A pair of sibs with tibial hemimelia born to phenotypically normal parents

Abstract

Tibial hemimelia is a rare congenital anomaly characterized by deficiency of the tibia with relatively intact fibula. Tibial hemimelia is identified as a solitary disorder, or a part of more complex malformation syndromes. Although the majority of cases with tibial hemimelia are sporadic, affected families with possible autosomal dominant or autosomal recessive inheritance have been reported. Here we report a pair of sibs, 6-and 2-year-old Japanese boys, with tibial hemimelia born to unrelated, phenotypically normal parents. The type of tibial hemimelia and associated malformations of hands and feet was quite different between the brothers. The elder brother was compatible with the Gollop-Wolfgang complex, and the younger brother with tibial agenesisectrodactyly syndrome. Screening of mutation by direct sequencing of candidate genes including Sonic hedgehog, HOXD-11, and HOXD-12 was unable to identify a disease-causing mutation.

Bilateral tibial hemimelia type 1 (1a and 1b) with T9 and T10 hemivertebrae: a novel association

“…However, if this was just a random occurrence, the probability would be one in a billion (tibial hemimelia frequency 1 = 1/1,000,000 x hemivertebrae frequency 7 = 1/1000 Tibial hemimelia may also constitute a part of a malformation complex or syndrome such as the Gollop-Wolfgang complex and tibial agenesis-ectrodactyly, triphalangeal thumbpolysyndactyly, tibial hemimelia/split-hand/split-foot and Langer-Giedion syndromes. 2,8,9 In our case, the previous workup with full ultrasonography and X-ray body scan ruled out malformations that had previously been associated with this disorder.…”

“…1 Tibial hemimelia is mostly sporadic and can be identified as an isolated disorder or as part of malformation syndromes. 2 Based on the radiographic appearance, four types of tibial hemimelia have been recognized: type 1a, with absent tibia and hypoplastic lower femoral epiphysis; type 1b, with absent tibia but normal lower femoral epiphysis; type 2, in which the tibia is distally deficient and well developed proximally; type 3, in which the tibia is proximally deficient and well ossified distally; and type 4, characterized by shortening of the distal tibia, with distal tibiofibular diastasis and normally developed proximal tibia. 3 Patients with this longitudinal deficiency of the lower limb have unique clinical findings that vary in severity and are associated with a wide range of congenital anomalies.…”

Bifurcation of the femur with tibial agenesis and additional anomalies

“…Endo et al [1998] found only 12 cases in the literature and added a new case. The term Gollop-Wolfgang complex is also used in patients with bifid femur and tibial agenesis but without hand ectrodactyly, as in our second patient [Evans and Chudley, 1999;Raas-Rothschild et al, 1999;Matsuyama et al, 2003]. Bifurcation of the femur with tibial agenesis and ectrodactyly has also been described in tibial agenesis-ectrodactyly syndrome [OMIM # 119100], which consists of major anomalies as tibial agenesis, hand or foot ectrodactyly, ulnar defects, femoral defects, and minor anomalies as aplasia of patellae, hypoplasia of the hallux, polydactyly, and cup ears.…”

“…Familial cases of Gollop-Wolfgang complex have also been reported. The pedigrees reported by Gollop et al [1980] and Wolfgang [1984] could be compatible with autosomal dominant inheritance with reduced penetrance, as in tibial agenesis-ectrodactyly syndrome but the reports of affected sibs and affected offspring of consanguineous matings [Richieri-Costa et al, 1987a;Kohn et al, 1989;Majewski et al, 1996;Raas-Rothschild et al, 1999;Yetkin et al, 2001;Matsuyama et al, 2003] suggests autosomal recessive inheritance. This apparent discrepancy could be explained by genetic heterogeneity, but Lurie and Ilyina [1986] suggested a two-gene hypothesis comprising an epistatic recessive gene controlling the expression of a dominant gene responsible for the predisposition to this anomaly.…”

A Case of Bilateral Tibial Hemimelia Type IV and V with Bilateral Subdural Hygroma and Atrial Septal Defect

“…2 The defect could be either complete or incomplete, and occurs either as a solitary disorder, or as a part of more complex malformation syndrome. 1,3 Associated abnormalities include those of the musculoskeletal system of both lower and upper limbs, orofacial part, urogenital and cardiovascular systems. The tibial reduction defects were initially classified into four major types based only on X-ray…”