American Journal of Medical Genetics 71:194–196 (1997) Brief Clinical Report A Further Case of Vertical Transmission of Proximal Femoral Focal Deficiency? Axel Bohring* and Hans-Conrad Oppermann Department of Pediatrics, University of Kiel, Kiel, Germany We report on a newborn boy with congenital asymmetrically hypoplastic fibulae, lateral oligodactyly, and mild left ectrodactyly. The patient’s grandfather had a short femoral shaft with a slightly smaller collodiaphyseal angle on the left as compared to the right side, probably a proximal focal femoral deficiency (PFFD). The upper limbs were not affected in either patient. PFFD in the grandfather and hypoplastic fibulae with lateral ray defects in the grandson raise the possibility of genetic transmission, specifically autosomal-dominant inheritance with variable penetrance and expressivity. This case gives further support to the fibular developmental field concept postulated by Lewin und Opitz [1986: Am J Med Genet (Suppl) 2:215–238]. Am. J. Med. Genet. 71: 194–196, 1997. © 1997 Wiley-Liss, Inc. Based on the overlapping phenotypes, PFFD, FAH, and femur-fibula-ulna dysostosis (FFU) are by some investigators considered a single entity [Lenz and Feldmann, 1977; Lenz et al., 1993; McKusick, 1994]. According to Lewin and Opitz , these malformation complexes do overlap, but they are not identical entities within the fibular developmental field. This developmental field covers defects from the pubic portion of the pelvis, the proximal femur, the patella, the anterior cruciate ligament, the femoral condyles, the fibula, a variable number of lateral and/or axial toes, and the talus and cuboid bones, and secondarily all the nerves, muscles, arteries, and veins associated with fibular development [Haudek, 1896; O’Rahilly, 1951; Lewin and Opitz, 1986]. KEY WORDS: fibular hypoplasia; proximal femoral focal deficiency; ectrodactyly; fibular developmental field INTRODUCTION Proximal femoral focal deficiency (PFFD; McKusick 228200) is a rare anomaly, occurring with a frequency of approximately 0.2/10,000 live births [Hamanishi, 1980]. PFFD occurs as an isolated anomaly or in combination with other defects of the lower limbs (absence or hypoplasia of the patella, fibular a/hypoplasia (FAH), and absence of lateral foot rays). In most cases PFFD is sporadic and the cause is unknown. However, familial cases are described [Kelly, 1974; Keret and Timor, 1989; Sorge et al., 1995; see Lewin and Opitz, 1986]. *Correspondence to: Dipl.-Med. Axel Bohring, Department of Pediatrics, Ostholstein Kliniken, Janusstraße 22, D-23701 Eutin, Germany. Received 9 August 1996; Accepted 25 December 1996 © 1997 Wiley-Liss, Inc. Fig. 1. Leg length discrepancy due to shortness of the left lower limb. PFFD Fig. 2. CLINICAL REPORT The boy is the first child of a 29-year-old mother and a 28-year-old father. The couple is healthy and no consanguinity is known. No spontaneous abortions were reported. The pregnancy was unremarkable. There were no infections or medications, and no (pre)diabetes. The boy was delivered spontaneously at term. Birth weight was 3,030 g (10th centile), length 47 cm (<3rd centile), and occipitofrontal head circumference (OFC) 35 cm (25–50th centile). He lacked lateral toes on both feet, and only toes I–III on the left and toes I–IV (or I–III and V) on the right were present (Figs. 1 and 2). On the right side there also was partial cutaneous II–III syndactyly. The outer malleoli appeared hypoplastic. The left lower limb was shorter than the right. The left tibia was incurved, with a dimple over the convexity. Apart from this there were no further external anomalies; the upper limbs were normal, and there was no craniosynostosis. According to roentgenograms of the pelvis and lower limbs (Figs. 3 and 4), pelvis, symphysis, and ossa ischiadica were normal. Both femora were normal in shape 195 Left (a) and right (b, c) feet. and 7.0 cm long. The distal femoral epiphyses were ossified according to the gestational age on both sides, but smaller on the left than on the right side. The right tibia was 5.6 cm long and normal in shape, and the right fibula was 5.3 cm long. The left tibia was curved and shorter (5.1 cm), and the left fibula was 4.2 cm and clearly shorter than on the right side. The right foot had 4 normal toes, the left foot had only 3 toes, and the second metatarsal bone was hypoplastic, as was the first phalanx. Both calcanei were present, but the left was smaller than the right. The talus, which should have been visible according to gestational age, was not visible on either side. The upper limbs were radiologically normal, except for their advanced bone age (capitatum and hamatum were present at birth). Kidneys were normal and there were no genitourinary tract anomalies, as shown by ultrasound. Ultrasonography of the hips was normal. Chromosomes on G-banding from peripheral lymphocytes showed a normal male karyotype (46, XY). The parents had normal limbs. However, the mater- 196 Bohring and Oppermann Fig. 3. Anteroposterior radiograph of the legs. nal grandfather had a leg length discrepancy of 1.6 cm, because of a shorter left femoral shaft with a slightly smaller collodiaphyseal angle on the left side, as seen on radiographs. The femur was normal in shape. In the grandfather’s history and in the films there were no signs of trauma, infection, degenerative disorder, or hip dislocation. The family history was otherwise unremarkable. DISCUSSION The patient had typical findings of FAH with fibular hypoplasia, lateral oligodactyly, mild ectrodactyly, ossification anomalies of the talus, and calcaneus and femoral condyles with asymmetry on both sides. The affected structures are part of the fibular developmental field, as postulated by Lewin and Opitz  and Sorge et al.. Also typical was the mild ectrodactyly, which either can be a specific entity as described in a family by Deragna et al. , or (as suggested in our case presented here) can be part of the complex field defect [Bidder, 1888; Hootnick et al., 1980]. The curving of the left tibia in our case is probably a secondary defect. Whether the advanced bone age in the hands is a normal variant, or has a causal relation- Fig. 4. Anteroposterior radiograph of both feet. Note the hypoplastic metatarsal bone and first phalanx of left toe II (mild ectrodactyly). ship with the other defects, cannot be decided with certainty. FAH is mostly a sporadic, nonsyndromal, and in most cases a nongenetic event. In the family described here the maternal grandfather had isolated shortness of the femoral shaft and a slightly smaller collodiaphyseal angle, which is most probably congenital, as there were no signs of infection, fracture, or degeneration. This finding could be a normal variant, which might not be related to the anomalies seen in the boy. However, we would rather suggest that the findings in the grandfather and grandson are different expressions of a familial form of PFFD. The anomalies described are similar (but inversely placed in the pedigree) to patients 2 and 3 (son and father) reported by Sorge et al. , where an isolated PFFD was present in the son and bilateral foot malformations plus tibial and fibular hypoplasia in the father. PFFD is frequently correlated with a fibular defect and absence of lateral foot rays [Hamanishi, 1980]. 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