Polyostotic Fibrous Dysplasia With and Without McCune-Albright Syndrome-Clinical Features in a Nordic Pediatric Cohort.

Pauliina Utriainen,Outi Mäkitie,Sigridur Björnsdottir,Eva Horemuzova,Helena Valta

doi:10.3389/fendo.2018.00096

Abstract

Fibrous dysplasia (FD) presents as skeletal lesions in which normal bone is replaced by abnormal fibrous tissue due to mosaic GNAS mutation. McCune-Albright syndrome (MAS) refers to FD combined with skin (café-au-lait) and endocrine manifestations. This study describes the clinical childhood manifestations of polyostotic FD and MAS in a Nordic cohort. We retrospectively reviewed a cohort of pediatric patients (n = 16) with polyostotic FD with or without MAS diagnosed and followed in two Nordic Pediatric tertiary clinics between 1996 and 2017. Half of the 16 patients with polyostotic FD presented with MAS. All patients with MAS (n = 8) had café-au-lait spots, and either gonadotropin-independent precocious puberty (PP) (girls; n = 5) or abnormal testicle structure (boys, n = 3). None manifested hyperthyroidism or growth hormone excess. Mild hypophosphatemia was common (11/16), but none had signs of hypophosphatemic rickets. Craniofacial bone involvement was found in 12 patients (75%); in 5 of these, skeletal lesions were limited to craniofacial area. One child with craniofacial disease had lost vision due to optic nerve damage. Eleven (69%) patients had sustained a fracture at FD lesion, over half of them requiring surgical fixation of the fracture, most commonly in the proximal femur. The first symptoms leading to FD/MAS diagnosis included skull/facial asymmetry (n = 4), PP (n = 3), abnormal gait (n = 3), pathologic fracture (n = 3), wide-spread café-au-lait spots (n = 1), headache (n = 1), and vision loss (n = 1). Polyostotic FD and MAS remain diagnostic and therapeutic challenges because of the broad clinical spectrum. Recurrent fractures, pain, and even vision loss may impair the quality of life in children with FD.

Highlights

Fibrous dysplasia (FD) is a genetic, non-inheritable skeletal disorder in which normal bone is replaced by abnormal bone structure in the dysplastic FD lesions [1]
FD is caused by somatic activating mutation in the GNAS gene, coding for the α-subunit of the stimulatory G protein (Gs) [2, 3]
Caused by growth hormone (GH) excess is rather common manifestation in McCune–Albright syndrome (MAS) [9]

Summary

Introduction

Fibrous dysplasia (FD) is a genetic, non-inheritable skeletal disorder in which normal bone is replaced by abnormal bone structure in the dysplastic FD lesions [1]. FD is caused by somatic activating mutation in the GNAS gene, coding for the α-subunit of the stimulatory G protein (Gs) [2, 3] These assumingly postzygotic missense mutations cause genetic mosaicism and lead to constitutional activation of cAMP regulating Gsα in the affected cells [1, 3]. While café-au-lait spots are typically the earliest extra-skeletal manifestation in MAS, the most common endocrine manifestations include precocious puberty (PP), hyperthyroidism, and renal phosphate wasting with or without rickets/osteomalacia [7, 8]. According to the clinical definition by Collins and coworkers, the phenotype of MAS can include any combination of skeletal, skin, and endocrine features [1]. The original and stricter definition of MAS, which is still sometimes used [10, 11], requires the presence of all three manifestations—skeletal, skin, and endocrine—for diagnosis

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