Prevalence of Chiari malformation type 1 is increased in pseudohypoparathyroidism type 1A and associated with aberrant bone development
Neetu Krishnan, Patrick McMullan, Qingfen Yang, Alexzandrea N Buscarello, Emily L Germain-Lee, Neetu Krishnan, Patrick McMullan, Qingfen Yang, Alexzandrea N Buscarello, Emily L Germain-Lee
Abstract
Background: Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivating mutations in GNAS. Patients with maternally-inherited mutations develop pseudohypoparathyroidism type 1A (PHP1A) with multi-hormone resistance and aberrant craniofacial and skeletal development among other abnormalities. Chiari malformation type 1 (CM1), a condition in which brain tissue extends into the spinal canal when the skull is too small, has been reported in isolated cases of PHP1A. It has been hypothesized to be associated with growth hormone (GH) deficiency. Given the adverse clinical sequelae that can occur if CM1 goes unrecognized, we investigated the previously undetermined prevalence of CM1, as well as any potential correlations with GH status, given the known increased prevalence of GH deficiency in PHP1A. We also investigated these metrics for low lying cerebellar tonsils (LLCT), defined as tonsillar descent less than 5 mm below the foramen magnum. In addition, we investigated possible correlations of CM1/LLCT with advanced hand/wrist bone ages and craniofacial abnormalities known to occur in PHP1A to determine whether premature chondrocyte differentiation and/or aberrant craniofacial development could be potential etiologies of CM1/LLCT through both human studies and investigations of our AHO mouse model.
Methods: We examined patients with PHP1A in our clinic and noticed CM1 more frequently than expected. Therefore, we set out to determine the true prevalence of CM1 and LLCT in a cohort of 54 mutation-confirmed PHP1A participants who had clinically-indicated brain imaging. We examined potential correlations with GH status, clinical features, biological sex, genotype, and hand/wrist bone age determinations. In addition, we investigated the craniofacial development in our mouse model of AHO (Gnas E1+/-m) by histologic analyses, dynamic histomorphometry, and micro-computerized tomographic imaging (MCT) in order to determine potential etiologies of CM1/LLCT in PHP1A.
Results: In our cohort of PHP1A, the prevalence of CM1 is 10.8%, which is at least 10-fold higher than in the general population. If LLCT is included, the prevalence increases to 21.7%. We found no correlation with GH status, biological sex, genotype, or hand/wrist bone age. Through investigations of our Gnas E1+/-m mice, the correlate to PHP1A, we identified a smaller cranial vault and increased cranial dome angle with evidence of hyperostosis due to increased osteogenesis. We also demonstrated that there was premature closure of the spheno-occipital synchondrosis (SOS), a cartilaginous structure essential to the development of the cranial base. These findings lead to craniofacial abnormalities and could contribute to CM1 and LLCT development in PHP1A.
Conclusion: The prevalence of CM1 is at least 10-fold higher in PHP1A compared to the general population and 20-fold higher when including LLCT. This is independent of the GH deficiency that is found in approximately two-thirds of patients with PHP1A. In light of potential serious consequences of CM1, clinicians should have a low threshold for brain imaging. Investigations of our AHO mouse model revealed aberrant cranial formation including a smaller cranium, increased cranial dome angle, hyperostosis, and premature SOS closure rates, providing a potential etiology for the increased prevalence of CM1 and LLCT in PHP1A.
Conflict of interest statement
The authors have declared that no competing interests exist.
Copyright: © 2023 Krishnan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Figures
References
- Plagge A, Kelsey G, Germain-Lee EL. Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse. J Endocrinol. 2008;196(2):193–214. doi: 10.1677/JOE-07-0544
- Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Usardi A, et al.. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol. 2018;14(8):476–500. doi: 10.1038/s41574-018-0042-0
- Linglart A, Levine MA, Juppner H. Pseudohypoparathyroidism. Endocrinol Metab Clin North Am. 2018;47(4):865–88. doi: 10.1016/j.ecl.2018.07.011
- Germain-Lee EL. Management of pseudohypoparathyroidism. Curr Opin Pediatr. 2019;31(4):537–49. doi: 10.1097/MOP.0000000000000783
- Haldeman-Englert CR, Hurst ACE, Levine MA. Disorders of GNAS Inactivation. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, et al., editors. GeneReviews((R)). Seattle (WA). 2022.
