Clinical characteristics.

INPPL1-related opsismodysplasia is characterized by prenatal-onset short stature, short, bowed limbs, characteristic facial features (relative macrocephaly, prominent forehead, midface retrusion, depressed nasal bridge, short nose, anteverted nares, relatively long philtrum), narrow thorax, small hands and feet, delayed epiphyseal mineralization, metaphyseal cupping, and platyspondyly. Complications include increased risk of fractures, cervical spine abnormalities, scoliosis, bone pain, respiratory issues, and delayed gross motor skills. Some individuals have cardiac or kidney manifestations. Prognosis is variable with perinatal demise in some infants.

Diagnosis/testing.

The diagnosis of INPPL1-related opsismodysplasia is established in a proband with characteristic clinical and radiographic features and biallelic pathogenic variants in INPPL1 identified by molecular genetic testing.

Management.

Targeted therapy: Intravenous bisphosphonate therapy has improved bone mineral density and gross motor function in two individuals with INPPL1-related opsismodysplasia.

Supportive care: Cervical spine complications should be managed by specialists familiar with skeletal dysplasias involving the spine including an orthopedist and neurosurgeon; surgical stabilization should be performed to prevent progressive myelopathy; management of scoliosis per orthopedist with surgery when indicated; management of hypophosphatemia, renal phosphate wasting, and bone demineralization per endocrinologist; treatment of respiratory insufficiency per pulmonologist; vaccines to prevent respiratory illnesses; CPAP and surgical management as needed for sleep apnea; feeding therapy with modification of fluid or food texture as needed for swallowing difficulties; aerodigestive evaluation for endoscopy and surgery as needed; management of cardiac manifestations per cardiologist; management of renal manifestations per nephrologist and/or urologist; amplification/hearing device and/or surgery when indicated for hearing impairment; social work and family support.

Surveillance: Flexion/extension cervical spine MRI every three months until cervical instability can be excluded in those with instability, risk of cervical cord compression, or limited radiograph interpretation; then MRI every two to three years, preoperatively, and when indicated. Clinical examination for scoliosis every six to 12 months with radiographs when indicated; endocrinology evaluation for hypophosphatemia and renal phosphate wasting every six to 12 months and when indicated; DXA scan when indicated; pulmonary function studies, chest radiographs, swallowing evaluation, and sleep study every six to 12 months and when indicated per pulmonologist; swallowing evaluation as indicated to evaluate for aspiration; developmental assessment to assess gross motor skills annually or as needed; rehabilitation medicine, physical therapy, and occupational therapy consultations when indicated to evaluate function and need for adaptive devices and to support activities of daily living and mobility; clinical cardiac examination with frequency per cardiologist; audiology evaluation annually or as needed; ENT and orthodontic evaluations as needed; assess family and social work needs at each visit.

Agents/circumstances to avoid: Individuals with cervical spine instability or who are at risk for cervical spine instability should avoid extreme neck flexion and extension, contact sports, and other at-risk activities. Individuals with bone demineralization should avoid contact sports and other activities associated with an increased risk for fractures.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic at-risk sibs of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of targeted therapy.

Genetic counseling.

INPPL1-related opsismodysplasia is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an INPPL1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the INPPL1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.

Suggestive Findings

INPPL1-related opsismodysplasia should be suspected in a proband with the following clinical, laboratory, and imaging findings and family history.

Clinical findings

• Prenatal-onset disproportionate short stature with short limbs
• Characteristic facial features (relative macrocephaly, prominent forehead, midface retrusion, depressed nasal bridge, short nose, anteverted nares, and a relatively long philtrum)
• Narrow thorax
• Small hands and feet
• Respiratory insufficiency

Laboratory findings

• Severe renal phosphate wasting
• Hypophosphatemia

Imaging findings

• Shortened, bowed long bones
• Narrow thorax
• Delayed epiphyseal mineralization (See Figure 1 and Figure 2.)
• Platyspondyly
• Metaphyseal cupping (See Figure 3.)
• Short and broad metacarpals and phalanges with square appearance, flared metaphyses, and irregular ossification (patchy, with some areas less ossified than others)
• Additional radiographic findings can include handlebar clavicles, hypoplastic and square iliac wings, hypoplastic pubic bones, horizontal acetabular roof, acetabular dysplasia, coxa vara, broad femoral heads, small tapered middle phalanges, and calcaneal spurs.

