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Gnathodiaphyseal dysplasia (GDD) is a bone dysplasia characterized by bone fragility, frequent bone fractures at a young age, cemento-osseous lesions of the jaw bones, bowing of tubular bones (tibia and fibula) and diaphyseal sclerosis of long bones associated with generalized osteopenia. GD follows an autosomal dominant mode of transmission.
Data assembled from 8 of 12 sources · Last updated Oct 3, 2026, 8:12 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center
Features include very common findings: Thickened cortex of long bones and Broad jaw; and common findings: Mandibular osteomyelitis. 10 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Bones and joints | 8 | Mild bone density loss (osteopenia), Bowing of the long bones, Increased susceptibility to fractures |
Head and neck | 1 | Mandibular osteomyelitis |
The spectrum of ANO5-related muscle disease is a continuum ranging from exercise-induced myalgia and hyperCKemia to proximal and/or distal muscle weakness. The most common presentation is late-onset proximal lower limb weakness (limb-girdle muscular dystrophy R12 anoctamin-5-related [LGMD-R12]) . Less common is early adult-onset calf distal myopathy (Miyoshi muscular dystrophy 3 [MMD3]) . To date, more than 500 individuals have been identified with biallelic pathogenic variants in ANO5. The following description of the phenotypic features associated with this condition is based on these reports. Onset of the proximal weakness in LGMD-R12 is in the fourth or fifth decade (range: age 15-70 years); onset of calf weakness in MMD3 is around age 30 years.
Source: GeneReviews — "ANO5-Related Muscle Disease"
ANO5 encodes anoctamin 5 (913 aa). Plays a role in plasma membrane repair in a process involving annexins. Does not exhibit calcium-activated chloride channel (CaCC) activity Highest expression in Muscle Skeletal (26.6 TPM) and Heart Atrial Appendage (11.4 TPM).
Gnathodiaphyseal dysplasia is caused by mutations in the ANO5 gene on chromosome 11.
The ANO5 protein participates in ANO5:ANO5:Ca2+, ANO6:ANO6:Ca2+ and ANO5, ANO6 expose PS, PE on endothelial cells pathways.
ANO5 is classified as a druggable target (Transporter category) with score 0.0.
Only limited genotype-phenotype correlations have been identified. Individuals with biallelic loss-of-function variants have been reported to use walking aids at a significantly earlier age than individuals with pathogenic variants that are expected to lead to partial or reduced function. Individuals homozygous for ANO5 pathogenic variant showed a significantly later use of walking aids compared to individuals with other ANO5 pathogenic variants .
Source: GeneReviews — "ANO5-Related Muscle Disease"
No consensus clinical diagnostic criteria for ANO5-related muscle disease have been published.
ANO5-related muscle disease should be suspected in probands with the following clinical, laboratory, electrophysiology, imaging, and histopathology findings and family history.
Clinical findings
Asymmetric muscle weakness and atrophy, especially in the thigh muscles, with late adult onset (mean onset: age 35 years)
Calf distal myopathy of early adult onset (mean onset: age 30 years)
Exercise-induced myalgia
Source: GeneReviews — "ANO5-Related Muscle Disease"
Limb-girdle muscular dystrophy (LGMD). The differential diagnosis of limb-girdle muscular dystrophy R12 anoctamin-5-related (LGMD-R12) includes all the LGMDs (see OMIM phenotypic series LGMD, autosomal recessive and LGMD, autosomal dominant). Of particular note is LGMD-R2 dysferlin-related (formerly LGMD2B) with primarily proximal weakness. LGMD-R2 is a dysferlinopathy characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles in adolescence or young adulthood, with slow progression. Distal myopathy. Muscle MRI, muscle pathology, and mode of inheritance may be useful in distinguishing between distal myopathies in the differential diagnosis of Miyoshi muscular dystrophy 3 (MMD3) . Table 2. Genes Associated with Calf-Predominant Distal Myopathies in the Differential Diagnosis of Miyoshi Muscular Dystrophy 3
Gene | Disorder | MOI | Age of Onset | Initial Muscle Group Involved |
|---|
Genetic testing for ANO5 is available. Testing is considered confirmatory for diagnosis.
No approved treatments are currently available for gnathodiaphyseal dysplasia. The disease remains an area of unmet medical need.
No clinical practice guidelines for ANO5-related muscle disease have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.
To establish the extent of disease and needs of an individual diagnosed with ANO5-related muscle disease, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.
Table 3.
