Keywords
bifid femur - ectrodactyly - Gollop-Wolfgang complex - hemimelia
Introduction
Gollop-Wolfgang complex is defined as the presence of a distal bifid femur and tibial
hemimelia with or without hand ectrodactyly.[1]
[2]
[3]
[4]
[5]
[6] Most cases of Gollop-Wolfgang complex are accompanied by other congenital defects,
such as the VACTERL (vertebral anomalies, anal atresia, cardiovascular anomalies—most
commonly ventricular septal defect [VSD], tracheoesophageal fistula, esophageal atresia,
renal anomalies, and limb defects—most commonly radial ray defects) sequence.[4]
[5]
[6]
[7]
[8]
According to the U.S. Office of Rare Diseases of the National Institute of Health,
there have been only 200 cases reported until now.[1] Gollop-Wolfgang complex is documented to have an incidence of ∼1:1,000,000 live
births.[5]
[7]
[9] The etiology of Gollop-Wolfgang complex is postulated to be an error in the complex
genetic control of limb development, but the exact cause remains unclear.[1]
[2]
[3] The mode of inheritance is autosomal dominant with reduced penetrance and variable
expressivity; however, neomutations cannot be excluded.[7]
[9]
Case Presentation Report
A 6-month-old African American girl born at 38 weeks by cesarean section to a 22-year-old
African American mother presented at birth, with multiple congenital anomalies including
a single umbilical artery, polyhydramnios, hemivertebrae, several appendicular, and
skeletal deformities (absence of both radii and tibias). Atrial septal defect (ASD),
VSD, and patent ductus arteriosus (PDA) had also been identified on antenatal ultrasound.
The mother followed routine prenatal care, including counseling for pregnancy termination
in another institution, and also consumed prenatal vitamins. She denied any symptoms
or complications during the pregnancy other than the aforementioned congenital abnormalities
found on the 20-week anatomy ultrasound. She also denied a family history of congenital
abnormalities, limb deficiencies, or teratogenic substance use.
At delivery, the newborn's physical examination was remarkable for cyanosis, a heart
murmur, several limb deformities including bilateral talipes equinovarus, ectrodactyly,
and protrusion of the distal femur anteromedially on the left knee joint.
The radiographs obtained at birth confirmed findings consistent with Gollop-Wolfgang
complex and a class 3 tracheoesophageal fistula. Initial chest X-ray ([Fig. 1]) showed an orogastric tube with its tip projecting at the level of the clavicles,
with gaseous distention of the stomach and proximal small bowel, all suspicious for
esophageal atresia with tracheoesophageal fistula. Prominent cardiothymic silhouette,
diffuse mild bilateral granular opacities, fusion of the first and second right ribs,
13 pairs of ribs, and a vertebral anomaly involving the left aspect of the T-10 vertebrae
were also noted. X-rays of both upper extremities ([Figs. 2] and [3]) demonstrated the absence of the radii and thumbs, significant angulation at the
wrists with respect to the normal ulna, deformed hands that were deviated proximally,
medially, and anteriorly. X-ray of the right lower extremity ([Fig. 4]) revealed a grossly normal femur, absence of one of the leg bones (difficult to
determine the specific bone due to the projection and abnormal appearance of the remaining
bone), abnormal alignment of the knees, four metatarsals and four digits, abnormal
relationship of the leg with respect to the ankle and foot, and soft tissue deformity.
X-rays of the left lower extremity ([Fig. 5]) revealed a normal proximal femur but a bifid distal femur, absence of one leg bone
as seen on the opposite leg, three metatarsal bones, and abnormal relationship at
the ankle with respect to the leg. The patient underwent several laboratory and genetic
testings. Karyotyping showed 46 XX. A complete blood count with differential was performed,
which was reported to have a normal range values, thus making Fanconi anemia or thrombocytopenia
with absent radius syndrome unlikely. The patient also underwent successful tracheoesophageal
fistula surgery confirmed by follow-up barium swallow studies.
Fig. 1 Initial anteroposterior view of the chest. Orogastric tube is visualized at the level
of the clavicles, there is gaseous distention of the stomach consistent with esophageal
atresia plus distal tracheoesophageal fistula. A widened cardiothymic silhouette is
also seen suggesting a congenital cardiac defect.
Fig. 2 Anteroposterior view of the right upper extremity. The absence of radius and thumb
leads to initially possible differentials diagnoses of thrombocytopenia-absent radius
syndrome or Fanconi anemia which were dismissed secondary to normal complete blood
count. Angulation of the wrist joint and abnormalities of the metacarpal and digital
bones are also evident.
