Orel (1928) and Holmes et al. (1972) described fusion of the fourth and fifth metacarpals as an X-linked recessive trait. Other reports are more consistent with autosomal dominant inheritance (e.g., Habighorst and Albers, 1965). The families of Lerch ... Orel (1928) and Holmes et al. (1972) described fusion of the fourth and fifth metacarpals as an X-linked recessive trait. Other reports are more consistent with autosomal dominant inheritance (e.g., Habighorst and Albers, 1965). The families of Lerch (1948) and of Habighorst and Albers (1965) suggested autosomal dominant inheritance because of affected females and male-to-male transmission. Anneren and Amilon (1994) described this malformation in 5 males in 4 generations of a family. The carrier females were normal by clinical and radiologic examination. Holmes et al. (1972) excluded linkage of the disorder in their family to the colorblindness locus on Xq28. An X-linked form of split-hand/foot malformation (SHFM2; 313350) has been mapped to Xq26. The possibility of allelism of X-linked ectrodactyly and X-linked metacarpal fusion should be investigated. Lonardo et al. (2004) described a 4-generation family with isolated fusion of the fourth and fifth metacarpals. They noted that only males were affected and that there were no instances of male-to-male transmission, consistent with X-linked recessive transmission. Jamsheer et al. (2013) described a 12-year-old Polish boy in whom ulnar deviation of both fifth fingers was noted at birth. He was also found to have right-sided inguinal hernia and hydrocele of testis. Radiography showed fusion of the fourth and fifth metacarpals and shortening of the fifth metacarpal bones. On examination at 12 years of age, he had normal stature, with bilateral shortening of the fifth rays of the hands as well as minimal syndactyly of toes 2-3. He had a triangular face, with upslanted palpebral fissures and a thin upper lip, but no additional dysmorphic features were noted. Intellectual development was normal, although he had attention deficit-hyperactivity disorder. He had 2 younger brothers who were clinically and radiologically normal. Jamsheer et al. (2013) also studied a German boy with isolated bilateral metarcarpal 4-5 fusion with shortening of the fifth metacarpals.
In a 12-year-old Polish boy with metacarpal 4-5 fusion who was negative for mutation in the NOG (602991), GDF5 (601146), and HOXD13 (142989) genes, Jamsheer et al. (2013) performed whole-exome sequencing and identified a nonsense mutation in the ... In a 12-year-old Polish boy with metacarpal 4-5 fusion who was negative for mutation in the NOG (602991), GDF5 (601146), and HOXD13 (142989) genes, Jamsheer et al. (2013) performed whole-exome sequencing and identified a nonsense mutation in the FGF16 gene (R179X; 300827.0001). The mutation was present in heterozygosity in his clinically and radiologically unaffected mother, but was not found in his unaffected brothers. Sequencing of the FGF16 gene in a German boy with typical metacarpal 4-5 fusion revealed another nonsense mutation (S157X; 300827.0002); his parents were unavailable for study.