Coloboma Of Macula With Type B Brachydactyly

Sorsby (1935) described a mother and 5 children with bilateral pigmented macular coloboma and brachydactyly. One of the patients had unilateral absent kidney. Two other children and the father were unaffected. The skeletal defect was of the type described by MacArthur and McCullough (1932) as apical dystrophy with macular dystrophy and classified here as brachydactyly, type B (113000). Abnormalities are confined to the distal two phalanges. The distal phalanx may be completely absent. The distal phalanx of the thumb is usually broad or bifid. The brother and sister reported by Phillips and Griffiths (1969) in some ways resemble the patients of Sorsby. Smith et al. (1980) described a patient with severe short-limbed dwarfism and macular coloboma. Histologic changes in cartilage resembled somewhat those of diastrophic dwarfism; the chondrocytes were surrounded by a corona of densely staining material. However, some other histologic and clinical features of diastrophic dwarfism were not present.

Thompson and Baraitser (1988) reported a further generation of Sorsby's original family. The proband was a 7-year-old boy referred to the genetics clinic because of deafness. The thumbs were bifid, there was aplasia or hypoplasia of the nails, and partial syndactyly between digits 3 and 4 on the left hand. The feet showed large halluces, abnormal nails, and syndactyly between the fourth and fifth toes bilaterally. Ears were protuberant, more marked on the right side. His 8-year-old brother had nearly identical anomalies of the hands and feet. Both children had congenital pigmented colobomas of both maculars associated with nystagmus and reduced visual acuity. The 7-year-old had no renal anomaly; no kidney was demonstrated on the left by intravenous pyelogram in the older brother. The younger brother had bilateral sensorineural hearing loss of 70 to 80 dB, worse at high frequencies; the older brother had normal hearing. The mother had absent right kidney and ureter, as well as uterus didelphys (double uterus) and double vagina. (The authors stated that the duplication of the uterus and vagina in the mother may or may not be part of the syndrome.) With the information added by Thompson and Baraitser (1988), the total number of affected members of the family, in 4 generations, was 9.

Bacchelli et al. (2003) recontacted 1 affected member of the family reported by Sorsby (1935) and Thompson and Baraitser (1988) and also ascertained a sporadic case with a combination of type B brachydactyly, left choroidal coloboma, and oligodontia. Direct sequencing of the entire coding region of the ROR2 (602337) gene, which is affected in brachydactyly type B1, revealed no mutation in either the familial or the sporadic case. A mutation in a regulatory region could not be excluded because those regions had not been characterized at the time of the study.