Fig. 3 Anteroposterior view of the left upper extremity demonstrates the absence of radius
and thumb, significant angulation at the wrists with respect to the normal ulna, and
deformed hand that was deviated proximally, medially, and anteriorly.
Fig. 4 Anteroposterior (AP) view of the right lower extremity. Normal development of the
femur is evident; however, there is only one bone present in the leg. Viewing both
AP and frog-leg lateral (not shown) views, it was difficult to determine if this leg
bone was the tibia or fibula. Talipes equinovarus and bony foot abnormalities are
also present.
Fig. 5 Frog-leg lateral view of the left lower extremity reveals distal bifid femur, presence
of only one leg bone, three metatarsal bones, and abnormal relationship at the ankle
with respect to the leg.
Discussion
Gollop-Wolfgang complex belongs to the skeletal dysplastic classification of dysostoses,
which refers to malformations or absence of individual bones singly or in combination.
According to the theory of Lewin and Opitz, the growth of the lower limb is under
the control of two developmental fields, the tibia and fibula. The tibial developmental
field controls the development of the distal femur, tibia, and hallux. Thus, a defect
in this field results in distal femur duplication, tibia agenesis, and preaxial polydactyly
or ectrodactyly. The fibula developmental field controls the development of the fibula,
lateral rays of the foot, lateral knee ligaments, proximal femur, acetabulum, and
pubic bones. A defect in this field results in fibular hypoplasia, ectrodactyly, proximal
focal femoral deficiency, and deficiency of lateral knee ligament. There is a strong
association between the development of the fibula and tibial fields.[1]
[7]
[10]
Findings of Gollop-Wolfgang complex in antenatal ultrasound include increased nuchal
translucency between 11 and 14 weeks of gestation and tibial agenesis with femoral
bifurcation, clubfoot, contracture of the knees, and agenesis of the metacarpal bones
at 20 weeks. Amniocentesis can be performed for chromosomopathies, detection of chromosomal
abnormalities, and genetic counseling.[4]
[11]
[12] Prenatal exposure to valproic acid is associated with an increased risk of congenital
malformations, especially limb defects such as radial ray defects.[7]
Regarding the differential diagnosis for this disease, Forzano et al stated that the
tibial agenesis–ectrodactyly syndrome is the only condition that presents a significant
overlap with Gollop-Wolfgang complex.[12] Additional anomalies that should be excluded for the diagnosis of Gollop-Wolfgang
complex are cleft palate, cleft lip, and ocular abnormalities. In our case, the presence
of a distal bifid femur, absent radii, ectrodactyly, ASD, VSD, PDA, and tracheoesophageal
fistula leads the pediatric radiology team to a clinical and radiologic diagnosis
of Gollop-Wolfgang complex. Information regarding the mother's decision to terminate
or not to terminate the pregnancy was not available because mother's routine prenatal
care and counseling had been performed in another institution.
There are three classification systems of tibial deficiency: Kalamchi and Dawe, Jones,
and the newer Weber classification. Jones classification which is the most commonly
utilized has divided it into four types. Type 1: The tibia cannot be seen on radiographs at birth. In subtype 1a, the tibia is completely
absent and the ossific nucleus of the distal femoral epiphysis is hypoplastic. In
subtype 1b, the proximal part of tibia is present, but unossified at birth, hence
appears absent on plain radiograph. In this type, there is normal ossification of
the distal femoral epiphysis. Type 2: The proximal part of the tibia is ossified and visible on radiographs at birth,
but the distal tibia is absent. Type 3: The distal part of the tibia is ossified and visible, but the proximal portion of
the tibia is absent. This is the least common type of tibia hemimelia. Type 4: The tibia is short, and there is distal tibiofibular diastasis.[1]
[6]
[7]
In terms of treatment, prosthetic reconstruction of tibia versus knee disarticulation
depends only on the quantum of quadriceps function.[13]
[14] According to the Jones classification, our patient would classify as type 1a on
the left lower extremity and type 1b on the right lower extremity qualifying for a
knee disarticulation and realignment of the left lower extremity and tibiofibular
synostosis of the right lower extremity.
Conclusion
There are several findings in both clinical and radiographic presentations between
our case and prior documented cases of Gollop-Wolfgang complex. Regarding the etiology
of this disease, we support the theory proposed by Lewin and Opitz of lack of tibial
developmental fields causing defects in distal femur development.[15] Although our patient's condition was most likely spontaneous due to the absence
of risk factors, we also support the theories of possible associations between genetic
and environmental factors. Imaging studies such as antenatal ultrasound and postnatal
radiographs contribute to the early diagnosis of this condition. Radiographs also
assist in the classification of tibial deficiency, providing beneficial information
for the treatment.