Figure 1.

AP and lateral spine radiographs and AP chest radiograph show undermineralization of the vertebrae, platyspondyly, and narrow thorax.

Figure 2.

AP lower extremity radiographs from the first week of life show decreased mineralization, delayed ossification of the epiphyses, and metaphyseal flaring of the long bones.

Figure 3.

AP hand and feet radiographs at birth. The metacarpals, metatarsals, and phalanges have flared metaphyses with metaphyseal cupping. There is delayed carpal ossification.

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of INPPL1-related opsismodysplasia is established in a proband with suggestive findings and biallelic pathogenic (or likely pathogenic) variants in INPPL1 identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" 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 biallelic INPPL1 variants of uncertain significance (or of one known INPPL1 pathogenic variant and one INPPL1 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

INPPL1-related opsismodysplasia is characterized by prenatal-onset short stature, short limbs, small hands and feet, narrow thorax, dysmorphic facial features (including relative macrocephaly, prominent forehead, midface retrusion, depressed nasal bridge, short nose, anteverted nares, and relatively long philtrum), delayed epiphyseal mineralization, metaphyseal cupping, and platyspondyly. To date, 35 individuals have been identified with biallelic pathogenic variants in INPPL1 [Below et al 2013, Huber et al 2013, Iida et al 2013, Li et al 2014, Feist et al 2016, Ghosh et al 2017, Abumansour et al 2021, Silveira et al 2021]. The following description of the phenotypic features associated with this condition is based on these reports.

Prenatal. Reported prenatal ultrasound findings reflect the underlying skeletal differences, including short limbs, short long bones, short hands and feet, narrow thorax, bell-shaped thorax, platyspondyly, and decreased bone echogenicity. Increased nuchal translucency, cystic hygroma, and hydrops have been reported. Both oligohydramnios and polyhydramnios have been reported.

Craniofacial features. The described craniofacial configuration frequently includes relative macrocephaly, large fontanelles, prominent forehead, tall forehead, frontal bossing, hypertelorism, midface retrusion, depressed nasal bridge, short nose, anteverted nares, and relatively long philtrum. Macrocephaly (head circumference greater than two standard deviations [SD] above the mean) has been reported in a small number of individuals [Below et al 2013, Ghosh et al 2017]. Other reported craniofacial features include coarse facies, brachycephaly, proptosis, shallow orbits, low-set ears, high-arched palate, macro- or microstomia, retrognathia, micrognathia, and short neck.

Growth. Prenatal and postnatal growth deficiency are reported in all affected individuals. Short stature is disproportionate, with short limbs. Below et al [2013] reported birth lengths ranging from 43 to 49 cm, but the corresponding gestational ages at birth were not clearly indicated. Growth deficiency is progressive. One affected female had a birth length of 38 cm (at full term) and height of 65 cm (more than 6 SD below the mean) at age nine years [Iida et al [2013]. Li et al [2014] reported progressive short stature in the first two years of life in a preterm female; height at age seven years was 78 cm, and final adult height was 101 cm at age 21 years.

Musculoskeletal manifestations

• Osteopenia leads to bowing of the long bones and an increased risk of fractures. To date, fractures have not been reported at birth. Below et al [2013] reported fractures in three individuals, including rib fractures in one child at age three years. Fractures of the radius and fibulae were reported in one individual at age seven years [Li et al 2014]. Increased risk for fractures is likely related to the extent of bony demineralization.
• Cervical spine complications include odontoid hypoplasia, os odontoideum, small foramen magnum, and cervical spinal canal stenosis.
• Scoliosis. Huber et al [2013] described severe scoliosis in three individuals; one individual underwent surgery for scoliosis. Age of onset and progression of scoliosis have not been specifically described in individuals with INPPL1-related opsismodysplasia, although scoliosis appears progressive [D Earl & K White, personal observations].
• Flexion contractures. Limited elbow extension has been noted at birth [Li et al 2014]. Mild elbow flexion contracture was reported in one individual and mild knee contracture in two individuals [Below et al 2013].
• Skeletal deformities and pain contribute to the challenges with walking. Such deformities may be surgically addressed. Walkers and wheelchairs are reported to aid mobility.

