Hereditary syndrome of the Nova Scotia Duck Tolling Retriever that combines cleft lip and/or palate with syndactyly (cutaneous and/or bony fusion of the third and fourth digits). It is caused by a frameshift deletion in ADAMTS20 that alters craniofacial and limb development during embryogenesis. The signs are present from birth and inheritance is autosomal recessive.

Nova Scotia Duck Tolling Retriever. The 13 CLPS cases in the original study were homozygous for the deletion and several parents were carriers, consistent with recessive inheritance. The true population frequency of ADAMTS20 deletion carriers in the breed is not well characterised (limited data); the figure of 'one third heterozygotes' appearing in the literature refers to a synonymous variant of PUS7L, not to ADAMTS20.

- Cleft lip and/or palate, with or without neonatal nutritional compromise\n- Complete or partial simple syndactyly of the third and fourth digits (soft tissue and/or bone)\n- Possible associated dental abnormalities\n- Condition present from birth

Wolf et al. (2015) described the complex phenotype of cleft lip/palate and syndactyly (CLPS) in 13 NSDTR dogs and, using GWAS and sequencing, identified a two-base-pair deletion in ADAMTS20 (CFA27) that segregates with the disease. The same study found a signal in humans for ADAMTS20 variants in cleft lip and palate, reinforcing its role in development. The molecular test was incorporated into the breed's breeding schemes.

- Genotype breeding animals before mating.\n- Do not mate two carriers (25 % affected homozygotes).\n- Mate carriers with clear homozygotes and keep only the clear offspring for breeding.\n- Exclude affected homozygotes from breeding.\n- Given the recessive nature, genotype-based selection makes it possible to eliminate affected animals without giving up breed diversity.

Neonatal management of cleft palate may require tube feeding and/or reconstructive surgery; syndactyly is usually managed surgically on an optional basis. Before attributing the condition to ADAMTS20, rule out other causes of oral clefting, such as the DLX6-linked form of cleft palate (OMIA001919-9615), also described in the NSDTR.

1. Wolf ZT et al. 2015. Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate. PLOS Genetics. PMID: 25798845
2. Dubail J, Apte SS. 2015. Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics. Matrix Biology. PMID: 25770910
3. OMIA:001140-9615. Cleft lip with or without cleft palate, ADAMTS20-related in Canis lupus familiaris. Online Mendelian Inheritance in Animals.