Clinical characteristics.

PTH1R-related Jansen metaphyseal chondrodysplasia (PTH1R-JMC) is characterized by short-limb short stature with swelling of the joints in the extremities, bowing of the lower extremities, mild-to-severe scoliosis, hypercalcemia with low-normal or suppressed parathyroid hormone, and kidney stones. Craniofacial features can include scaphocephaly, prominent forehead and supraorbital ridge, downslanted palpebral fissures, hypertelorism, telecanthus, wide nasal bridge, low-set ears, and retrognathia. Dental manifestations include delayed eruption with impaction, crowding, and malocclusion. Radiographs show bowing of the long bones, flaring or widening of the metaphyses, short phalanges, sclerosis of the skull base, fragmented vertebra, and, in some individuals, scoliosis. Although motor skills may be delayed, intelligence is normal.

Diagnosis/testing.

The diagnosis of PTH1R-JMC is established in a proband with characteristic clinical and radiographic findings and a heterozygous pathogenic variant in PTH1R identified by molecular genetic testing.

Management.

Treatment of manifestations: Physical therapy, shoe lifts for limb length discrepancy, assisted devices for mobility, or surgical intervention as indicated; encourage healthy diet and physical activity as tolerated; treatment of severe limb deformity and scoliosis per orthopedist; cranial vault expansion when necessary; orthodontic treatment when necessary; treatment of hearing deficits per otolaryngologist and/or audiologist; treatment of eye and visual deficits per ophthalmologist; intake of plenty of fluids to reduce risk of hypercalcemia, hypercalciuria, nephrolithiasis, and nephrocalcinosis; consider bisphosphonates if necessary for severe hypercalcemia; treatment of airway issues per pulmonologist; continuous positive airway pressure as needed for obstructive sleep apnea; encourage watchful sodium intake; drugs targeting the angiotensin receptor pathway as needed for elevated blood pressure.

Surveillance: Physical exam, limb length measurement, and growth assessment every six to 12 months in children and adolescents; physical exam annually in adults; radiographs of extremities, spine radiographs, and skull CT as needed; examination for dental and orthodontic issues with radiographs every six to 12 months; audiogram and tympanogram every one to two years; visual field exam and optical coherence tomography every one to two years; annual laboratory assessment of serum calcium, serum phosphorus, and 24-hour urine calcium; annual kidney and urinary tract ultrasound; assess for signs and symptoms of dyspnea at each visit; pulmonary function testing as indicated; blood pressure measurement at each visit; consider echocardiogram in those with dyspnea or severe scoliosis as clinically indicated.

Agents/circumstances to avoid: Contact sports and other high-risk activities in those with significant skeletal involvement.

Genetic counseling.

PTH1R-JMC is inherited in an autosomal dominant manner. Although some individuals diagnosed with PTH1R-JMC have the disorder as the result of a pathogenic variant inherited from a heterozygous parent manifesting the skeletal features of the disorder, most individuals have the disorder as the result of a de novo pathogenic variant. Each child of an individual with PTH1R-JMC has a 50% chance of inheriting the PTH1R pathogenic variant. Once the PTH1R pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Suggestive Findings

PTH1R-JMC should be suspected in probands with the following clinical, laboratory, and imaging findings and family history.

Clinical findings

• Growth deceleration of postnatal onset or severe short-limb short stature
• Skeletal deformities: short limbs, swelling of the joints of the extremities, bowing of the lower extremities (see Figure 1), and mild-to-severe scoliosis
• History of kidney stones
• Craniofacial features: scaphocephaly, prominent forehead and supraorbital ridge, downslanted palpebral fissures, hypertelorism, telecanthus, wide nasal bridge, low-set ears, and retrognathia (See Figure 2.)
• Dental findings: delayed eruption with impaction, crowding, and malocclusion (See Figure 3.)
• Hypertension or elevated blood pressure
• Normal intellect

Figure 1.

Skeletal deformities in individuals with PTH1R-related Jansen metaphyseal chondrodysplasia. Note deformities in the upper (A) and lower (B) extremities in a female age 45 years and severe scoliosis with asymmetric shoulders seen in another affected individual (more...)

Figure 2.

Craniofacial phenotype in individuals with PTH1R-related Jansen metaphyseal chondrodysplasia A, B. Male age 12 years

Figure 3.

Dental manifestations in individuals with PTH1R-related Jansen metaphyseal chondrodysplasia. Reconstructed panoramic views from skull CT from: A. Male age 16 years with multiple submerged primary molars and impacted permanent canines, premolars, and molars; (more...)

