Crane-Heise Syndrome

Clinical Features

Gorlin et al. (1990) used the designation Crane-Heise syndrome for a severe lethal syndrome observed in 3 sibs, 2 of whom were female, by Crane and Heise (1981). The first-born sib showed disproportionately large head with small face, depressed nasal bridge with anteverted nares, micrognathia, apparent ocular hypertelorism, low-set and posteriorly rotated ears with hypoplastic helix, short neck, partial soft tissue syndactyly of the fingers and toes involving interdigital spaces 2 to 4, and bilateral talipes equinovarus. The infant died at 2 weeks of age. Distinctive radiologic features included absence of cervical vertebrae and clavicles and hypoplastic scapulas, as well as very poorly mineralized calvarium, leading to a prenatal diagnosis of anencephaly. The first affected sib was delivered at term and was small for gestational age. The diagnosis in the 2 later sibs was made prenatally by ultrasonography. The second-born affected sib died 2 days after birth. The parents elected to terminate the third affected pregnancy at 17 weeks' gestation. Gorlin (1994) knew of another unpublished case.

Characteristic features of the Crane-Heise syndrome include poorly mineralized calvaria and clavicular hypoplasia, facial anomalies with severe micrognathia and cleft palate, hypertelorism, and broad and wide nostrils. Some of the features resemble those of the aminopterin syndrome sine aminopterin (600325), leading Barnicoat et al. (1994) to suggest that they represent part of a spectrum of severity that includes these 2 conditions.

Zand et al. (2003) described a family in which 2 sibs showed features strikingly similar to those presented by Crane and Heise (1981), as well as distinct clinical differences, including distal phalangeal hypoplasia and mild cardiac and gastrointestinal abnormalities. No cytogenetic, molecular, or biochemical findings helped elucidate the basis of this rare phenotype.