Fibular Aplasia Or Hypoplasia, Femoral Bowing And Poly-, Syn-, And Oligodactyly

A number sign (#) is used with this entry because of evidence that Fuhrmann syndrome is caused by homozygous mutation in the WNT7A gene (601570) on chromosome 3p25.

Clinical Features

In 2 boys and a girl of a Turkish-Arabian family working in Germany, Fuhrmann et al. (1980) described a 'new' syndrome consisting of bowing of the femurs, aplasia or hypoplasia of the fibula, and poly-, syn-, and oligodactyly. Parental consanguinity was denied. However, both parents belonged to the same Christian minority from the same province. Other findings included hypoplasia of pelvis, congenital dislocation of hips, absence or coalescence of tarsal bones, absence of various metatarsals, hypoplasia of fingers and fingernails, and postaxial polydactyly. The bowing of the femurs looked like that of camptomelia. Fuhrmann et al. (1982) provided follow-up, including the prenatal diagnosis of a fourth affected sib and the anatomic findings in the abortus.

In a male and female offspring of Turkish parents related as cousins once removed, Pfeiffer et al. (1988) observed a lethal syndrome consisting of absence of the fibula and ulna with oligodactyly, joint contractures, right-angle bowing of the femurs, cleft lip and palate, and, in the sib examined, an Arnold-Chiari anomaly with communicating hydrocephalus, caudally displaced cerebellum with absence of the velum medullare and of the posterior vermis, and focal microgyria in the frontal area. The first infant was delivered at 28 weeks by cesarean section because of premature labor and lived only a short period. The upper lip appeared attached to the nose because the tongue was squeezed into the cleft lip. The abnormalities in the second affected child were detected at 20 weeks of the pregnancy by ultrasonography and the pregnancy was terminated. The patients of Fuhrmann et al. (1980) and Pfeiffer et al. (1988) came from different parts of Turkey. Lipson et al. (1991) reported 2 unrelated cases, 1 from a consanguineous Vietnamese family and the second from a nonconsanguineous Polish family.

In an extensive and highly inbred Muslim family from Pakistan, Kumar et al. (1997) described 4 children with a similar pattern of skeletal abnormalities, including aplasia/hypoplasia of the ulnas, hypoplasia of the pelvis, aplasia/hypoplasia of the femurs, fibular aplasia, and variable digital abnormalities, as well as absent/dysplastic nails. Overlap was recognized with Fuhrmann syndrome and with the Al-Awadi/Raas-Rothschild syndrome (276820). It also had similarities to the femur-fibula-ulna syndrome, or FFU syndrome (228200).

Woods et al. (2006) analyzed the Pakistani Muslim family described by Kumar et al. (1997). Two further affected individuals had been born who conformed to the original phenotype. In the upper limbs hypoplasia/aplasia of the ulnar rays was identified, which was accompanied by shortening and bowing of the radius. The fifth digits were hypoplastic but all other elements were present. There was hypoplasia of the nails with a radial-ulnar gradient; the thumbs were the most severely affected, with complete absence of the nails. The pelvis was highly abnormal, with hypoplastic iliac wings and, in 1 case, absent os ischii. The patellae were absent and in 1 subject the knee joints were fused. There was complete absence of the toenails and loss of individual toes. In each affected person limb involvement was symmetrical, legs were more affected than arms, and the functional deficit was far greater than that expected because of limb shortening alone.

Aynaci et al. (2001) described a single case of presumed Fuhrmann syndrome in a male newborn in a consanguineous Turkish family.

Huber et al. (2003) described 2 unrelated boys with bilateral fibular aplasia, poly- and oligodactyly, and bowed tibiae in 2 nonconsanguineous Brazilian families. These cases were similar to those reported by Fuhrmann et al. (1980) and supported the view that this entity is a distinct combination of developmental limb anomalies.

Molecular Genetics

In the Pakistani Muslim family described by Kumar et al. (1997), Woods et al. (2006) found that affected individuals had 3 homozygous changes, all in exon 3 of the WNT7A gene: a missense mutation, 630G-A, that led to an alanine-to-threonine substitution (A109T; 601570.0002), and 2 known synonymous SNPs.

History

Vogel (1997) provided an obituary of Walter Fuhrmann (1924-1995), who was Professor of Human Genetics at Giessen University in Germany from 1967 until 1992.