Laboratory findings

• Hypercalcemia (or high-normal serum calcium levels) with low or suppressed serum PTH
• Increased bone turnover markers such as bone-specific alkaline phosphatase (ALK), osteocalcin, and serum N-terminal telopeptide (NTx)
• Serum phosphorus may be low or low-normal
• Hypercalciuria

Imaging findings

• Rickets-like metaphyseal changes may be evident prenatally or in infancy [Savoldi et al 2013].
• Radiographs of the extremities show bowing of long bones, flaring or widening of the metaphyses, and short phalanges (see Figure 4).
• Radiographs of the axial skeleton reveal sclerosis of the skull base, fragmented vertebra, and, in some individuals, scoliosis [Obiezu et al 2024a].
• Head CT shows bilateral expansile bony lesions of the skull base (i.e., sphenoid, temporal) and facial bones. There may be obliteration of the sinuses (e.g., sphenoid, maxillary, mastoid air cells) and irregular, abnormal-appearing atlantooccipital and temporomandibular joints [Obiezu et al 2024a, Obiezu et al 2024b].
• Kidney ultrasound may show mild-to-moderate nephrocalcinosis with increased echogenicity of the renal pyramids.

Figure 4.

CT and radiographs of skeletal manifestations of PTH1R-related Jansen metaphyseal chondrodysplasia A. Axial CT of the cranial base in a male age 17 years with diffuse expansile lesions in anterior skull base with extensive involvement of the sphenoid (more...)

Family history may be consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). However, PTH1R pathogenic variants are de novo in most individuals, and absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of PTH1R-JMC is established in a proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in PTH1R identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of a heterozygous PTH1R variant of uncertain significance does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Clinical Description

PTH1R-related Jansen metaphyseal chondrodysplasia (PTH1R-JMC) is an ultra-rare disorder characterized by short-limb short stature with swelling of the joints in the extremities and hypercalcemia with low-normal or suppressed parathyroid hormone (PTH) [Saito et al 2018]. To date, at least 30 individuals have been identified with a pathogenic variant in PTH1R [Saito et al 2018]. There is a wide spectrum of clinical variability. However, the natural history of PTH1R-JMC and the full spectrum of its manifestations has not been adequately described.

Skeletal features may not be clinically evident at birth. Postnatal growth failure and accompanying skeletal deformities typically become apparent within early childhood [Olney & Bober 2018]. Skeletal deformities may contribute to delayed motor milestones such as pulling to stand or walking [Nampoothiri et al 2016]. Individuals have short limbs with bowed legs and waddling gait. Other features include clinodactyly, short, clubbed fingers, and scoliosis.

Craniofacial features. Individuals with PTH1R-JMC have a distinct craniofacial appearance with a range in severity. Craniofacial features include scaphocephaly, prominent forehead and supraorbital ridge, downslanted palpebral fissures, hypertelorism, wide nasal bridge, maxillary hyper- or hypoplasia, low-set ears, and retrognathia (see Figure 2) [Obiezu et al 2024b].

In addition to the distinctive craniofacial appearance (see Figure 3), other findings can include craniosynostosis affecting any of the cranial sutures and necessitating surgical correction has been described.

The craniofacial anomalies may result in functional deficits such as hearing loss [Obiezu et al 2024a], vision loss, and/or facial palsy.

Dental characteristics include flat palate, malocclusion including delayed dental eruption, impaction, and overcrowding [Obiezu et al 2024a]. Individuals with PTH1R-JMC report a history of multiple teeth extractions to address overretained teeth. Enamel hypoplasia has also been described and may be a feature of PTH1R-JMC.

Hearing loss may result due to abnormalities of the ossicles and tympanic membrane rigidity leading to conductive hearing deficits or narrowing of the internal auditory canal leading to sensorineural hearing deficits. Mixed hearing loss may be present. The typical age of onset and the overall course of hearing loss varies based on disease severity. Hearing loss may be progressive based on the underlying pathomechanism.

Ophthalmologic manifestations. Narrowing of the optic canal can lead to compression of the optic nerve and progressive optic neuropathy. Findings such as optic nerve pallor and decreased retinal nerve fiber layer on optical coherence tomography may be seen in individuals with clinical or subclinical visual deficits [Obiezu et al 2024b]. Similar to hearing loss, the typical age of onset of ophthalmologic manifestations and their overall course varies based on disease severity. Visual field deficits may be progressive based on the underlying pathomechanism.