Respiratory issues. Contributions to respiratory insufficiency include restrictive lung disease from a narrow small thorax, severe scoliosis, pulmonary hypoplasia, pulmonary hypertension, recurrent infections (including pneumonia and aspiration pneumonia), reactive airway disease, obstructive sleep apnea, tracheomalacia, and bronchial narrowing. For some individuals, respiratory support includes intubation and mechanical ventilation. Two reported individuals required tracheostomy [Below et al 2013, Iida et al 2013]. Many individuals develop chronic lung disease. Respiratory issues may be severe and life-limiting.

Development. Affected individuals often have gross motor delays, with delayed onset of walking. One individual was described as wheelchair dependent [Below et al 2013]. Another individual started walking at age two years, stopped walking at age 2.5 years, but was then able to walk again after phosphate replacement therapy [Li et al 2014]. Two sibs demonstrated improved mobility following treatment with intravenous pamidronate [Khwaja et al 2015].

Normal intelligence has been reported, while cognitive impairment has not been specifically noted [Below et al 2013, Huber et al 2013, Iida et al 2013]. Cognitive outcomes are not uniformly commented upon across case reports. To date, the expectation is that cognition is not directly impacted in INPPL1-related opsismodysplasia.

Cardiac manifestations. Dilated cardiomyopathy was identified in one individual at age 2.5 years [Below et al 2013, Khwaja et al 2015]. Atrial septal defect was reported in two individuals [Below et al 2013, Abumansour et al 2021]. Tricuspid valve prolapse and mitral valve prolapse were reported in one individual at age 3.5 years [Huber et al 2013]. Abnormal tricuspid valve with regurgitation was identified at birth in one individual [Abumansour et al 2021].

Kidney manifestations. Absent kidney, hypoplastic kidney, and hydronephrosis have each been reported in one individual [Below et al 2013, Huber et al 2013, Abumansour et al 2021].

Other. Hearing loss and posterior cleft palate have each been reported in one individual [Below et al 2013].

Prognosis. At least two stillbirths have been reported in infants with INPPL1-related opsismodysplasia. Among the 21 liveborn infants, three were reported to have died in the perinatal period (30 minutes to 12 days) [Huber et al 2013, Abumansour et al 2021]. One infant died at 12 days after withdrawal of support for poor cardiorespiratory status in the context of apparently lethal skeletal dysplasia [Abumansour et al 2021]. There is variable life span; the oldest reported individual is age 24 years [Below et al 2013]. The cause of death beyond the perinatal period has not been specifically reported in individuals with INPPL1-related opsismodysplasia. In those with clinical and radiographic features of opsismodysplasia, diagnosed prior to the availability of molecular genetic testing, death secondary to respiratory failure has been reported [Cormier-Daire et al 2003].

Genotype-Phenotype Correlations

No clinically relevant genotype-phenotype correlations have been identified.

Nomenclature

INPPL1-related opsismodysplasia is included in Group 14 (severe spondylodysplastic dysplasias) of the Nosology of Genetic Skeletal Disorders: 2023 Revision [Unger et al 2023]. Of note, INPPL1-related opsismodysplasia overlaps Group 13 (spondyloepi[meta]physeal dysplasias) and Group 14 in the Skeletal Nosology.

Prevalence

INPPL1-related opsismodysplasia is rare and the exact prevalence is unknown.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with INPPL1-related opsismodysplasia, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Treatment of Manifestations

There is no cure for INPPL1-related opsismodysplasia.

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.