- Davies SJ, Hughes HE. Imprinting in Albright’s hereditary osteodystrophy. J Med Genet. 1993;30(2):101–3. doi: 10.1136/jmg.30.2.101
- Levine MA, Downs RW Jr., Moses AM, Breslau NA, Marx SJ, Lasker RD, et al.. Resistance to multiple hormones in patients with pseudohypoparathyroidism. Association with deficient activity of guanine nucleotide regulatory protein. Am J Med. 1983;74(4):545–56. doi: 10.1016/0002-9343(83)91008-2
- Albright F B C, Smith P. Pseudohypoparathyroidism: an example of “Seabright-Bantam syndrome”. Endocrinology. 1942;30:922–32.
- Germain-Lee EL. Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type 1a. Pediatr Endocrinol Rev. 2006;3 Suppl 2:318–27.
- Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Ahmed SF, et al.. Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients. Horm Res Paediatr. 2020;93(3):182–96. doi: 10.1159/000508985
- Schlund M, Depeyre A, Kohler F, Nicot R, Ferri J. Cranio-Maxillofacial and Dental Findings in Albright’s Hereditary Osteodystrophy and Pseudohypoparathyroidism. Cleft Palate Craniofac J. 2019;56(6):831–6. doi: 10.1177/1055665618814661
- Le Norcy E, Reggio-Paquet C, de Kerdanet M, Mignot B, Rothenbuhler A, Chaussain C, et al.. Dental and craniofacial features associated with GNAS loss of function mutations. Eur J Orthod. 2020;42(5):525–33. doi: 10.1093/ejo/cjz084
- Germain-Lee EL, Ding CL, Deng Z, Crane JL, Saji M, Ringel MD, et al.. Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. Biochem Biophys Res Commun. 2002;296(1):67–72. doi: 10.1016/s0006-291x(02)00833-1
- Liu J, Erlichman B, Weinstein LS. The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. J Clin Endocrinol Metab. 2003;88(9):4336–41. doi: 10.1210/jc.2003-030393
- Mantovani G, Ballare E, Giammona E, Beck-Peccoz P, Spada A. The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads. J Clin Endocrinol Metab. 2002;87(10):4736–40. doi: 10.1210/jc.2002-020183
- Namnoum AB, Merriam GR, Moses AM, Levine MA. Reproductive dysfunction in women with Albright’s hereditary osteodystrophy. J Clin Endocrinol Metab. 1998;83(3):824–9. doi: 10.1210/jcem.83.3.4652
- Germain-Lee EL, Groman J, Crane JL, Jan de Beur SM, Levine MA. Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. J Clin Endocrinol Metab. 2003;88(9):4059–69. doi: 10.1210/jc.2003-030028
- Mantovani G, Maghnie M, Weber G, De Menis E, Brunelli V, Cappa M, et al.. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene. J Clin Endocrinol Metab. 2003;88(9):4070–4. doi: 10.1210/jc.2002-022028
- Albright FA, Henneman P. Pseudo-pseudohypoparathyroidism. Trans Assoc Am Physicians 1952;65:337–50.
