Femur, Unilateral Bifid, With Monodactylous Ectrodactyly

Clinical Features

Gollop et al. (1980) described 2 brothers, each with 1 normal upper limb; 1 had tridactylous ectrodactyly of 1 hand with normal radius and ulna, and the other had monodactyly of 1 hand with absent ulna. Both had monodactyly of the feet, absence of the tibias, and unilateral bifurcation of the femur. A sister of the paternal grandfather was purportedly similarly affected. The mode of inheritance was considered unclear.

Wolfgang (1984) reported an Amish newborn with a rare combination of congenital anomalies, including bifurcation of the right femur with ipsilateral complete tibial hemimelia, congenital diastasis of the left ankle, and bilateral central defects of the hand.

Kohn et al. (1989) reported 2 unrelated families, each with 2 affected offspring with bifid femur, absent tibia, and ectrodactyly. In each family, the healthy parents were consanguineous. The authors suggested that these observations established this combination of malformations as a causally heterogeneous disorder with both autosomal dominant (119100) and autosomal recessive forms and, therefore, as a developmental field defect.

Lurie and Ilyina (1986) proposed the eponym Gollop-Wolfgang complex (GWC) for the combination of femoral bifurcation with hand ectrodactyly. Endo et al. (1998) found a total of 12 reported cases and added the case of a Japanese girl with a unique form of this malformation complex. Both hands and feet were involved and the involvement was bilateral.

Autosomal recessive inheritance seemed to obtain in the case of a child described by Raas-Rothschild et al. (1999). Features were bifid femur, absent tibiae, hypoplastic hallux, bilateral clubfeet, congenital heart defects, and segmentation anomalies of the spine and ribs. The parents were an Arab Muslim couple related as first cousins once removed who came from a region where other consanguineous families with similarly affected individuals had been reported (Kohn et al., 1989). Raas-Rothschild et al. (1999) suggested that identification of the responsible gene(s) will shed light on whether both a dominant and a recessive form of tibial aplasia with ectrodactyly/Gollop-Wolfgang complex exist.

Erickson (2005) reported 2 unrelated infants with absent tibiae and bifid femur showing phenotypic overlap with the Gollop-Wolfgang complex. Both also had clubfeet and congenital heart defects, similar to the patient reported by Raas-Rothschild et al. (1999). Additional features included cleft lip and palate, increased spinal fluid, and lissencephaly in 1 patient and tracheoesophageal fistula in the other patient. Both patients died in infancy.

Fiogbe et al. (2010) described 3 unrelated infants from Benin, West Africa, 2 boys and a girl, with femoral bifurcation and tibial aplasia. One boy had right-sided femoral bifurcation with agenesis of the patella, tibia, talus, and 1 metatarsal, and varus equinus of the right foot; he also had an absent third ray of the left foot and partial syndactyly of the first and second toes. The second boy had bilateral tibial aplasia and varus equinus, with right-sided femoral bifurcation. The girl had right-sided femoral bifurcation, tibial agenesis, pseudarthrosis of the fibula and varus equinus; her left lower extremity was normal.

Cytogenetics

Asamoah et al. (2004) described a patient with a deletion in the proximal part of chromosome 8q: 46,XY,del(8)(q11.23q13.3). The patient was severely affected with a variety of congenital malformations, including femoral bifurcation and bilateral absence of the fibula. Asamoah et al. (2004), like others before them, suggested that there may be genes important in bone/limb formation in the proximal region of 8q. Okumus and Uner (2007) suggested that the patient described by Asamoah et al. (2004) did not have bilateral absence of the fibula but rather bilateral absence of the tibia, consistent with the diagnosis of Gollop-Wolfgang complex. Asamoah (2007) argued that this patient did not have Gollop-Wolfgang complex but a multiple congenital anomaly syndrome secondary to the 8q chromosomal deletion (8q11-q13).