Recessive disease of the Dachshund (described in the smooth-haired miniature) that combines coat colour dilution with severe neurological deficit, analogous to human Griscelli syndrome type 1. Puppies show a light coat from birth and, in the first weeks, an inability to hold the head upright and to adopt stable postures. The progression is severe and leads to early euthanasia. It is distinct from the isolated 'd' colour dilution due to MLPH, which is not associated with neurological signs.

CDN due to MYO5A documented ONLY in the miniature Dachshund (one puppy, Christen 2021). Do NOT use for D-locus d1 of other breeds (use dlph/MLPH).

- Diluted coat colour from birth\n- Inability to hold the head upright\n- Postural instability and inability to maintain a stable prone position\n- Palpable tension in the neck and shoulders without real support\n- Histology with melanin accumulation in follicles and dermal pigmentary cells\n- No macroscopic lesions of the CNS

Christen and colleagues (2021) studied a female smooth-haired miniature Dachshund puppy with colour dilution and severe neurological defects. Histopathological study revealed melanin accumulation in the follicles and dermal pigmentary cells, comparable to that described in MLPH dilution. Whole-genome sequencing against 795 controls revealed a private frameshift variant in MYO5A (c.4973_4974insA; p.Asn1658Lysfs*28), which truncated the cargo-binding globular domain of myosin VA. The variant co-segregated with the phenotype in the index family and was not found in 142 unrelated Dachshunds. MYO5A causes Griscelli type 1 in humans and 'lavender foal' in horses.

- In a puppy with diluted coat and neurological signs, suspect CDN and confirm by MYO5A genetic test if available\n- Do not mate two confirmed carriers: 25% risk of affected homozygotes\n- A carrier can be mated to a clear dog; offspring intended for breeding should be tested\n- Distinguish from 'd' colour dilution due to MLPH (isolated phenotype, without neurological signs)\n- Consider the rarity of the mutation: in most Dachshunds with diluted coat the cause will be MLPH, not MYO5A

The main differential diagnosis is MLPH colour dilution (d1, d2, d3 alleles), which is NOT associated with neurological defects and predisposes to colour dilution alopecia (CDA). CDN should be suspected when a diluted puppy presents ataxia or cervical hypotonia. Skin histology is similar to MLPH, but the neurological picture differs. MYO5A is an essential intracellular transporter in melanocytes and Purkinje dendrites; its loss explains the pigmentation and cerebellar dysfunction. In humans, Griscelli syndrome type 1 combines partial albinism with primary neurological deficit.

1. Christen M, de le Roi M, Jagannathan V, Becker K, Leeb T. MYO5A frameshift variant in a miniature Dachshund with coat color dilution and neurological defects resembling human Griscelli syndrome type 1. Genes (Basel) 12(10), 2021. PMID: 34680875
2. OMIA:001501-9615. Dilute coat color with neurological defects in Canis lupus familiaris. https://omia.org/OMIA001501/9615/