Acropectorovertebral Dysplasia

Description

Acropectorovertebral dysgenesis, or F syndrome, is an autosomal dominant skeletal dysplasia characterized by carpal and tarsal synostoses, syndactyly between the first and second fingers, hypodactyly and polydactyly of feet, and abnormalities of the sternum and spine (summary by Thiele et al., 2004).

Clinical Features

Grosse et al. (1969) described 8 persons in 4 generations of a kindred (of surname beginning with F) who showed a skeletal dysplasia. Male-to-male transmission was observed. The hand malformation was mainly abnormal segmentation of the first ray. The broad, short thumbs showed incipient duplication of the distal phalanx and were, to a variable degree, webbing with the index finger, which deviated radially, especially when the webbing was extensive. In some, the web contained an extra bone, which seemed to be derived from the thumb phalanges and was associated with the formation of a bony bridge between the tip of the thumb and a radial projection from the distal end of the first index phalanx. In some, the web between the first two digits was complete and the two distal phalanges of the index finger were then hypoplastic and formed part of a bone 'chain' connecting the tips of the thumb and index finger. Capitate and hamate were invariably fused; other carpals were sometimes incorporated into the fusion. The toes were also webbed, especially the first and second, and malformed. Pectoral and vertebral anomalies were sternal deformity and spina bifida occulta at L5 or S1.

Camera et al. (1995) reported on a father and daughter in a second family. Synostoses between capitate and hamate, and between talus and navicular, invariable features in the 8 affected members of the family reported by Grosse et al. (1969), were found. The hand malformation involved principally the first 2 rays. In the father and daughter, the short and malformed thumb was webbed with the index finger, which was radially deviated with duplication of the middle and distal phalanges. In the feet, polydactyly and severe metatarsal and toe anomalies were present. The father had a prominent sternum with pectus excavatum, whereas the daughter had no sternal deformity. Both of them had a mild failure of fusion of posterior arch L5 and/or S1.

Inheritance

Male-to-male transmission in the family with acropectorovertebral dysplasia reported by Grosse et al. (1969) supported autosomal dominant inheritance.

Mapping

In a study of 9 affected and 18 unaffected individuals from 4 generations of the original family reported by Grosse et al. (1969), Thiele et al. (2004) mapped the F syndrome to a 6.5-cM region on chromosome 2q36 with a maximum lod score of 4.21 for marker D2S2250. Genomic sequencing of genes in the region known to be associated with limb development showed no causative mutation.