ANO5-Related Muscle Disease: Recommended Evaluations Following Initial Diagnosis
System/Concern | Evaluation | Comment
| Neurologic eval manual muscle force measurement | To establish a baseline for future assessment of disease progression possible need for assistive devices
Muscle imaging (CT or MRI) | To identify pattern of affected muscles in detail
| Cardiac eval incl echocardiogram EKG |
| By genetics professionals1 | To obtain a pedigree inform affected persons their families re nature, MOI, implications of ANO5-related muscle disease to facilitate medical personal decision making
MOI = mode of inheritance
1. Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)
No definitive treatments for the limb-girdle muscular dystrophies exist. Management is tailored to each individual and each specific subtype.
Table 4.
Source: GeneReviews — "ANO5-Related Muscle Disease"
Heavy muscle force training of weak muscles should be avoided, as very high plasma CK concentration has been measured after strenuous exercise . The use of statins, which can induce muscle pain and worsen muscle weakness, should be avoided. If absolutely necessary for the health of the individual, statin use requires extra monitoring of clinical status, especially at the beginning of treatment.
Source: GeneReviews — "ANO5-Related Muscle Disease"
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
Source: GeneReviews — "ANO5-Related Muscle Disease"
View trials for gnathodiaphyseal dysplasia
To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.
Table 5.
ANO5-Related Muscle Disease: Recommended Surveillance
System/Concern | Evaluation | Frequency
| Eval of muscle strength functional status | Every 6-12 mos
| EKG | Every 3 yrs
Source: GeneReviews — "ANO5-Related Muscle Disease"
Phenotype severity distribution: 2 very common features, 1 common feature.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for gnathodiaphyseal dysplasia.
8 publications have been identified in PubMed for gnathodiaphyseal dysplasia. Research spans Basic Science / Preclinical (63%), Review / Meta-Analysis (25%), and Case Report / Case Series (13%).
Li H (2026). [PMID: 41717545](https://pubmed.ncbi.nlm.nih.gov/41717545/). *Frontiers in endocrinology*. [Basic Science / Preclinical]
Koguchi R (2025). [PMID: 40861765](https://pubmed.ncbi.nlm.nih.gov/40861765/). *Cureus*. [Case Report / Case Series]
Li H (2025). [PMID: 39866532](https://pubmed.ncbi.nlm.nih.gov/39866532/). *Bone reports*. [Basic Science / Preclinical]
Liu X (2025). [PMID: 40049314](https://pubmed.ncbi.nlm.nih.gov/40049314/). *Experimental cell research*. [Basic Science / Preclinical]
Fanning M (2025). [PMID: 41193275](https://pubmed.ncbi.nlm.nih.gov/41193275/). *Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery*. [Review / Meta-Analysis]
Wang S (2025). [PMID: 40508076](https://pubmed.ncbi.nlm.nih.gov/40508076/). *International journal of molecular sciences*. [Basic Science / Preclinical]
Zhang S (2025). [PMID: 40067389](https://pubmed.ncbi.nlm.nih.gov/40067389/). *JCI insight*. [Basic Science / Preclinical]
Cuvelier V (2024). [PMID: 38922934](https://pubmed.ncbi.nlm.nih.gov/38922934/). *Prenatal diagnosis*. [Review / Meta-Analysis]
Serum CK Concentration
Muscle Biopsy |
|---|
ADSS1 | Distal myopathy 5 (OMIM 617030) | AR | Adolescence | Posterior compartment in legs | Mildly | Myopathic changes, rimmed vacuoles, nemaline rods |
DYSF | Miyoshi myopathy 11 (See Dysferlinopathy.) | AR | 19 yrs (median age at onset) | Posterior compartment in legs | Often 10-100x normal | Myopathic changes |
FLNC | Myofibrillar myopathy 5 (OMIM 609524) | AD | Teenage yrs to fourth decade | Posterior compartment | Normal or slightly | — |
LDB3 | Myofibrillar myopathy 4 (Markesbery-Griggs distal myopathy) (OMIM 609452) | AD | 40 yrs | Posterior compartment in legs | Normal or slightly | Vacuolar myofibrillar myopathy |
MYOT | Myofibrillar myopathy 3 (OMIM 609200) | AD | 40 yrs | Posterior anterior in legs | Slightly AD = autosomal dominant; AR = autosomal recessive; CK = creatine kinase; MOI = mode of inheritance Miyoshi myopathy 1 is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles. | — |
Source: GeneReviews — "ANO5-Related Muscle Disease"