Agents/Circumstances to Avoid

Individuals with cervical spine instability or who are at risk for cervical spine instability should avoid extreme neck flexion and extension, contact sports, and other at-risk activities.

Individuals with bone demineralization should avoid contact sports and other activities associated with an increased risk for fractures.

Evaluation of Relatives at Risk

It is appropriate to clarify the genetic status of apparently asymptomatic at-risk sibs of an affected individual in order to identify as early as possible those who would benefit from prompt initiation of targeted therapy. Early diagnosis and initiation of treatment may improve outcome.

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

Pregnancy Management

To date, there are no published reports of pregnancies in women with INPPL1-related opsismodysplasia. For general recommendations regarding best practice guidelines for prenatal evaluation and delivery of individuals with skeletal dysplasia, see Savarirayan et al [2018].

Therapies Under Investigation

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.

Mode of Inheritance

INPPL1-related opsismodysplasia is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

• The parents of an affected child are presumed to be heterozygous for an INPPL1 pathogenic variant.
• Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for an INPPL1 pathogenic variant and to allow reliable recurrence risk assessment.
• If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, it is possible that one of the pathogenic variants identified in the proband occurred as a de novo event in the proband or as a postzygotic de novo event in a mosaic parent [Jónsson et al 2017]. If the proband appears to have homozygous pathogenic variants (i.e., the same two pathogenic variants), additional possibilities to consider include:
  • A single- or multiexon deletion in the proband that was not detected by sequence analysis and that resulted in the artifactual appearance of homozygosity;
  • Uniparental isodisomy for the parental chromosome with the pathogenic variant that resulted in homozygosity for the pathogenic variant in the proband.
• Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

• If both parents are known to be heterozygous for an INPPL1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
• Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Offspring of a proband. To date, individuals with INPPL1-related opsismodysplasia are not known to reproduce.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier of an INPPL1 pathogenic variant.

Carrier Detection

Carrier testing for at-risk relatives requires prior identification of the INPPL1 pathogenic variants in the family.

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, are carriers, or are at risk of being carriers.

Prenatal Testing and Preimplantation Genetic Testing

Once the INPPL1 pathogenic variants have 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

INPPL1 encodes phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 (also known as SH2 domain-containing inositol 5'-phosphatase 2, or SHIP2). SHIP2 not only dephosphorylates PI(3,4,5)P3 to generate PI(3,4)P2 but also acts as a docking protein that interacts with numerous components of the cytoskeleton. Loss of function of SHIP2 is the proposed mechanism of disease causation [Fradet & Fitzgerald 2017]. The exact role of SHIP2 in endochondral ossification is unknown.

Ghosh et al [2017] collected fibroblasts from affected individuals and apparently healthy, age-matched controls. The variants from the affected individuals were expected to lead to premature termination or abolish the catalytic activity of the SH2 domain. Fibroblasts derived from the affected individuals demonstrated lack of SHIP2 expression, deceased cell velocity, decreased cell migration, and increased cell adhesion. The authors suggested that the phosphatase activity and the roles of SHIP2 in adhesion, migration, proliferation, and polarity regulated chondrocyte organization and endochondral ossification. Therefore, loss of function may lead to the observed disorganization of the growth plate with absence of the columnar arrangement of proliferative cells as well as a reduced hypertrophic zone [Huber et al 2013].

