis, ectrodactyly of one hand, and ultra-sonic evidence of cystic kidneys. Hisbrother has postaxial polydactyly and smallkidneys. The parents and a third sib are nor-mal. They do not have the Pallister ulnar-mammary syndrome but may have an un-usual form of the Weyers oligodactyly syn-drome. This appears to be the first report ofan acro-renal syndrome with ulnar dysgen-esis, oligodactyly, polydactyly, and dysplas-tic kidneys. Am. J. Med. Genet. 87:426–429,1999. © 1999 Wiley-Liss, Inc.

KEY WORDS: postaxial polydactyly; ulnarray dysgenesis; split handanomaly; dysplastic kidneys

INTRODUCTION

Although there are many syndromes of renal and/orgenitorenal anomalies with radial ray dysostoses[Evans et al., 1992; Van Allen, 1993], we are aware ofonly two syndromes in which renal anomalies concurwith ulnar ray dysgenesis [Weyers, 1957; Elejalde etal., 1985; Schinzel, 1987; Gonzales et al., 1976]. Wereport on two brothers with postaxial polydactyly anddysplastic kidneys. The older brother also has ectrodac-tyly of his right hand and an abnormal right ulna. Theydo not have the Pallister ulnar-mammary syndromebut may have an unusual form of the Weyers oligodac-tyly syndrome. Inheritance seems to be autosomal re-cessive, although X-linked transmission is not ruledout.

CLINICAL REPORTSPatient 1

This patient was born at 37 weeks after a normalgestation. The primigravid mother, was a 26-year-oldwoman. The baby was delivered by emergency cesar-ean section because of persistent decelerations andbreech presentation. Apgar scores were 9 and 9 at 1and 5 min, respectively. Prenatal ultrasound findingswere interpreted as showing bilateral cystic kidneysand possible coarctation of the aorta. Chromosomes onamniotic cells were apparently normal (46,XY). Birthweight was 2,634 g (10th centile) and length 43 cm (<10th centile). Examination at birth showed postaxialdigits on the right hand and both feet. There were twodigits on the left hand; one seemed to be a thumb, andthe other a first digit (Fig. 1). There was a contracture

*Correspondence to: Bernard S. Kaplan, M.B., B.Ch., Divisionof Nephrology, The Children’s Hospital of Philadelphia, Univer-sity of Pennsylvania, 34th Street and Civic Center Boulevard,Philadelphia, PA 19104. E-mail: kaplanb@email.chop.edu

Received 23 March 1999; Accepted 30 August 1999

Fig. 1. Case 1. Frontal view of the right hand shows post-axial poly-dactyly. The proximal and distal phalanges of the extra digit are fairly wellformed. A rudimentary duplicated metacarpal arises from the base of thefifth metacarpal.

American Journal of Medical Genetics 87:426–429 (1999)

© 1999 Wiley-Liss, Inc.

at the left elbow with 30° mobility (Fig. 2) and meta-tarsus adductus of the right foot (Fig. 3). There was alarge metopic suture, and the mandible was small. Hehad hypertelorism with an outer canthal distance of 6.5

Fig. 2. Case 1, left upper limb. Absence of complete elbow crease, cen-tral ray deficiency, and absence of ulna. The radius is short.

Fig. 3. Case 1. Feet demonstrate post-axial polydactyly with well-formed toes (including metatarsals and phalanges) adjacent to normal fifth digits.

Fig. 4. Case 1, axial skeleton. There is rightward deviation of the sa-crum (arrow). The pelvis, vertebral bodies, and ribs are normal.

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Fig. 5. Case 1, left kidney sonogram. The longitudinal view shows a “featureless kidney” markedly increased in echogenicity but normal in length (A).High resolution scans show small cysts (arrows) at the periphery (B). The right kidney (not shown) was similarly affected.

