Test Detail

Pituitary Dwarfism (pituitary form)

Hormonal · Dog

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.

Inheritance pattern	Autosomal recessive
Gene / Mutation	Two causal variants in LHX3 (OMIA002314-9615): (1) main variant, a 7-bp deletion in intron 5 that reduces the intron to 68 bp (g.50129168_50129174del; c.621+21_621+27del), with aberrant splicing (skipping of exon 5 or retention of intron 5); present in German Shepherd, Saarloos, Czechoslovakian Wolfdog, Tibetan Terrier and White Swiss Shepherd. (2) second variant, in-frame duplication c.545_547dup p.(Asn182dup) (g.49252491_49252493dup), described in a compound heterozygous dwarf.
Penetrance	Homozygotes for the intron 5 deletion show the complete phenotype (combined pituitary hormone deficiency and proportionate dwarfism); heterozygotes are clinically normal carriers. No reduced penetrance is described. Carrier frequency of the deletion among healthy animals: 9.4% in Dutch German Shepherd, 31% in Saarloos and 21% in Czechoslovakian Wolfdog.
Code	kwdz
Turnaround time	15 days
Price	52,60 €

Incidence

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).

Breeder management

- 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

Specialist notes

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.

References

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.

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