Mechanism of disease causation. Loss of function

Revision History

• 12 June 2025 (sw) Review posted live
• 24 April 2024 (de) Original submission

Literature Cited

• Abumansour IS, Iskandarani RM, Edrees A, Javed F, Taher F, Hakeem GF. Prenatal-onset INPPL1-related skeletal dysplasia in two unrelated families: diagnosis and prediction of lethality. Clin Case Rep. 2021;9:e04079. [PMC free article: PMC8162397] [PubMed: 34094554]
• Below JE, Earl DL, Shively KM, McMillin MJ, Smith JD, Turner EH, Stephan MJ, Al-Gazali LI, Hertecant JL, Chitayat D, Unger S, Cohn DH, Krakow D, Swanson JM, Faustman EM, Shendure J, Nickerson DA, Bamshad MJ, University of Washington Center for Mendelian G. Whole-genome analysis reveals that mutations in inositol polyphosphate phosphatase-like 1 cause opsismodysplasia. Am J Hum Genet. 2013;92:137-43. [PMC free article: PMC3542462] [PubMed: 23273567]
• Cormier-Daire V, Delezoide AL, Philip N, Marcorelles P, Casas K, Hillion Y, Faivre L, Rimoin DL, Munnich A, Maroteaux P, Le Merrer M. Clinical, radiological, and chondro-osseous findings in opsismodysplasia: survey of a series of 12 unreported cases. J Med Genet. 2003;40:195-200. [PMC free article: PMC1735387] [PubMed: 12624139]
• Esen TE, Uzun ÖÜ, Ceylan AC. A mild skeletal dysplasia caused by a biallelic missense variant in the SLC35D1 gene. Mol Syndromol. 2023;14:498-503. [PMC free article: PMC10697730] [PubMed: 38058750]
• Feist C, Holden P, Fitzgerald J. Novel compound heterozygous mutations in inositol polyphosphate phosphatase-like 1 in a family with severe opsismodysplasia. Clin Dysmorphol. 2016;25:152-5. [PMC free article: PMC4995133] [PubMed: 27233067]
• Fradet A, Fitzgerald J. INPPL1 gene mutations in opsismodysplasia. J Hum Genet. 2017;62:135-40. [PMC free article: PMC5268411] [PubMed: 27708270]
• Furuichi T, Kayserili H, Hiraoka S, Nishimura G, Ohashi H, Alanay Y, Lerena JC, Aslanger AD, Koseki H, Cohn DH, Superti-Furga A, Unger S, Ikegawa S. Identification of loss-of-function mutations of SLC35D1 in patients with Schneckenbecken dysplasia, but not with other severe spondylodysplastic dysplasias group diseases. J Med Genet. 2009;46:562-8. [PMC free article: PMC4144354] [PubMed: 19508970]
• Ghosh S, Huber C, Siour Q, Sousa SB, Wright M, Cormier-Daire V, Erneux C. Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects. Hum Mutat. 2017;38:1731-9. [PubMed: 28869677]
• Huber C, Faqeih EA, Bartholdi D, Bole-Feysot C, Borochowitz Z, Cavalcanti DP, Frigo A, Nitschke P, Roume J, Santos HG, Shalev SA, Superti-Furga A, Delezoide AL, Le Merrer M, Munnich A, Cormier-Daire V. Exome sequencing identifies INPPL1 mutations as a cause of opsismodysplasia. Am J Hum Genet. 2013;92:144-9. [PMC free article: PMC3542463] [PubMed: 23273569]
• Iida A, Okamoto N, Miyake N, Nishimura G, Minami S, Sugimoto T, Nakashima M, Tsurusaki Y, Saitsu H, Shiina M, Ogata K, Watanabe S, Ohashi H, Matsumoto N, Ikegawa S. Exome sequencing identifies a novel INPPL1 mutation in opsismodysplasia. J Hum Genet. 2013;58:391-4. [PubMed: 23552673]
• Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature. 2017;549:519-22. [PubMed: 28959963]
• Khwaja A, Parnell SE, Ness K, Bompadre V, White KK. Opsismodysplasia: phosphate wasting osteodystrophy responds to bisphosphonate therapy. Front Pediatr. 2015;3:48. [PMC free article: PMC4476261] [PubMed: 26157786]
• Lee H, Nevarez L, Lachman RS, Wilcox WR, Krakow D, Cohn DH, University of Washington Center for Mendelian G. A second locus for Schneckenbecken dysplasia identified by a mutation in the gene encoding inositol polyphosphate phosphatase-like 1 (INPPL1). Am J Med Genet A. 2015;167A:2470-3. [PMC free article: PMC5036935] [PubMed: 25997753]
