Expanded breed panel of the cavalier King Charles spaniel combining five hereditary conditions: X-linked muscular dystrophy due to dystrophin defect (MD, canine model of Duchenne), episodic falling (EF, hypertonic crises), macrothrombocytopenia (MTC, macroplatelets and asymptomatic thrombocytopenia), degenerative myelopathy (DM, SOD1 exon 2 variant) and dry eye curly coat syndrome (CCS, dry eye + curly coat + ichthyosis). The panel allows a joint breeding strategy for several conditions prevalent in the breed.

Cavalier King Charles spaniel. MD of the CKCS has a low prevalence and is associated with a founder mutation; there are no consolidated carrier figures in the accessible literature. For EF, CCS and MTC the carrier frequency in the accessible literature is limited. DM exon 2 has a low frequency in the breed (limited data).

- MD: progressive muscle weakness from puppyhood, hypertrophy of the lingual/cervical musculature, abnormal gait, lordosis; severe course\n- EF: hypertonic episodes with stiffness and falling induced by exercise/emotion\n- MTC: macroplatelets and asymptomatic thrombocytopenia; possible interference with haematology\n- DM: ataxia and paresis of the pelvic limbs in the adult, progression to paraplegia\n- CCS: congenital keratoconjunctivitis sicca, curly coat, ichthyosis

Muscular dystrophy of the CKCS was associated with a mutation in the dystrophin gene (DMD) in the hot-spot region exon 50/intron 50 (Walmsley et al., 2010, PLoS ONE), a model of human Duchenne. EF and CCS were attributed to a deletion in BCAN and a variant in FAM83H respectively (Forman et al., 2012). MTC of the CKCS was associated with a variant in TUBB1. DM exon 2 of SOD1 is included because of its pan-breed nature. The accessible literature does not allow all frequencies to be specified for the CKCS.

- Genotype breeding females for DMD before mating and affected males are not used\n- Genotype breeding dogs for BCAN, TUBB1, SOD1 exon 2 and FAM83H before mating\n- For the recessive ones: do not cross two carriers of the same variant; a carrier may be crossed with a clear animal and the offspring intended for breeding must be tested\n- For X-linked MD: a carrier female produces 50% carrier daughters and 50% affected sons if crossed with a clear male\n- After a confirmed case, do not repeat the parental cross and communicate the status to the buyer

MTC of the CKCS can distort platelet counts by analyser: confirm with smear and manual count. MD of the CKCS must be distinguished from other congenital myopathies and from sarcoglycanopathies. EF and CCS are clinical+genetic diagnoses: the episodic hypertonic picture and the triad dry eye + curly coat + ichthyosis are suggestive. DM in the CKCS is uncommon and should be considered only after ruling out compressive/structural causes.

1. Walmsley GL et al. 2010, mutación hot-spot del gen de la distrofina en cavalier King Charles spaniels deficientes en distrofina. PLoS One. PMID: 20072625
2. Forman OP et al. 2012, mapeo paralelo y secuenciación simultánea: deleciones en BCAN y FAM83H. PLoS Genet. PMID: 22253609
3. Gill JL et al. 2012, microdeleción de BCAN asociada al episodic falling. Neurobiol Dis. PMID: 21821125
4. Davis B et al. 2008, mutación en beta1-tubulina y macrotrombocitopenia en cavalier King Charles spaniels. J Vet Intern Med. PMID: 18466252
5. Awano T et al. 2009, mutación de SOD1 en la mielopatía degenerativa canina. Proc Natl Acad Sci U S A. PMID: 19188595