By: Tuddow Thaiwong DVM, PhD, DACVP; Sarah Corner DVM, PhD, DACVP | Academic Specialist, Anatomic Pathology

Recently, MSU VDL veterinary pathologists discovered a mutation associated with pituitary dwarfism in a group of Tibetan Terrier dogs after a blood sample from a dog showing typical clinical signs was submitted to the MSU Veterinary Diagnostic Laboratory for genetic testing. The mutation had not been identified in the breed previously. The Tibetan Terriers suspected to have pituitary dwarfism were significantly smaller than littermates, retained an immature hair coat, and developed severe hair loss.

Pituitary dwarfism is an inherited, autosomal recessive condition that leads to dwarfism due to inadequate production of growth hormone. Affected dogs appear normal at birth, however, clinical signs develop over weeks to months that include small body size compared to littermates, lack of adult hair coat, hair loss, darkening of the skin, delayed eruption or absence of permanent teeth, a shrill bark, absence of heat, and sometimes infertility in both genders.

The mutation responsible for pituitary dwarfism had been identified previously in the LHX3 gene in the German shepherd, White Shepherd, Karelian Bear dog, Saarloos Wolfdog, and the Czechoslovakian Wolfdog. A dog carrying two copies of the mutated gene is most likely to develop the disease. Carriers of one copy of the mutation do not develop clinical signs; however, breeding two carriers will transmit the mutation to about 50% of their progeny and 25% of offspring are likely to be affected.

Until the MSU VDL discovered the same LHX3 mutation in a Tibetan Terrier dog from a blood sample submitted for genetic testing, the cause of pituitary dwarfism in Tibetan Terriers had been unknown. After this initial discovery, the mutation was confirmed in Tibetan Terriers from three biologically related litters that also showed signs of pituitary dwarfism.

The MSU VDL analyzed 31 Tibetan Terriers, including the parents of all 3 dwarfs and some of their grandparents. We found 13 of 31 (42%) dogs, including all of the parents of the 3 dwarfs, were carriers (heterozygotes) of the mutation. This finding confirmed transmission of the disease in an autosomal recessive manner in Tibetan Terriers.

The discovery of the LHX3 mutation in this breed will be helpful in screening dogs that carry this mutation so that breeders can make informed decisions and eventually eliminate this trait from Tibetan Terriers. This discovery was published recently in the Journal of Veterinary Diagnostic Investigation. The Pituitary Dwarfism LHX3 mutation test is one of dozens of genetic test offerings in dogs, cats, and sheep available at the MSU VDL. This test can be ordered as an individual test or as a part of Tibetan terrier breed-specific health screening panel which includes degenerative myelopathy, progressive retinopathy - PRA3, progressive retinopathy - rcd4, pituitary dwarfism, neural ceroid lipofuscinosis, and primary lens luxation.

We hold significant hope that owners and breeders, armed with this new information, may create disease-controlled breeding plans that will ultimately lead to the reduction and possible elimination of these traits from their populations. This strategy will result in healthier breeds for generations to come.

For more information on genetic tests currently available, including sample collection and shipping details, access our online test catalog and search using keyword “genetic.” Click on test names for more information. Please contact the Laboratory with questions about testing for Tibetan Terriers, other genetic test offerings, or to request a copy of the journal articles listed below.

• Centronuclear Myopathy PCR (80326)
• CKCSID PCR (80354)
• Dermatofibrosis and Renal Tumor PCR (80343)
• Dystrophic Epidermolysis Bullosa PCR (80327)
• Epidermolytic Hyperkeratosis PCR (80355)
• Episodic Falling Syndrome PCR (80356)
• Exercise-Induced Collapse PCR (80345)
• Factor 7 Deficiency PCR (80349)
• Feline Pyruvate Kinase Deficiency PCR (80328)
• Hereditary Cataract PCR (80350)
• Hypertrophic Cardiomyopathy Maine Coon PCR (80329)
• Hypertrophic Cardiomyopathy Ragdoll PCR (80330)
• Hyperuricosuria PCR (80331)
• Ichthyosis PCR (80332)
• Junctional Epidermolysis Bullosa PCR (80344)
• Late Onset Ataxia PCR (80333)
• Malignant Hyperthermia PCR (80357)
• MDR-1 mutation PCR (80318)
• Musladin-Lueke Syndrome PCR (80358)
• Narcolepsy in Doberman Pincher PCR (80360)
• Narcolepsy in Labrador Retrievers PCR (80359)
• Neonatal Encephalopathy with Seizures PCR (80348)
• Neuronal Ceroid lipofuscinosis PCR (80334)
• Obesity PCR (80346)
• Persistent Mullerian Duct Syndrome PCR (80347)
• Pituitary Dwarfism PCR (80335)
• Polycystic Kidney Disease PCR (80336)
• Primary Lens Luxation PCR (80337)
• Progressive Retinal Atrophy Golden Retriever PCR (80338)
• Progressive Retinal Atrophy PRCD PCR (80339)
• Shar Pei Autoinflammatory Disease PCR (80361)
• Skeletal Dysplasia PCR (80342)
• SOD-1A mutation PCR (80321)
• SOD-1B mutation PCR (80320)
• Spinal Muscular Atrophy PCR (80341)
• Spinocerebellar Ataxia PCR (80340)
• Tibetan Genetic Panel PCR (80366)
• Tibetan PRA rcd4 PCR (80364)
• Von Willebrand’s Disease Type 1-B PCR (80315)
• Von Willebrand’s Disease Type 2 PCR (80319)
• Von Willebrand’s Disease Type 3-A PCR (80316)
• Von Willebrand’s Disease Type 3-B PCR (80317)

Voorbij AM, van Steenbeek FG, Vos-Loohuis M, et al. A contracted DNA repeat in LHX3 intron

5 is associated with aberrant splicing and pituitary dwarfism in German shepherd dogs. PLoS

One 2011; 6:e27940.

Voorbij AM, Leegwater PA, Kooistra HS. Pituitary dwarfism in Saarloos and Czechoslovakian

wolfdogs is associated with a mutation in LHX3. J Vet Intern Med. 2014; Nov-Dec;28(6):1770-4.

Thaiwong T, Corner S, La Forge S, Kiupel M. Dwarfism in Tibetan Terrier dogs with an LHX3

mutation. J Vet Diagn Invest 2021; 1-4.