Mineral homeostasis and kidney manifestations. Individuals with PTH1R-JMC are known to have high or high-normal serum calcium concentration with appropriately normal or low PTH concentration. Serum phosphate concentration appears to be largely within normal range. Hypercalciuria, seen in some individuals, can result in nephrolithiasis, nephrocalcinosis, and consequent chronic kidney disease [Saito et al 2018]. Not all individuals develop hypercalcemia; however, when present, it appears to improve with age. End-stage kidney disease requiring kidney replacement therapy has been described.

Upper airway compromise may be due to stenosis of the airway and anterior hyoid bone displacement and can increase the risk for obstructive sleep apnea (see Management).

Hypertension and/or elevated blood pressure has been described as early as infancy [Gabbett et al 2020]. While the underlying cause of hypertension is unknown, it may be due to the underlying disease pathomechanism.

Prognosis. There are no data regarding longevity in individuals with PTH1R-JMC.

Genotype-Phenotype Correlations

Given the ultra-rare nature of PTH1R-JMC, studies detailing genotype-phenotype correlation have not been performed.

Penetrance

PTH1R-JMC has a high penetrance, and individuals with a PTH1R-JMC-related pathogenic variant are likely to develop some clinical and/or radiographic manifestations. There is wide heterogeneity in the phenotype in terms of clinical manifestations, onset, and severity. Short-limbed dwarfism appears to be a highly penetrant manifestation, seen in almost all affected individuals [Saito et al 2018].

Nomenclature

In the 2023 revision of the Nosology of Genetic Skeletal Disorders, PTH1R-JMC is referred to as metaphyseal dysplasia, Jansen type, PTHR1-related and is included in the skeletal disorders of the parathyroid hormone signaling cascade group [Unger et al 2023].

Prevalence

PTH1R-JMC is an ultra-rare disorder; at least 30 individuals are known to have a genetically confirmed diagnosis (see The Jansen's Foundation).

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PTH1R-JMC, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Treatment of Manifestations

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 5). There is no approved treatment for PTH1R-JMC, although a trial evaluating the safety and efficacy of PTH-inverse agonist (PTH-IA) is expected to start enrolling soon (see Therapies Under Investigation).

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 6 are recommended. There is no evidence informing the frequency of surveillance in individuals with PTH1R-JMC. The recommendations are based on the authors' experience.

Agents/Circumstances to Avoid

Contact sports and other high-risk activities should likely be avoided in those with significant skeletal involvement. Individuals with PTH1R-JMC should be encouraged to participate in low-impact exercise as tolerated, such as swimming.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Although women with PTH1R-JMC may conceive and safely deliver live births, they may face physical restraints due to the potential for increased perinatal morbidity and mortality requiring special precautions [Savarirayan et al 2018]. The risk of preterm delivery in women with skeletal dysplasias and short stature is elevated in comparison to the general population [O'Connor et al 2022]. Furthermore, PTH1R-JMC can affect the rib cage and spine, potentially leading to respiratory problems during pregnancy and delivery. Women with PTH1R-JMC are not known to experience worsening of the disease during pregnancy.

See MotherToBaby for further information on medication use during pregnancy.

Therapies Under Investigation

PTH-IA is a 30-amino-acid peptide expected to act as an inverse agonist, decreasing the proportion of parathyroid hormone/parathyroid hormone-related peptide receptors (PTH1R) in the constitutively active state, leading to a reduction in basal cAMP signaling. To date, information on PTH-IA is limited to cell and animal models [Saito et al 2018, Noda et al 2020]. An Investigational New Drug approval was granted to a Phase I/II study evaluating the safety and efficacy of PTH-IA, which is expected to start enrolling soon.

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.

Mode of Inheritance

PTH1R-related Jansen metaphyseal chondrodysplasia (PTH1R-JMC) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

• Some individuals diagnosed with PTH1R-JMC have the disorder as the result of a pathogenic variant inherited from a heterozygous parent manifesting the skeletal features of the disorder [Nampoothiri et al 2016].
• Most individuals diagnosed with PTH1R-JMC have the disorder as the result of a de novo PTH1R pathogenic variant.
• If the proband appears to be the only affected family member (i.e., a simplex case), molecular genetic testing of the parents of the proband can establish their genetic status and inform recurrence risk assessment. Note: Parental molecular genetic testing is typically not required in the absence of any clinical features but can help to confirm the de novo occurrence of a PTH1R pathogenic variant.
• If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
  • The proband has a de novo pathogenic variant.
  • The proband inherited a pathogenic variant from a parent with gonadal (or somatic and gonadal) mosaicism (gonadal mosaicism has not been reported in PTH1R-JMC to date).* Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ (gonadal) cells only.
    * A parent with somatic and gonadal mosaicism for a PTH1R pathogenic variant may be mildly/minimally affected.

