Mccune Albright Syndorme/Craniofacial Fibrous Dysplasia and Postcraniectomy Syndrome: Case Report and Literature Review

   

Jefferson Arce Tovar¹, Erick E Muñoz Rodríguez^2*, Jhonier Osorio Valencia³, Daniela Toro³ and Luis F Duarte Correales⁴

Citation: Tovar AJ, Rodriguez MEE, Valencia JO, Toro D, Duarte Correales LF. (2022) Mccune Albright Syndorme/Craniofacial Fibrous Dysplasia and Postcraniectomy Syndrome: Case Report and Literature Review. Adv Clin Med Res. 4(1):1-13.

Received: November 8, 2022 | Published: January 15, 2023

Copyright^© 2023 genesis pub by Tovar JA, et al. CC BY-NC-ND 4.0 DEED. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License.,This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation.

DOI: https://doi.org/10.52793/ACMR.2023.4(1)-46

Abstract

Introduction: McCune Albright syndrome (MAS) is a rare pathology caused by a genetic mutation of the GNAS1 gene that causes fibrous dysplasia (FD) among other endocrinological and metabolic manifestations. Here is presented a case report, in which craniofacial dysplasia (CFFD) produces functional alteration, its treatment, and the management of underlying complications.

Case Report: A 10-year-old female patient who presented with CFD with progressive involvement of the orbital cavity, compression of the optic nerve and right oculomotor cranial nerves, associated with precocious puberty and the appearance of ‘’café-au-lait’’ spots on the skin. ', finally, the diagnosis of MAS is made. Right front-parieto-temporal craniectomy and intra canalicular decompression of the optic nerve was performed getting partial improvement of functional alteration. Subsequently, cranioplasty is performed to manage post craniectomy/trephined syndrome.

Discussion: MAS is a genetic postzygotic disease that occurs in early stages of embryonic development, which explains its mosaicism. Among its manifestation is FD, which is explained by the hyperfunctioning nature of the mutation. In the case of DCF, continuous surveillance is required by a multidisciplinary team that includes a neurosurgeon, whose intervention is reserved for cases in which functional alterations occur, following the recommendations given by medical literature regarding the approach and type of surgery. Decompressive craniectomy can be associated with complications such as post craniectomy/trephined syndrome, which shows improvement or resolution with cranioplasty.

Conclusion: The diagnosis of MAS is clinical, and its mosaicism is explained by its early presentation in embryonic development. In the case of FCD with functional compromise, neurosurgical intervention is required, seeking the recovery and preservation of the compromised cranial nerves, avoiding prophylactic decompressions. In case of complications such as postcraniectomy/trephination syndrome, timely cranioplasty should be performed as it turns out to be highly effective as a treatment, however, the need for studies aimed at its characterization and diagnosis arises.

Keywords

McCune albright syndrome; Fibrous dysplasia; Craniofacial fibrous dysplasia; Craniofacial surgery; Post craniectomy syndrome; Trephined syndrome; Cranioplasty

Introduction

McCune Albright syndrome is a rare pathology caused by a post zygotic genetic mutation of the GNAS1 gene that classically causes FD, hyper functioning endocrinepathies and ‘’café-au-lait’’ spots on the skin, that make up the classic triad of its presentation, although, other hormonal and metabolic alterations are currently described. Despite its infrequency, it is a condition that represents a challenge for the multidisciplinary team that must evaluate it, which includes the neurosurgeon or craniofacial surgeon when CFFD is present, so is necessary to know the recommendations and advances regarding available interventions. Likewise, the description and understanding of complications that, although rare, may occur after a craniectomy, such as post craniectomy/trephined syndrome, is required. We conducted a review of the literature regarding the report of a case of MAS with polyostotic FD, with functional complications that required de-compressive surgical management and cranioplasty was subsequently performed to manage post-craniectomy syndrome.

