Autosomal recessive congenital ichthyosis of the Golden Retriever, with two molecular forms: ICH1, due to a PNPLA1 mutation, and ICH2, due to a deletion in ABHD5 (α/β-hydrolase domain-containing 5), described in 2022 in North American Golden Retrievers. Both share the ω-O-acylceramide biosynthesis pathway of the skin barrier and produce generalized scaling from birth. Genetic testing is complementary to dermatological examination.

Affected breed: Golden Retriever. ICH1 (PNPLA1) is relatively common in the breed; ICH2 (ABHD5) has been described only in North American lines and appears to be rare. Exact population frequencies by country: limited data.

- Generalized whitish or darkish scales from the first weeks of life\n- Fine to large, lamellar, adherent scales, especially on the trunk and lumbar region\n- Greasy or unkempt-looking coat in some cases\n- In ICH2, more severe and adherent scales than in ICH1 according to breeders\n- Orthokeratotic laminated/compact hyperkeratosis with hypergranulosis and mild acanthosis on histology\n- No marked inflammatory erythema (non-epidermolytic form)\n- Heterozygous dogs are clinically normal

Golden Retriever ichthyosis was described clinically in 2007-2008 (Mauldin, Credille, Casal) and characterised as a non-epidermolytic retention ichthyosis, autosomal recessive, with onset in the first weeks of life. In 2012, Grall and colleagues performed a GWAS with only 40 Golden Retrievers (20 affected and 20 controls) and mapped the locus to chromosome 12; resequencing of the candidate gene PNPLA1 revealed an indel mutation in exon 8 (c.1445_1447delinsTACTACTA, p.Asn482Ilefs*11) that introduces a premature stop codon and segregates perfectly with the disease. The canine finding allowed PNPLA1 to be identified as a new human ichthyosis gene, when mutations were found in two human families with ARCI. In 2022, Kiener and colleagues investigated 14 Golden Retrievers with ichthyosis that did not carry the PNPLA1 variant: whole-genome resequencing and segregation in a large family identified a 14 base-pair deletion in exon 7 of ABHD5 (c.1006_1019del, p.Asp336Serfs*6), which alters the last 14 codons of the α/β-hydrolase domain and is responsible for a new form proposed to be named ICH2. The variant was found only in North American Golden Retrievers.

- Test Golden Retriever breeding animals with a combined PNPLA1 + ABHD5 panel before mating, especially if they are of North American ancestry\n- Do not mate two carriers of the same variant: 25 % risk of affected homozygotes in each litter\n- A valuable carrier can be mated to a clear animal; offspring intended for breeding must be tested and, ideally, the carrier progressively replaced by clear descendants, without narrowing the gene pool (important in breeds with high frequency such as the Golden Retriever for ICH1)\n- Exclude from breeding animals that are homozygous affected for either of the two variants\n- In Golden Retrievers with generalized scaling since suckling, request a combined PNPLA1+ABHD5 test before any mating of the parents\n- Communicate the status to the buyer and record the result in the pedigree; remember that a dog "clear" for ICH1 may be a carrier of ICH2, so the full panel is preferable to the single PNPLA1 test

Differential diagnosis with other canine ichthyoses (SLC27A4 in the Great Dane, NIPAL4 in the American Bulldog, KRT10 in the Norfolk Terrier, TGM1 in the Jack Russell Terrier), with atopic dermatitis (usually pruritic and of later onset, whereas congenital ichthyosis is usually non-itchy), primary seborrhoea, demodicosis and endocrinopathies. Biopsy with electron microscopy (when available) shows alterations in the lipid barrier. Management is palliative: emollients, keratolytic baths (salicylic acid, urea) and control of secondary infections. Genetic testing is the key tool for breeding advice in a breed with a very high carrier frequency for ICH1.

1. Grall A et al. 2012, mutaciones de PNPLA1 causan ictiosis congénita autosómica recesiva en Golden retriever y humanos (PMID 22246504)
2. Kiener S et al. 2022, deleción con cambio de marco en ABHD5 en Golden Retrievers con ictiosis (PMID 34791225)
3. OMIA:001588 Ictiosis congénita (PNPLA1) del Golden retriever