Aase and Smith (1969) observed 2 brothers with congenital anemia and triphalangeal thumbs. Ventricular septal defect was thought to be present in 1 brother. Alter (1978), Gorlin et al. (1990), and Hurst et al. (1991) considered the syndrome ... Aase and Smith (1969) observed 2 brothers with congenital anemia and triphalangeal thumbs. Ventricular septal defect was thought to be present in 1 brother. Alter (1978), Gorlin et al. (1990), and Hurst et al. (1991) considered the syndrome reported by Aase and Smith (1969) to be the same as Blackfan-Diamond syndrome. Alter (1978) and Gorlin et al. (1990) referred to it as Aase-Smith syndrome II. Gazda et al. (2008) reviewed available medical records for 20 of the 24 RPL5 mutation-positive DBA patients and found that 14 of 20 had physical malformations, including craniofacial, thumb, and heart anomalies, and 11 of them had multiple, severe abnormalities. Thumb abnormalities were seen in 8 patients; cleft lip and/or palate or cleft soft palate was seen in 9 patients, isolated or in combination with other facial malformations, such as micrognathia, hypertelorism, or mandibular hypoplasia with retrognathia, and/or with other physical abnormalities of the heart or thumb. One patient had melanoma.
Gazda et al. (2008) screened 196 probands with Diamond-Blackfan anemia for mutations in 25 genes encoding ribosomal proteins and identified 15 different mutations in the RPL5 gene in 18 probands and 6 additional family members (see, e.g., 603634.0001-603634.0006); ... Gazda et al. (2008) screened 196 probands with Diamond-Blackfan anemia for mutations in 25 genes encoding ribosomal proteins and identified 15 different mutations in the RPL5 gene in 18 probands and 6 additional family members (see, e.g., 603634.0001-603634.0006); 3 of the mutation-positive patients were from the family with DBA originally described by Aase and Smith (1969) (see 603634.0005). The mutations segregated with disease in multiplex families and were not found in at least 150 controls. Functional studies demonstrated defects in the maturation of ribosomal RNAs associated with mutation in the RPL5 gene. Gazda et al. (2008) stated that RPL5 was the first ribosomal protein gene to be associated with cleft lip and/or cleft palate abnormalities in DBA patients, and that mutations in RPL5 appeared to cause a more severe phenotype than mutations in RPL11 (604175) or RPS19 (603474).