Case Report

A 10-year-old female patient with a history of right frontal mild cranioencephalic trauma (MCET) who consulted 3 years later for a new MCET in the same anatomical region with evidence of front-orbital growth, in whom right upper frontal hyperostotic reaction is considered. The mother reports the larche, pubarche and apocrine odor since she was 8 years old. Physical examination reveals right frontal deformity associated with ipsilateral palpebral ptosis. Additionally, in a radiological study by simple skull computed tomography (SSCT), right front sphenoidal FD is found. Late outpatient follow-up is performed due to the Sars-Cov-2 pandemic, on clinical examination, facial asymmetry with right frontal protrusion and exophthalmos is found; visual alteration with mydriatic pupil, poor response to the direct and consensual photo motor reflexes, paresis of the IV and VI cranial nerves and partial optic atrophy with temporary pallor of the nerve, accompanied by visual acuity deterioration that progresses to amauros is, confirmed by visual campimetry. In addition, there is evidence of the appearance of ‘’café au lait’’ spots on the abdomen (Figure 1). A new SSCT with 3D reconstruction and magnetic resonance imaging (MRI) shows that the right FD progresses until it partially compromises the optic nerve and the facial and orbital cavity symmetry (Figure 2-3).

Figure 1: Abdomen’sphotograph thatshows a single café-au-lait macule on skin.

 

Figure 2: SSCT with 3D reconstruction. A) Superior view of the 3D reconstruction showing bone protrusion in the right frontal region that compromises facial symmetry. B) Front view showing compromised symmetry of the right orbital cavity. C) Axial SSCT slice showing obstruction and occupation of the right orbital cavity by dysplastic tissue. D) Sagittal slice with right frontoethmoidal bone expansion, with changes in bone density suggestive of fibrous dysplasia.

 

Figure 3: Brain MRI. A) Axial slice T1 sequence showing dysplastic tissue compromising orbital cavity. B) Sagittal T2 slice with right frontoethmoid sphenoid fibrous dysplasia and partial involvement of the right optic nerve.

Admission to an intermediate care unit is considered due to the risk of progressive intracranial hypertension. In laboratories there is evidence of vitamin D deficiency and hydroelectrolytic disorder. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, idiopathic central puberty, and the possibility of a syndromic origin. Considering polyostotic FD of craniofacial location, precocious puberty, café-au-lait spots and derived metabolic disorders, the diagnosis of McCune Albright syndrome is made.

Vitamin D supplement 2000 IU/day, calcium carbonate 1200 mg/day and start of pubertal brake with gonadotropin-releasing hormone analog (GNRH), triptorelin pamoate 11.25 mg in joint assessment by neurosurgery and pediatric endocrinology are indicated. Due to CFFD, right frontoparietotemporal de-compressive craniectomy with intra canalicular decompression of the optic nerve is considered. Surgical findings include right frontal-parietal bone dysplasia, intracranial hypertension, as well as compressed right orbital fissure and optic canal. After the intervention, improvement of cranial nerve alterations is observed without alteration of neurological status, for that reason it is considered discharge.

One year after the decompressive craniectomy, she consulted for high-intensityoppressive headache in the right parietal region, associated with ipsilateral eye pain, dizziness, and nausea. Physical examination reveals a right cranial bone defect and palpebral ptosis on the same side. Due to a history of extensive craniectomy and the appearance of neurological symptoms, she is considered to have post-craniectomy syndrome and is hospitalized. Therapy with bisphosphonates (zoledronic acid) and ionic and vitamin D supplementation is started due levels are found to be below the normal limit. Heterologous graft cranioplasty is performed without complications, with improvement of the symptoms for which she was admitted (Figure 4).

Figure 4: Axial SSCT showing bone defect prior to cranioplasty, without radiological evidence of intracranial pressure alteration. B) 3D reconstruction by computed tomography showing bone defect with small foci of dysplasia.

Discussion

Etiology and Pathophysiology

In MAS there is an increased activity of Gs protein signaling, caused by an acquired somatic gain-of-function mutation in the GNAS gene encoding its alpha subunit. G protein coupled receptors (GPCRs) participate in multiple cellular pathways, including some that have been identified as regulators of osteoblast formation and function, influencing bone formation and homeostasis[2-3]. The most accepted models and theories affirm that the mutation is postzygotic, explaining the mosaicism that characteizes the disease, also justified by the ubiquity of the protein in the affected tissues, making the range of extension and severity of its manifestation variable [2-3]. In addition, the time in which the genetic alteration occurs also explains its non-hereditary nature, due it does not compromise the germ line[2]. The involvement of tissues of the three germ layers suggests the appearance of the mutation in early stages of embryonic development, supported by models in which the alteration presents in a pluripotent stem cell ends up affecting a wide variety of tissues, resulting in the phenotype of the syndrome depends on the cell type, number of affected cells, their viability, and epigenetic factors. This variable expression also influences on the severity of the disease, leading to earlier mutations, greater extension of the disease[1-4].

