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A further case of vertical transmission of proximal femoral focal deficiency

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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 [1986], 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
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,
*Correspondence to: Dipl.-Med. Axel Bohring, Department of
Pediatrics, Ostholstein Kliniken, Janusstraße 22, D-23701 Eutin,
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.
Fig. 2.
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
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-
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.
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 [1986] and
Sorge et al.[1995]. Also typical was the mild ectrodactyly, which either can be a specific entity as described
in a family by Deragna et al. [1966], 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.
[1995], 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]. On
the other hand, a slight affection of the proximal femoral epiphysis and the acetabulum is reported in FAH
[Coventry and Johnson, 1952]. Whether PFFD or FAH
in our family (and that of Sorge et al. [1995]) is the
correct entity will remain unsolved until the underlying pathogenetic mechanism is clear.
The pattern of inheritance in this family is most likely
autosomal-dominant with variable expressivity and penetrance. However, an X-linked form cannot be excluded.
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femoral, transmission, focal, deficiency, case, vertical, proximal
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