- Long DN, McGuire S, Levine MA, Weinstein LS, Germain-Lee EL. Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab. 2007;92(3):1073–9. doi: 10.1210/jc.2006-1497
- Hayward BE, Kamiya M, Strain L, Moran V, Campbell R, Hayashizaki Y, et al.. The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proc Natl Acad Sci U S A. 1998;95(17):10038–43. doi: 10.1073/pnas.95.17.10038
- Germain-Lee EL, Schwindinger W, Crane JL, Zewdu R, Zweifel LS, Wand G, et al.. A mouse model of albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene. Endocrinology. 2005;146(11):4697–709. doi: 10.1210/en.2005-0681
- Weinstein LS, Yu S, Ecelbarger CA. Variable imprinting of the heterotrimeric G protein G(s) alpha-subunit within different segments of the nephron. Am J Physiol Renal Physiol. 2000;278(4):F507–14. doi: 10.1152/ajprenal.2000.278.4.F507
- Yu S, Yu D, Lee E, Eckhaus M, Lee R, Corria Z, et al.. Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the gsalpha gene. Proc Natl Acad Sci U S A. 1998;95(15):8715–20. doi: 10.1073/pnas.95.15.8715
- Long DN, Levine MA, Germain-Lee EL. Bone mineral density in pseudohypoparathyroidism type 1a. J Clin Endocrinol Metab. 2010;95(9):4465–75. doi: 10.1210/jc.2010-0498
- McMullan P, Maye P, Yang Q, Rowe DW, Germain-Lee EL. Parental Origin of Gsalpha Inactivation Differentially Affects Bone Remodeling in a Mouse Model of Albright Hereditary Osteodystrophy. JBMR Plus. 2022;6(1):e10570.
- McMullan P, Germain-Lee EL. Aberrant bone regulation in Albright hereditary osteodystrophy due to Gnas inactivation: mechanisms and translational implications. Curr Osteoporos Rep. 2021.
- H C. Ueber Veränderungen des Kleinhirns infolge von Hydrocephalie des Grosshirns. Dtsch Med Wochenschr. 1891:1172–5
- Tubbs RS, Cohen-Gadol AA. Hans Chiari (1851–1916). J Neurol. 2010;257(7):1218–20. doi: 10.1007/s00415-010-5529-0
- Aitken LA, Lindan CE, Sidney S, Gupta N, Barkovich AJ, Sorel M, et al.. Chiari type I malformation in a pediatric population. Pediatr Neurol. 2009;40(6):449–54. doi: 10.1016/j.pediatrneurol.2009.01.003
- Barkovich AJ, Wippold FJ, Sherman JL, Citrin CM. Significance of cerebellar tonsillar position on MR. AJNR Am J Neuroradiol. 1986;7(5):795–9.
- Dangouloff-Ros V, Roux CJ, Boulouis G, Levy R, Nicolas N, Lozach C, et al.. Incidental Brain MRI Findings in Children: A Systematic Review and Meta-Analysis. AJNR Am J Neuroradiol. 2019;40(11):1818–23. doi: 10.3174/ajnr.A6281
- Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, Krestin GP, et al.. Incidental findings on brain MRI in the general population. N Engl J Med. 2007;357(18):1821–8. doi: 10.1056/NEJMoa070972
- Sadler B, Kuensting T, Strahle J, Park TS, Smyth M, Limbrick DD, et al.. Prevalence and Impact of Underlying Diagnosis and Comorbidities on Chiari 1 Malformation. Pediatr Neurol. 2020;106:32–7.