Sibs of a proband. The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:

• If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. PTH1R-JMC is associated with high penetrance; individuals with a heterozygous PTH1R are likely to have manifestations of the disorder.
• If the proband has a known PTH1R pathogenic variant that cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the possibility of parental gonadal mosaicism [Rahbari et al 2016].
• If the parents have not been tested for the PTH1R pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for PTH1R-JMC because of the possibility of parental gonadal mosaicism.

Offspring of a proband. Each child of an individual with PTH1R-JMC has a 50% chance of inheriting the PTH1R pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the PTH1R pathogenic variant, the parent's family members may be at risk.

Related Genetic Counseling Issues

Family planning

• The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected.

Prenatal Testing and Preimplantation Genetic Testing

Once the PTH1R pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Molecular Pathogenesis

PTH1R encodes the parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R), which is abundantly expressed in kidney, osteoblasts, and growth plate chondrocytes. Normal activation of PTH1R due to binding of parathyroid hormone (PTH) in the proximal convoluted tubules of the kidney results in increased urinary phosphate excretion and increased formation of 1,25-dihydroxyvitamin D, which increases intestinal absorption of calcium and phosphate. Activation of PTH1R:

• In the distal convoluted tubules of the kidney results in calcium reabsorption;
• In osteoblasts results in upregulation of RANKL, which stimulates osteoclast precursor cells to differentiate to mature osteoclasts;
• In the pre-hypertrophic growth plate chondrocytes slows their differentiation into hypertrophic chondrocytes, thus regulating bone lengthening and linear growth.

Mechanism of disease causation. Gain of function due to constitutive activation of PTH1R. Five PTH1R gain-of-function pathogenic variants that affect three residues of PTH1R have been identified in individuals with PTH1R-related Jansen metaphyseal chondrodysplasia (PTH1R-JMC) (see Table 7). PTH1R-JMC results from constitutive activation of PTH1R. Pathogenic variants lock the receptor in an active state, resulting in its ligand-independent activation.

Author Notes

Fiona Obiezu, MD, is an incoming Plastic Surgery Resident at University of Las Vegas who completed the Medical Research Scholars Program at National Institutes of Health. She is an aspiring craniofacial surgeon with an interest in rare skeletal disorders.

Alison Boyce, MD, is a pediatric endocrinologist at the National Institutes of Health with an interest in rare and pediatric skeletal disorders. Web page: www.nidcr.nih.gov

Harald Jüppner, MD, is a nephrologist at Massachusetts General Hospital with an interest in genetic disorders affecting calcium and phosphate homeostasis as well as bone disorders. Web page: researchers.mgh.harvard.edu

Smita Jha, MD, is an endocrinologist at the National Institutes of Health with a special interest in disorders of parathyroid hormone signaling or function such as PTH1R-related Jansen metaphyseal chondrodysplasia (PTH1R-JMC). Web page: www.niddk.nih.gov

Drs Smita Jha (vog.hin@ahj.atims) and Alison Boyce (vog.hin@ecyob.nosila) are actively involved in clinical research regarding individuals with PTH1R-JMC. They would be happy to communicate with persons who have any questions regarding diagnosis of PTH1R-JMC or other considerations.

Acknowledgments

This research was supported by the Intramural and Extramural Research Program of the NIH/NIDDK. We wish to express our gratitude to the patients and their families for participation in the research and to the trainees and staff at the NIH Clinical Research Center for providing clinical care to the study participants.

