Case Report: Gollop-Wolfgang Complex in a 5 month old baby [version 1; peer review: 1 approved with reservations]

Skeletal dysplasias are disorders associated with a generalized abnormality in the skeleton. The Gollop-Wolfgang complex (GWC) is a limb deficiency disorder and an unusual limb malformation with highly variable manifestations. Here we report the interesting case of a 5-month old male baby from India with Gollop-Wolfgang Complex showing bifurcation of the right femur, ectrodactyly of both feet, ectrodactyly of left hand, syndactyly of right hand and unusual presentation of bilateral fibular agenesis and caudal (Sacrococcygeal) agenesis. The etiology of GWC in this 5 month old male baby could possibly be attributed to spontaneous gene mutation due to consanguineous marriage of his parents. The clinical, radiographic findings and the unusual presentation are presented in detail. This report describes a child with a typical presentation of Wolfgang-Gollop complex. The eitiology of this condition is still in doubt although some familial recurrences suggest a genetic cause. The statement in the abstract that a spontaneous mutation is possible owing to parental consanguinity does not make sense and should be deleted. In this discussion there is also a suggestion that consanguineous unions should somehow be discouraged. This is inappropriate and a breach of reproductive autonomy. Such a statement should be removed. Consanguinity is not the strong risk factor for congenital anomalies as the authors imply, conferring approximately a 2 fold enhanced risk of such problems. This assertion needs to be rebalanced. Competing believe I an appropriate of to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

This article is included in the Rare diseases collection.

Introduction
Generalized disorders of cartilage and bone have been referred to as skeletal dysplasias and are associated with a generalized abnormality in the skeleton 1 . Gollop-Wolfgang Complex (GWC) is a rare congenital limb anomaly characterized by tibial aplasia, ipsilateral bifurcation of the thighbone and ectrodactyly 2 . Ectrodactyly involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM) 3 . Very often, the anomalies of limbs, heart, digestive and urinary tracts and the lumbosacral vertebrae are also affected 4 .
In 1980, Gollop et al. described the case two brothers with ectrodactyly and unilateral bifurcation of the femur, absence of both tibiae and monodactyly of the feet 5 . In 1984, Wolfgang reported a case of right femoral bifurcation and absence of tibia and bilateral central defects of the hand 5 . Lurie and Ilyina (1986) proposed the eponym GWC for the combination of femoral bifurcation with hand ectrodactyly 6 . Endo et al. 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 2 . The etiology of GWC is most likely an error in the complex genetic control of limb development but the exact cause is still unclear 7 . GWC is listed as a "rare disease" by the United States Office of Rare Diseases [ORD] of the National Institute of Health [NIH] and the approximate incidence is 1 in 1000,000 8 .

Case presentation
A 5-month old male Indian child with normal karyotype (46 XY) born to a 26-year-old primigravida, full term by C-section, presented with limb deformities associated with bilateral ectrodactyly of feet ( Figure 1 and Figure 2), syndactyly of right hand ( Figure 3) and ectrodactyly of left hand (Figure 4). At the medial distal third of the right femur, a large protrusion was present ( Figure 1 and Figure 5). Radiographic images showed bifid femur with fibular agenesis (Figure 6), absence of right 3, 4, 5 metatarsals and     phalanges, absence of left 4, 5 metatarsals and phalanges of foot (Figure 7), left lateral X-ray showing caudal (sacrococcygeal) agenesis (Figure 8). Initial diagnosis was made when the parents brought the child to the out-patient department concerned about limb abnormality at the age of 3 months and the final diagnosis was made following admission to the in-patient unit at 5 months, based on both clinical presentation and radiological images. There was no details prenatal history available.
The parents had documented second degree consanguinity but both did not have any significant family history. Similarly, there was no history of exposure to radiation, prenatal teratogenic medications and infections during pregnancy. The mother did not smoke or drink during pregnancy. The child was breast-fed with good appetite and   cry, without any bowel bladder problems, change in skin color or any cleft lip/palate. Echocardiography at the time of admittance revealed no congenital heart defects. The ultrasonography of abdomen and pelvis revealed no visceral or renal abnormalities. Surgical reconstruction treatment was advised but the parents did not give any consent for treatment.

Discussion
In this presenting case, the parents of the child affected by GWC have a strong documented consanguinity. To the author's knowledge, the only previously reported case of an Arab Muslim couple who came from a region where other consanguineous families with similarly affected individuals had been reported Kohn et al. in 1989 9 , and the autosomal recessive inheritance seemed evident in the case of a child described by Raas-Rothschild et al. in 1999 10 . In this case report, we report an atypical presentation of GWC with bilateral fibular agenesis and sacrococcygeal agenesis along with pathognomonic features of GWC (bifurcation of femur, syndactyly and ectrodactyly). There were no additional associated abnormalities like cleft lip/palate, tibial agenesis, visceral or cardiac anomalies seen in this patient. In the literature, there is a case reported with distal femoral duplication with fibular agenesis 11 . The best treatment option for patients with Gollop-Wolfgang syndrome is early knee disarticulation and resection of the protruded bifurcated femur, followed by fitting of a modern prosthesis 12 . This treatment was discussed with the parents of the patient at 3 months and a follow-up visit was scheduled after 2 months.
This type of skeletal dysplasia with limb deficiencies could be the result of spontaneous gene mutations and chronic exposure to a toxic substance or infectious agents that results in the disruption of normal skeletal development. History of consanguinity is strongly associated with the developments of congenital anomalies among the newborn babies; there should be pre-marital counseling to discourage and/or to avoid consanguineous marriages and prospective genetic counseling to couple married within the blood relation to prevent conception. Similarly, prenatal diagnosis is one of the appropriate preventive measures for early detection of genetic and fetal anomalies through proper antenatal screening.

Consent
Informed written consent for publication of images and clinical details was obtained from the patient's parents.
Author contributions NA, IQ, MQ, RG have performed literature review and manuscript writing. RC helped to make the diagnosis. SA, SE helped in