- Naessig S, Kapadia BH, Para A, Ahmad W, Pierce K, Janjua B, et al.. Timing to surgery of Chiari malformation type 1 affects complication types: An analysis of 13,812 patients. J Craniovertebr Junction Spine. 2020;11(3):232–6. doi: 10.4103/jcvjs.JCVJS_67_20
- Langridge B, Phillips E, Choi D. Chiari Malformation Type 1: A Systematic Review of Natural History and Conservative Management. World Neurosurg. 2017;104:213–9. doi: 10.1016/j.wneu.2017.04.082
- Poretti A, Ashmawy R, Garzon-Muvdi T, Jallo GI, Huisman TA, Raybaud C. Chiari Type 1 Deformity in Children: Pathogenetic, Clinical, Neuroimaging, and Management Aspects. Neuropediatrics. 2016;47(5):293–307. doi: 10.1055/s-0036-1584563
- McClugage SG, Oakes WJ. The Chiari I malformation. J Neurosurg Pediatr. 2019;24(3):217–26. doi: 10.3171/2019.5.PEDS18382
- Epstein NE. Definitions and treatments for chiari-1 malformations and its variants: Focused review. Surg Neurol Int. 2018;9:152. doi: 10.4103/sni.sni_208_18
- Furuya K, Sano K, Segawa H, Ide K, Yoneyama H. Symptomatic tonsillar ectopia. J Neurol Neurosurg Psychiatry. 1998;64(2):221–6. doi: 10.1136/jnnp.64.2.221
- Arnett BC. Tonsillar ectopia and headaches. Neurol Clin. 2004;22(1):229–36. doi: 10.1016/S0733-8619(03)00101-4
- Borcek AO, Aslan A. Unexpected Progression of Tonsillar Herniation in Two Pediatric Cases with Chiari Malformation Type I and Review of the Literature. Pediatr Neurosurg. 2019;54(1):51–6. doi: 10.1159/000495066
- Milhorat TH, Chou MW, Trinidad EM, Kula RW, Mandell M, Wolpert C, et al.. Chiari I malformation redefined: clinical and radiographic findings for 364 symptomatic patients. Neurosurgery. 1999;44(5):1005–17. doi: 10.1097/00006123-199905000-00042
- Dagtekin A, Avci E, Kara E, Uzmansel D, Dagtekin O, Koseoglu A, et al.. Posterior cranial fossa morphometry in symptomatic adult Chiari I malformation patients: comparative clinical and anatomical study. Clin Neurol Neurosurg. 2011;113(5):399–403. doi: 10.1016/j.clineuro.2010.12.020
- Fric R, Eide PK. Chiari type 1-a malformation or a syndrome? A critical review. Acta Neurochir (Wien). 2020;162(7):1513–25. doi: 10.1007/s00701-019-04100-2
- Nair BR, Rajshekhar V. Posterior fossa morphometry in 170 South Asian children and adults with Chiari malformation and its correlation with tonsillar descent. Br J Neurosurg. 2021:1–8. doi: 10.1080/02688697.2021.2008873
- Hamilton J, Blaser S, Daneman D. MR imaging in idiopathic growth hormone deficiency. AJNR Am J Neuroradiol. 1998;19(9):1609–15.
- Marwaha R, Menon PS, Jena A, Pant C, Sethi AK, Sapra ML. Hypothalamo-pituitary axis by magnetic resonance imaging in isolated growth hormone deficiency patients born by normal delivery. J Clin Endocrinol Metab. 1992;74(3):654–9. doi: 10.1210/jcem.74.3.1740501
- Nishikawa M, Sakamoto H, Hakuba A, Nakanishi N, Inoue Y. Pathogenesis of Chiari malformation: a morphometric study of the posterior cranial fossa. J Neurosurg. 1997;86(1):40–7. doi: 10.3171/jns.1997.86.1.0040
- Urbizu A, Poca MA, Vidal X, Rovira A, Sahuquillo J, Macaya A. MRI-based morphometric analysis of posterior cranial fossa in the diagnosis of chiari malformation type I. J Neuroimaging. 2014;24(3):250–6. doi: 10.1111/jon.12007
- Bernard S, Loukas M, Rizk E, Oskouian RJ, Delashaw J, Tubbs RS. The human occipital bone: review and update on its embryology and molecular development. Childs Nerv Syst. 2015;31(12):2217–23. doi: 10.1007/s00381-015-2870-8
- Goldstein JA, Paliga JT, Wink JD, Bartlett SP, Nah HD, Taylor JA. Earlier evidence of spheno-occipital synchondrosis fusion correlates with severity of midface hypoplasia in patients with syndromic craniosynostosis. Plast Reconstr Surg. 2014;134(3):504–10. doi: 10.1097/PRS.0000000000000419
