IllnessMcCune-Albright syndrome/Fibrous dysplasia, differential diagnosis

NGS +

McCune-Albright syndrome is a disorder that affects bone, skin and endocrine tissues. People with McCune-Albright syndrome develop polyostotic fibrous dysplasia in some bones, which can lead to fractures and uneven growth, often limited to one side of the body. In <1% of cases, these lesions may become cancerous. In addition, café-au-lait spots may be present from birth, sometimes on one side only. Girls may enter puberty (very) early, and both sexes can develop a goiter or thyroid nodules. Half of the patients present with hyperthyroidism, some show acromegaly and coarser facial features. Rarely, affected individuals exhibit signs of Cushing syndrome. McCune-Albright syndrome is caused by mutations in the GNAS gene. Constitutive activation of the encoded enzyme adenylate cyclase leads to hormonal overproduction. The disorder is caused by a somatic mutation in the GNAS gene at a very early stage of development leading to a cellular mosaic status. The severity of the disorder and the specific clinical features depend on the percentage and localization of the cells that share the mutated GNAS gene: Molecular genetic diagnostics must therefore be designed to be particularly sensitive. The disease is not passed on to the next generation. In the differential diagnosis, other mutated genes are considered besides GNAS that cause similar symptoms on skin and bone, such as cutaneous-skeletal hypophosphatemia syndrome, neurofibromatosis, fibroosseous skeletal lesions and cherubism.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK274564/

• DD: Fibröse Knochendysplasie, Café-au-lait-Flecken der Haut + Pubertas praecox
• Alias: Mazabraud syndrome (intramuscular myxomas fibrous dysplasia/McCune-Albright s.)
• Alias: Pubertas praecox, familiäre Gonadotropin-unabhängige weibliche
• Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Allelic: Bladder cancer, somatic (HRAS)
• Allelic: Colorectal cancer, somatic (NRAS)
• Allelic: Congenital myopathy with excess of muscle spindles (HRAS)
• Allelic: Costello syndrome (HRAS)
• Allelic: Epidermal nevus, somatic (NRAS)
• Allelic: Epilepsy idiopathic generalized, susceptibility to, 8 (CASR)
• Allelic: Failure of tooth eruption, primary (PTH1R)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (SQSTM1)
• Allelic: Leukemia, juvenile myelomonocytic (NF1)
• Allelic: Melanocytic nevus syndrome, congenital, somatic (NRAS)
• Allelic: Myopathy, distal, with rimmed vacuoles (SQSTM1)
• Allelic: Neurodegeneration with ataxia, dystonia + gaze palsy, childhood-onset (SQSTM1)
• Allelic: Nevus sebaceous or woolly hair nevus, somatic (HRAS)
• Allelic: Noonan syndrome 6 (NRAS)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: Osteolysis, familial expansile (TNFRNF11A)
• Allelic: Osteopetrosis, AR 7 (TNFRNF11A)
• Allelic: Pituitary adenoma 3, multiple types, somatic (GNAS)
• Allelic: Progressive osseous heteroplasia, inactivating heterozygous mutation (paternal GNAS)
• Allelic: Pseudohypoparathyroidism Ia, inactivating heterozygous mutation exon 1-12 (maternal GNAS)
• Allelic: Pseudohypoparathyroidism Ib, imprinting defect-heterozygous del. reg. elements (mat. GNAS)
• Allelic: Pseudohypoparathyroidism Ic, inactivating heterozygous mutation exon 13 (maternal GNAS)
• Allelic: Pseudopseudohypoparathyroidism, inactivating heterozygous mutation (paternal GNAS)
• Allelic: RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic (NRAS)
• Allelic: Spitz nevus or nevus spilus, somatic (HRAS)
• Allelic: Thyroid carcinoma, follicular, somatic (HRAS, NRAS)
• Cherubism (SH3BP2)
• Chondrodysplasia, Blomstrand type (PTH1R)
• Cutaneous-skeletal hypophosphatemia syndrome (HRAS, NRAS)
• Eiken syndrome (PTH1R)
• Hyperparathyroidism, neonatal 239200 AD, AR 3
• Hypocalcemia, AD (CASR)
• Hypocalcemia, AD, with Bartter syndrome (CASR)
• Hypocalciuric hypercalcemia, type I (CASR)
• Maffucci syndrome [panelapp] (IDH1)
• McCune-Albright syndrome, somatic, mosaic (GNAS)
• Metaphyseal chondrodysplasia, Murk Jansen type (PTH1R)
• Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria [panelapp] (IDH1)
• Neurocutaneous melanosis, somatic (NRAS)
• Neurofibromatosis, familial spinal (NF1)
• Neurofibromatosis, type 1 (NF1)
• Neurofibromatosis-Noonan syndrome (NF1)
• Ollier disease/ Dyschondroplasia [panelapp] (IDH1)
• Paget disease of bone 2, early-onset (TNFRNF11A)
• Paget disease of bone 3 (SQSTM1)
• Paget disease of bone 5, juvenile-onset (TNFRSF11B)
• Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic (HRAS, NRAS)
• Watson syndrome (NF1)