Hereditary pituitary dwarfism of the German Shepherd and related breeds, caused by combined deficiency of pituitary hormones (GH, TSH, gonadal hormones) due to mutations in LHX3. Puppies are born normal but reduce their growth rate; they present reduced stature, persistent puppy coat with symmetrical alopecia of the trunk and neck, hyperpigmentation and, in some cases, neurological signs due to atlantoaxial malformation.

Pituitary dwarfism due to LHX3 documented in German Shepherd, Saarloos, Czechoslovakian Wolfdog, Tibetan Terrier and White Swiss Shepherd. The Finnish Lapphund is EXCLUDED: its pituitary dwarfism is due to a variant in POU1F1 (OMIA002315-9615).

- Normal growth in the first weeks, with marked subsequent slowing
- Proportionate reduced stature (dwarfism)
- Retention of the puppy coat and absence of guard hair
- Bilateral symmetrical alopecia on the trunk, neck and proximal limbs
- Hyperpigmentation, seborrhoea and secondary pyoderma
- Deficiency of GH, TSH and reproductive hormones; lethargy
- Neurological signs due to atlantoaxial malformation/instability in some cases

Pituitary dwarfism in the German Shepherd was known since the 1980s as a combined pituitary hormone deficiency with autosomal recessive inheritance. Voorbij et al. (2011) mapped the defect to canine chromosome 9 and demonstrated that a contraction of a 7-bp repeat in intron 5 of LHX3 causes aberrant splicing (skipping of exon 5 or retention of intron 5). In the same work they described, in a compound heterozygous dwarf, a second variant (ACA duplication in exon 5). Voorbij et al. (2014) confirmed the deletion in the Saarloos Wolfdog and the Czechoslovakian Wolfdog, and Thaiwong et al. (2021) in the Tibetan Terrier.

- Test breeding animals of the affected breeds (German Shepherd, Saarloos, Czechoslovakian, Tibetan Terrier, White Swiss Shepherd) before breeding
- Do not mate two carriers: 25% affected homozygous offspring
- Carriers may be mated with clear animals; test offspring intended for breeding
- Prioritise genotyping of the intron 5 deletion (main variant)
- Record the results with the breed club to reduce the allele frequency

Pituitary dwarfism must be differentiated from other causes of reduced stature (isolated GH deficiency due to GH1, disproportionate dwarfism due to PCYT1A in Vizslas, hypothyroidism, malnutrition). Diagnosis relies on clinical findings, the hormone profile (GH/IGF-1, TSH, sex hormones) and, definitively, on the LHX3 DNA test. The intron 5 variant is the common cause in the German Shepherd and related breeds; the c.545_547dup duplication has been described only in compound heterozygosity.

1. Voorbij AM et al. 2011. A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and pituitary dwarfism in German shepherd dogs. PLoS One. PMID: 22132174
2. Voorbij AM et al. 2014. Pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs is associated with a mutation in LHX3. J Vet Intern Med. PMID: 25273400
3. Thaiwong T et al. 2021. Dwarfism in Tibetan Terrier dogs with an LHX3 mutation. J Vet Diagn Invest. PMID: 33890524
4. Kyöstilä K et al. 2021. Intronic variant in POU1F1 associated with canine pituitary dwarfism. Hum Genet. PMID: 33550451
5. Schils G et al. 2025. Pituitary Dwarfism and Adrenocorticotropic Hormone Deficiency in a White Swiss Shepherd Dog With LHX3 Mutation. J Vet Intern Med. PMID: 40833232
OMIA002314-9615.