- Wei X, Hu M, Mishina Y, Liu F. Developmental Regulation of the Growth Plate and Cranial Synchondrosis. J Dent Res. 2016;95(11):1221–9. doi: 10.1177/0022034516651823
- Loukas M, Shayota BJ, Oelhafen K, Miller JH, Chern JJ, Tubbs RS, et al.. Associated disorders of Chiari Type I malformations: a review. Neurosurg Focus. 2011;31(3):E3. doi: 10.3171/2011.6.FOCUS11112
- Tubbs RS, Wellons JC 3rd, Smyth MD, Bartolucci AA, Blount JP, Oakes WJ, et al.. Children with growth hormone deficiency and Chiari I malformation: a morphometric analysis of the posterior cranial fossa. Pediatr Neurosurg. 2003;38(6):324–8. doi: 10.1159/000070416
- Tubbs RS, Wellons JC 3rd, Oakes WJ, Blount JP. Reformation of the posterior atlanto-occipital membrane following posterior fossa decompression with subsequent constriction at the craniocervical junction. Pediatr Neurosurg. 2003;38(4):219–21. doi: 10.1159/000069092
- Kashani P, Roy M, Gillis L, Ajani O, Samaan MC. The Association of Pseudohypoparathyroidism Type Ia with Chiari Malformation Type I: A Coincidence or a Common Link? Case Rep Med. 2016;2016:7645938. doi: 10.1155/2016/7645938
- Martinez-Lage JF, Guillen-Navarro E, Lopez-Guerrero AL, Almagro MJ, Cuartero-Perez B, de la Rosa P. Chiari type 1 anomaly in pseudohypoparathyroidism type Ia: pathogenetic hypothesis. Childs Nerv Syst. 2011;27(12):2035–9. doi: 10.1007/s00381-011-1606-7
- Visconti P, Posar A, Scaduto MC, Russo A, Tamburrino F, Mazzanti L. Neuropsychiatric phenotype in a child with pseudohypoparathyroidism. J Pediatr Neurosci. 2016;11(3):267–70. doi: 10.4103/1817-1745.193373
- Poon SW, Chung BH, Tsang AM, Poon GW. Headache in a Child with Pseudohypoparathyroidism: An Alarming Symptom Not to Miss. Case Rep Endocrinol. 2020;2020:8840082. doi: 10.1155/2020/8840082
- Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994;125(1):29–35. doi: 10.1016/s0022-3476(94)70117-2
- Steinbach HL, Young DA. The roentgen appearance of pseudohypoparathyroidism (PH) and pseudo-pseudohypoparathyroidism (PPH). Differentiation from other syndromes associated with short metacarpals, metatarsals, and phalanges. Am J Roentgenol Radium Ther Nucl Med. 1966;97(1):49–66. doi: 10.2214/ajr.97.1.49
- Fitch N. Albright’s hereditary osteodystrophy: a review. Am J Med Genet. 1982;11(1):11–29. doi: 10.1002/ajmg.1320110104
- Sakamoto A, Chen M, Kobayashi T, Kronenberg HM, Weinstein LS. Chondrocyte-specific knockout of the G protein G(s)alpha leads to epiphyseal and growth plate abnormalities and ectopic chondrocyte formation. J Bone Miner Res. 2005;20(4):663–71. doi: 10.1359/JBMR.041210
- Bastepe M, Weinstein LS, Ogata N, Kawaguchi H, Juppner H, Kronenberg HM, et al.. Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo. Proc Natl Acad Sci U S A. 2004;101(41):14794–9. doi: 10.1073/pnas.0405091101
- Kobayashi T, Soegiarto DW, Yang Y, Lanske B, Schipani E, McMahon AP, et al.. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest. 2005;115(7):1734–42. doi: 10.1172/JCI24397
- Salemi P, Skalamera Olson JM, Dickson LE, Germain-Lee EL. Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype, Inheritance, Sex, Age, Hormonal Status, and BMI. J Clin Endocrinol Metab. 2018;103(1):158–68. doi: 10.1210/jc.2017-00860
- Huso DL, Edie S, Levine MA, Schwindinger W, Wang Y, Juppner H, et al.. Heterotopic ossifications in a mouse model of albright hereditary osteodystrophy. PLoS One. 2011;6(6):e21755. doi: 10.1371/journal.pone.0021755