Molecular-level changes include inhibition of GTPase activity and persistent stimulation of adenylate cyclase, causing persistently elevated intracellular levels of cyclic AMP and dysregulation of signaling, a consequence of specific amino acid substitution in the GTP hydrolase domain ofGs alpha subunit[2-5]. As a result of the mutation, normal bone is replaced by structurally defective osteofibrous tissue, in addition to the compromise of the hematopoietic bone marrow in relation to the affected site. Histologically, fibrous tissue is characterized by the presence of fibroblasts that express markers of early stages of osteogenic maturation, suggesting dysregulation in the differentiation of osteogenic progenitors to mature bone cells, resulting in the production of excessive amounts of abnormal bone matrix [6].  It has been found that tissue samples with FD produce elevated basal levels of IL-6, a cytokine that mediates osteoclastogenesis, causing increased bone resorption in the affected bone [4-6]. The endocrine pathways in which the signaling of their hormones and receptor proteins are ligand-dependent, such as LH, FSH, TSH, GHRH and ACTH, show hyperfunction, resulting in the characteristic endocrinological alterations of the syndrome [7-8].

Diagnosis

Clinical suspicion of this syndrome is based on the presence of FD and one or more extraskeletal characteristics of the disease; or the presentation of two or more manifestations of the entity other than FD [1] (Figure 5,6). FD is defined by the finding of expansive bone lesions that lead to fragility, malformations, and pain. Once suspected, an exhaustive evaluation is carried out that will allow its definitive diagnosis and classification [3]. Considering the extension of the skeletal lesion, there is a monostotic form in which the alteration is present in a single anatomical site or point, and another in which it is present in more than one point without extra skeletal manifestations called polyostotic [1-3].

 

Figure 5: Intraoperative photograph of bone defect correction with heterologous graft.

Figure 6: Classic presentation of McCune Albright syndrome.

The extraskeletal manifestations described for the diagnosis of MAS include:

1. Café-au-lait macules on ''Café-au-lait'' skin: jagged and irregular edges, respect the midline.
2. Gonadotropin-independent sex steroid production leading to precocious puberty causing, in addition:

• In girls, recurrent follicular cysts, alterations in menstrual bleeding.
• In boys, testicular lesions with or without precocious puberty due to autonomous testosterone production.

3. Thyroid lesions with or without hyperthyroidism (non-autoimmune)
4. Excess growth hormone.
5. Neonatal hypercortisolism(1).

The presence of intramuscular myxomas is also considered a manifestation, which denotes Mazabraud syndrome [1]. There are cases where hypophosphatemia mediated by Fibroblast Growth Factor 23 (FGF-23) occurs, which is not considered a manifestation of the syndrome, but rather a marker of the severity of FD. The diagnosis of the syndrome is clinical, confirmed through laboratories aimed at evidencing hormonal and metabolic alterations. Molecular or histological confirmation is not required except in cases where there is doubt regarding the diagnosis or the initial analyzes are inconclusive [1-3]. There is a wide variety in the forms of radiological presentation, given the mosaicism that precedes the bone manifestations of the syndrome, in addition to the fact that its location varies between the axial skeleton, extremities and the skull. For the latter, the frequency of presentation of lesions shows the frontal bone as the most affected, followed by the sphenoid, ethmoid, parietal, temporal and occipital bones [5]. Bone expansion with the appearance of ground glass and deformities of the cranial vault leading to exophthalmos as the specific radiological characteristics of its involvement[9]. In addition, the presence of lesions with the appearance of extraosseous soft mass should be evaluated, due they suggest malignancy [1]. (Table 1) summarizes the usefulness of the studies radiological data available for the assessment of FD.

Radiological study	Utility
CT*	Evaluate nerve entrapment and optic nerve compression.
Three-dimensional bone reconstruction with helical CT	Optimal visualization of the extent of dysplastic bone in the skull base ·        Frosted glass pattern. ·        Homogeneously dense pattern. ·        Cystic variety.
MRI †	Image will depend on factors such as the number of bone trabeculae and degree of cellularity: Low intensity images with well-marked borders on T1 and T2.
SPECT ‡	Sensitive in detecting the edges of the DF