• Li B, Krakow D, Nickerson DA, Bamshad MJ, University of Washington Center for Mendelian G, Chang Y, Lachman RS, Yilmaz A, Kayserili H, Cohn DH. Opsismodysplasia resulting from an insertion mutation in the SH2 domain, which destabilizes INPPL1. Am J Med Genet A. 2014;164A:2407-11. [PMC free article: PMC4134718] [PubMed: 24953221]
• Nishimura G, Nakashima E, Hirose Y, Cole T, Cox P, Cohn DH, Rimoin DL, Lachman RS, Miyamoto Y, Kerr B, Unger S, Ohashi H, Superti-Furga A, Ikegawa S. The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type. J Med Genet. 2007;44:e73. [PMC free article: PMC2598034] [PubMed: 17400792]
• Rautengarten C, Quarrell OW, Stals K, Caswell RC, De Franco E, Baple E, Burgess N, Jokhi R, Heazlewood JL, Offiah AC, Ebert B, Ellard S. A hypomorphic allele of SLC35D1 results in Schneckenbecken-like dysplasia. Hum Mol Genet. 2019;28:3543-51. [PMC free article: PMC6927460] [PubMed: 31423530]
• 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, et al. 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]
• 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]
• Savarirayan R, Tunkel DE, Sterni LM, Bober MB, Cho TJ, Goldberg MJ, Hoover-Fong J, Irving M, Kamps SE, Mackenzie WG, Raggio C, Spencer SA, Bompadre V, White KK, on behalfof the Skeletal Dysplasia Management C. Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia. Orphanet J Rare Dis. 2021;16:31. [PMC free article: PMC7809733] [PubMed: 33446226]
• Silveira KC, Kanazawa TY, Silveira C, Lacarrubba-Flores MDJ, Carvalho BS, Cavalcanti DP. Molecular diagnosis in a cohort of 114 patients with rare skeletal dysplasias. Am J Med Genet C Semin Med Genet. 2021;187:396-408. [PubMed: 34529350]
• 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®): optimizing its use in a clinical diagnostic or research setting. Hum Genet. 2020;139:1197-207. [PMC free article: PMC7497289] [PubMed: 32596782]
• Unger S, Antoniazzi F, Brugnara M, Alanay Y, Caglayan A, Lachlan K, Ikegawa S, Nishimura G, Zabel B, Spranger J, Superti-Furga A. Clinical and radiographic delineation of odontochondrodysplasia. Am J Med Genet A. 2008;146A:770-8. [PubMed: 18241073]
• 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 A. 2023;191:1164-209. [PMC free article: PMC10081954] [PubMed: 36779427]
• White KK, Bober MB, Cho TJ, Goldberg MJ, Hoover-Fong J, Irving M, Kamps SE, Mackenzie WG, Raggio C, Spencer SA, Bompadre V, Savarirayan R; Skeletal Dysplasia Management C. Best practice guidelines for management of spinal disorders in skeletal dysplasia. Orphanet J Rare Dis. 2020;15:161. [PMC free article: PMC7313125] [PubMed: 32580780]
• White KK, Bompadre V, Goldberg MJ, Bober MB, Cho TJ, Hoover-Fong JE, Irving M, Mackenzie WG, Kamps SE, Raggio C, Redding GJ, Spencer SS, Savarirayan R, Theroux MC, Skeletal Dysplasia Management C. Best practices in peri-operative management of patients with skeletal dysplasias. Am J Med Genet A. 2017;173:2584-95. [PubMed: 28763154]
• Yeter B, Dilruba Aslanger A, Yeşil G, Elçioğlu NH. A novel mutation in the TRIP11 gene: diagnostic approach from relatively common skeletal dysplasias to an extremely rare odontochondrodysplasia. J Clin Res Pediatr Endocrinol. 2022;14:475-80. [PMC free article: PMC9724053] [PubMed: 34111908]
• Zeger MD, Adkins D, Fordham LA, White KE, Schoenau E, Rauch F, Loechner KJ. Hypophosphatemic rickets in opsismodysplasia. J Pediatr Endocrinol Metab. 2007;20:79-86. [PubMed: 17315533]