- Aboulezz AO, Sartor K, Geyer CA, Gado MH. Position of cerebellar tonsils in the normal population and in patients with Chiari malformation: a quantitative approach with MR imaging. J Comput Assist Tomogr. 1985;9(6):1033–6. doi: 10.1097/00004728-198511000-00005
- Maghnie M, Cavigioli F, Tinelli C, Autelli M, Arico M, Aimaretti G, et al.. GHRH plus arginine in the diagnosis of acquired GH deficiency of childhood-onset. J Clin Endocrinol Metab. 2002;87(6):2740–4. doi: 10.1210/jcem.87.6.8546
- Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, et al.. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab. 1996;81(9):3323–7. doi: 10.1210/jcem.81.9.8784091
- Gil-Ad I, Topper E, Laron Z. Oral clonidine as a growth hormone stimulation test. Lancet. 1979;2(8137):278–9. doi: 10.1016/s0140-6736(79)90293-9
- Sizonenko PC, Clayton PE, Cohen P, Hintz RL, Tanaka T, Laron Z. Diagnosis and management of growth hormone deficiency in childhood and adolescence. Part 1: diagnosis of growth hormone deficiency. Growth Horm IGF Res. 2001;11(3):137–65. doi: 10.1054/ghir.2001.0203
- AACE clinical practice guidelines for growth hormone use in adults and children. Endocr Pract. 1998;4:165–73.
- Allen DKD, Biller B, Cueno R, Bengtsson B-A, Melmed S, Blethen S, et al.. The diagnosis and management of adult hormone deficiency. Clinical Courier. 1998;16:1–12.
- Gruelich WW PS. Radiographic atlas of skeletal development of the hand and wrist. Stanford, CA Stanford University Press; 1993.
- Mantovani G, Bondioni S, Locatelli M, Pedroni C, Lania AG, Ferrante E, et al.. Biallelic expression of the Gsalpha gene in human bone and adipose tissue. J Clin Endocrinol Metab. 2004;89(12):6316–9. doi: 10.1210/jc.2004-0558
- Navein AE, Cooke EJ, Davies JR, Smith TG, Wells LH, Ohazama A, et al.. Disrupted mitochondrial function in the Opa3L122P mouse model for Costeff Syndrome impairs skeletal integrity. Hum Mol Genet. 2016;25(12):2404–16. doi: 10.1093/hmg/ddw107
- Muthukumar N, Swaminathan R, Venkatesh G, Bhanumathy SP. A morphometric analysis of the foramen magnum region as it relates to the transcondylar approach. Acta Neurochir (Wien). 2005;147(8):889–95. doi: 10.1007/s00701-005-0555-x
- Gocmen Mas N, Cirpan S, Aksu F, Yonguc Demirci GN, Lafci Fahrioglu S, Durmaz O, et al.. Comparison of Three Methods Used for Estimating Area of Foramen Magnum. J Craniofac Surg. 2018;29(3):792–5. doi: 10.1097/SCS.0000000000004250
- Cirpan S, Yonguc GN, Mas NG, Aksu F, Orhan Magden A. Morphological and Morphometric Analysis of Foramen Magnum: An Anatomical Aspect. J Craniofac Surg. 2016;27(6):1576–8. doi: 10.1097/SCS.0000000000002822
- Yotsumoto T, Morozumi N, Furuya M, Fujii T, Hirota K, Ueda Y, et al.. Foramen magnum stenosis and midface hypoplasia in C-type natriuretic peptide-deficient rats and restoration by the administration of human C-type natriuretic peptide with 53 amino acids. PLoS One. 2019;14(5):e0216340. doi: 10.1371/journal.pone.0216340
- Rigueur D, Lyons KM. Whole-mount skeletal staining. Methods Mol Biol. 2014;1130:113–21. doi: 10.1007/978-1-62703-989-5_9
- Dyment NA, Jiang X, Chen L, Hong SH, Adams DJ, Ackert-Bicknell C, et al.. High-Throughput, Multi-Image Cryohistology of Mineralized Tissues. J Vis Exp. 2016(115). doi: 10.3791/54468
- van ’t Hof RJ, Rose L, Bassonga E, Daroszewska A. Open source software for semi-automated histomorphometry of bone resorption and formation parameters. Bone. 2017;99:69–79. doi: 10.1016/j.bone.2017.03.051
- Zhou Y, Xin X, Wang L, Wang B, Chen L, Liu O, et al.. Senolytics improve bone forming potential of bone marrow mesenchymal stem cells from aged mice. NPJ Regen Med. 2021;6(1):34. doi: 10.1038/s41536-021-00145-z
- Stangroom J. P Value from Chi-Square Calculator: Social Science Statistics; [.