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cm and inner canthal distance of 3.0 cm. The cord con-tained three vessels. There were no cardiac murmurs.The chest, abdomen, and penis were normal, and thetestes were descended. At birth the serum creatinineconcentration was 1.3 mg/dl. This increased to 1.8 mg/dl by day 3 and gradually decreased to 0.6 mg/dl overthe next 2 months. At 2.5 years he had severe consti-pation. A plain film of the abdomen showed a largeamount of feces and a malformed sacrum (Fig. 4). Amagnetic resonance imaging showed no evidence of atethered cord, but there was a small sinus tract in themidline at the level of the coccyx. A barium enema wasnormal. Renal ultrasonography (Fig. 5A) showed fea-tureless kidneys of normal size with markedly in-creased echogenicity and small peripheral cysts (Fig.5B). At age 5 years he had polydipsia and polyuria.Weight was 19.9 kg (95th centile) and height 94.1 cm (<5th centile). Blood pressure was 91/71 mm Hg.

Patient 2

This patient was examined at age 11 months (age 10months). Weight was 8.14 kg (5th centile) and lengthwas 46 cm (25th centile). His OFC was 46 cm (25thcentile), and he had hypertelorism. There was bilateralpost-axial polydactyly of the feet and right postaxialpolydactyly of the hand. There were no other anoma-lies. Specifically, he did not have absent ulnae or ab-normal legs. The sacrum was not studied. The bloodurea nitrogen (BUN) was 13 mg/dl, and the serum cre-atinine concentration was 0.5 mg/dl. Renal ultrasonog-raphy showed enlarged kidneys with loss of the cortico-medullary junction and no cysts. A 2-year-old sisterand the parents were normal.

DISCUSSION

With the exception of the Weyers oligodactyly syn-drome [Weyers, 1957] and the Pallister ulnar-mammary syndrome [Schinzel, 1987; Gonzales et al.,1976], all of the reported acro-renal syndromes haveinvolved the radius [Van Allen, 1993]. Weyers [1957]described two unrelated patients with a deficiency ofulnar and fibular rays, antecubital pterygia, reducedsternal segments, and malformations of kidney andspleen. One patient had two fingers on each hand, andthe other patient had two fingers on the right and onemalformed finger on the other hand. Elejalde et al.[1985] reported on two sibs with similar anomalies.The male had oligodactyly, and the female had severebilateral hydronephrosis. Both had very short fibulaeand ulnae. Our patients have similar anomalies tothose described by Weyers [1957] and Elejalde et al.[1985] and may have an unusual form of the Weyersoligodactyly syndrome. The polydactyly may also rep-resent an unusual manifestation of the Weyers syn-drome. If this is correct, we suggest that the term, Wey-ers oligodactyly syndrome, be changed to Weyers oligo-dactyly/polydactyly renal syndrome.

The autosomal dominant Pallister ulnar-mammary

syndrome comprises ulnar ray defects, oligodactyly,aplasia or hypoplasia of the mammary glands andnipples, hypoplasia of the apocrine glands, genitalanomalies, and unilateral renal agenesis [Schinzel,1987; Gonzales et al., 1976; Van Allen, 1993]. Muta-tions in the T-box gene, TBX3 have been found in pa-tients with Pallister ulnar mammary syndrome [Bam-shad et al., 1997]. There were no obvious phenotypicdifferences between individuals who had missense mu-tations, deletions, or frameshifts [Bamshad et al.,1999]. Our patients do not have the Pallister ulnar-mammary syndrome, and their parents are normal.

The nature of the renal histological abnormality inour patients is not known. We considered doing a kid-ney biopsy on case 1 neonatally when the serum creat-inine concentration was elevated but decided not to doso because there would be no advantage to be gainedfrom this procedure for the patient. Therefore, we haveno histopathological evidence that the kidneys are dys-plastic. However, small, echodense kidneys with nu-merous small cysts invariably are dysplastic when ex-amined microscopically.

Structural abnormalities of chromosome have beenreported in an infant with ulnar ray aplasia, postaxialoligodactyly, and apparently normal kidneys [Gurrieriet al., 1995]. The syndrome in our patients may be dueto an X-linked or autosomal recessive mutation.

ACKNOWLEDGMENTS

We thank the parents for permission to publish thispaper.

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