Revision History

• 10 July 2025 (sw) Review posted live
• 2 April 2025 (sj) Original submission

Literature Cited

• Gabbett MT, Jeavons CJ, Gray PH. Severe hypertension-an infantile feature of Jansen metaphyseal chondrodysplasia? Am J Med Genet Part A. 2020;182:768-72. [PubMed: 31977144]
• Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM, Malinowski J, Massingham LJ, Miller D, Yu TW, Hisama FM, Directors ABo. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23:2029-37. [PubMed: 34211152]
• Nampoothiri S, Fernandez-Rebollo E, Yesodharan D, Gardella TJ, Rush ET, Langman CB, Juppner H. Jansen metaphyseal chondrodysplasia due to heterozygous H223R-PTH1R mutations with or without overt hypercalcemia. J Clin Endocrinol Metab. 2016;101:4283-9. [PMC free article: PMC5095231] [PubMed: 27410178]
• Noda H, Guo J, Khatri A, Dean T, Reyes M, Armanini M, Brooks DJ, Martins JS, Schipani E, Bouxsein ML, Demay MB, Potts JT, Jr., Jüppner H, Gardella TJ. An inverse agonist ligand of the PTH receptor partially rescues skeletal defects in a mouse model of Jansen's metaphyseal chondrodysplasia. J Bone Miner Res. 2020;35:540-9. [PMC free article: PMC8050614] [PubMed: 31693237]
• Obiezu F, Almpani K, Kim HJ, Zalewski C, Chu E, Jahanmir G, Roszko KL, Boyce A, Farhadi F, Weinstein LS, Gafni RI, Ferreira CR, Juppner H, Collins MT, Lee JS, Jha S. Jansen metaphyseal chondrodysplasia: analysis of craniofacial manifestations. JBMR Plus. 2024a;9:ziae156. [PMC free article: PMC11736719] [PubMed: 39830149]
• Obiezu F, Magone De Quadros Costa MT, Huryn LA, Pan K, Almpani K, Ninan A, Roszko KL, Weinstein LS, Gafni RI, Ferreira CR, Lee J, Collins MT, Jha S. Ocular findings in Jansen metaphyseal chondrodysplasia. JBMR Plus. 2024b;8:ziae089. [PMC free article: PMC11299511] [PubMed: 39108358]
• O'Connor D, Menzies R, Cao X, Berndl A. Preterm birth risk in women with skeletal dysplasias and short stature. J Pediatr Rehabil Med. 2022;15:639-46. [PubMed: 36530102]
• Olney RC, Bober MB. Skeletal Dysplasias. In: Radovick S, Misra M, eds. Pediatric Endocrinology. Springer, Cham; 2018:175-96.
• Rahbari R, Wuster A, Lindsay SJ, Hardwick RJ, Alexandrov LB, Turki SA, Dominiczak A, Morris A, Porteous D, Smith B, Stratton MR, Consortium UK, Hurles ME. Timing, rates and spectra of human germline mutation. Nat Genet. 2016;48:126-33. [PMC free article: PMC4731925] [PubMed: 26656846]
• Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Committee ALQA. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-24. [PMC free article: PMC4544753] [PubMed: 25741868]
• Saito H, Noda H, Gatault P, Bockenhauer D, Loke KY, Hiort O, Silve C, Sharwood E, Martin RM, Dillon MJ, Gillis D, Harris M, Rao SD, Pauli RM, Gardella TJ, Juppner H. Progression of mineral ion abnormalities in patients with Jansen metaphyseal chondrodysplasia. J Clin Endocrinol Metab. 2018;103:2660-9. [PMC free article: PMC6486824] [PubMed: 29788189]
• Savarirayan R, Rossiter JP, Hoover-Fong JE, Irving M, Bompadre V, Goldberg MJ, Bober MB, Cho TJ, Kamps SE, Mackenzie WG, Raggio C, Spencer SS, White KK, Skeletal Dysplasia Management C. Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia. Am J Obstet Gynecol. 2018;219:545-62. [PubMed: 30048634]
• Savoldi G, Izzi C, Signorelli M, Bondioni MP, Romani C, Lanzi G, Moratto D, Verdoni L, Pinotti M, Prefumo F, Superti-Furga A, Pilotta A. Prenatal presentation and postnatal evolution of a patient with Jansen metaphyseal dysplasia with a novel missense mutation in PTH1R. Am J Med Genet Part A. 2013;161A:2614-9. [PubMed: 23950054]
• Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD((R))): optimizing its use in a clinical diagnostic or research setting. Hum Genet. 2020;139:1197-207. [PMC free article: PMC7497289] [PubMed: 32596782]
• Unger S, Ferreira CR, Mortier GR, Ali H, Bertola DR, Calder A, Cohn DH, Cormier-Daire V, Girisha KM, Hall C, Krakow D, Makitie O, Mundlos S, Nishimura G, Robertson SP, Savarirayan R, Sillence D, Simon M, Sutton VR, Warman ML, Superti-Furga A. Nosology of genetic skeletal disorders: 2023 revision. Am J Med Genet Part A. 2023;191:1164-209. [PMC free article: PMC10081954] [PubMed: 36779427]