- Elli FM, Barbieri AM, Bordogna P, Ferrari P, Bufo R, Ferrante E, et al.. Screening for GNAS genetic and epigenetic alterations in progressive osseous heteroplasia: first Italian series. Bone. 2013;56(2):276–80. doi: 10.1016/j.bone.2013.06.015
- Nwotchouang BST, Eppelheimer MS, Ibrahimy A, Houston JR, Biswas D, Labuda R, et al.. Clivus length distinguishes between asymptomatic healthy controls and symptomatic adult women with Chiari malformation type I. Neuroradiology. 2020;62(11):1389–400. doi: 10.1007/s00234-020-02453-5
- Tubbs RS, Benzie AL, Rizk E, Chern JJ, Loukas M, Oakes WJ. Histological study of the occipital bone from patients with Chiari I malformation. Childs Nerv Syst. 2016;32(2):351–3. doi: 10.1007/s00381-015-2907-z
- Mamoei S, Cortnum S. Raised intracranial pressure as a result of pansynostosis in a child with Albright’s hereditary osteodystrophy. Childs Nerv Syst. 2017;33(5):865–8. doi: 10.1007/s00381-016-3330-9
- Xu R, Khan SK, Zhou T, Gao B, Zhou Y, Zhou X, et al.. Galphas signaling controls intramembranous ossification during cranial bone development by regulating both Hedgehog and Wnt/beta-catenin signaling. Bone Res. 2018;6:33.
- Lei R, Zhang K, Wei Y, Chen M, Weinstein LS, Hong Y, et al.. G-Protein alpha-Subunit Gsalpha Is Required for Craniofacial Morphogenesis. PLoS One. 2016;11(2):e0147535.
- Graul-Neumann LM, Bach A, Albani M, Ringe H, Weimann A, Kress W, et al.. Boy with pseudohypoparathyroidism type 1a caused by GNAS gene mutation (deltaN377), Crouzon-like craniosynostosis, and severe trauma-induced bleeding. Am J Med Genet A. 2009;149A(7):1487–93. doi: 10.1002/ajmg.a.32889
- Nie X. Cranial base in craniofacial development: developmental features, influence on facial growth, anomaly, and molecular basis. Acta Odontol Scand. 2005;63(3):127–35. doi: 10.1080/00016350510019847
- Nam HK, Sharma M, Liu J, Hatch NE. Tissue Nonspecific Alkaline Phosphatase (TNAP) Regulates Cranial Base Growth and Synchondrosis Maturation. Front Physiol. 2017;8:161. doi: 10.3389/fphys.2017.00161
- Mitra I, Duraiswamy M, Benning J, Joy HM. Imaging of focal calvarial lesions. Clin Radiol. 2016;71(4):389–98. doi: 10.1016/j.crad.2015.12.010
- Chotai S, Medhkour A. Surgical outcomes after posterior fossa decompression with and without duraplasty in Chiari malformation-I. Clin Neurol Neurosurg. 2014;125:182–8. doi: 10.1016/j.clineuro.2014.07.027
Source: PubMed