Acrofrontofacionasal Dysostosis 1

Clinical Features

Richieri-Costa et al. (1985) described an apparently 'new' autosomal recessive MCA/MR syndrome in a boy and girl, offspring of first-cousin parents. Both had mental retardation, short stature, hypertelorism, broad notched nasal tip, cleft lip/palate, postaxial camptobrachypolysyndactyly, fibular hypoplasia, and anomalies of foot structure. Richieri-Costa et al. (1992) reported another Brazilian family in which a woman had characteristic features; her similarly affected brother died at age 1 year.

Guion-Almeida and Richieri-Costa (2003) reported a third Brazilian family with acrofrontofacionasal dysostosis in a brother and sister born of second-cousin parents.

Prontera et al. (2011) described 2 Indian sisters with a multiple congenital anomalies/intellectual disability syndrome consistent with AFFND1. At birth, the proband showed bilateral cleft lip/palate, minor facial anomalies, bilateral complete syndactyly of the third and fourth digits, and clubfeet. In the first month of life, she was found to have mixed hearing loss, atrophy of the optic nerves, and anomalies on electroencephalography. X-rays revealed hypomineralization of the calvaria, large anterior fontanel, dislocation of hips, short long bones, brachymetacarpia, hypoplastic distal phalanges, polysyndactyly (an extra digit between digits 3 and 4), and hypoplastic fibulae. Examination at 11 years of age showed global microsomia, with height, weight, and head circumference all below the third percentile. She had profound mental retardation and was unable to walk or talk. Dysmorphic features included brachycephaly, wide forehead, hypertelorism, ptosis, wide nasal bridge with broad and notched nasal tip, oligodontia, hypoplastic gums, wide and protruding upper central incisors, and downturned ears with wide conchae, thin helices, and absent lobules. She also exhibited diffuse muscular hypotrophy, scoliosis, 4-limb mesomelia, broad and proximally placed thumbs, camptodactyly and clinodactyly of the fifth digits, short third through fifth metatarsals, overlapping toes, and hypoplastic second and third toes. Her affected younger sister had an overlapping phenotype without polysyndactyly. MRI in the older sister was normal; in the younger sister, it showed a thin corpus callosum.

Inheritance

The occurrence of this syndrome in sibs and in consanguineous families suggests autosomal recessive inheritance (Guion-Almeida and Richieri-Costa, 2003).