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Table 1 Characteristics of HGF (non-syndromic) and its co-existence with rare genetic diseases and syndromes

From: Gingival fibromatosis: clinical, molecular and therapeutic issues

Disease/syndrome Synonyms Prevalence Inheritance Chromosomal region/gene locus Causing or candidate gene Age of onset Clinical hallmarks
Hereditary gingival fibromatosis, HGF, ORPHA 2024, MIM 135300 [4] Autosomal dominant gingival fibromatosis, Autosomal dominant gingival hyperplasia, Hereditary gingival hyperplasia unknown GINGF All ages Slowly progressive hyperplasia of the maxillary and mandibular gingiva. Occurs with eruption of the permanent teeth, more rarely with the primary dentition or at birth [97100, 102, 163, 164].
Autosomal dominant 2p21-p22 [97] SOS1* [100]
Autosomal dominant 5q13-q22 CAMK4* [98]
Autosomal dominant 2p23.3-p22.3 [102] unknown
Autosomal dominant 11p15 [77] unknown
Gingival fibromatosis with craniofacial dysmorphism, ORPHA 2025, MIM 228560 [5] - <1/1 000 000 Autosomal recessive unknown unknown Neonatal Gingival fibromatosis, macrocephaly, bushy eyebrows with synophrys, hypertelorism, downslanting palpebral fissures, flattened nasal bridge, hypoplastic nares, cupid bow mouth, high arched palate [165167].
Gingival fibromatosis with progressive deafness, ORPHA 2027, MIM 135550 [6] Jones syndrome <1/1 000 000 Autosomal dominant unknown unknown Adults Gingival fibromatosis, progressive sensorineural hearing loss [168, 169].
Gingival fibromatosis/hypertrichosis syndrome, HTC3, ORPHA 2026, MIM 135400 [13] Congenital generalized hypertrichosis terminalis (CGHT), Hirsutism/congenital gingival hyperplasia syndrome, Hypertrichose avec ou sans hyperplasie gingivale, Hypertrichosis with or without gingival hyperplasia unknown Autosomal dominant, autosomal recessive 17q24.2-q24.3 [170] ABCA5* [171] Infancy, neonatal Generalized gingival fibromatosis occurring at birth or during childhood, hirsutism, generalized hypertrichosis predominantly affecting the face, upper limbs and midback [170175].
Ramon syndrome, ORPHA 3019, MIM 266270 [14] Cherubism/gingival fibromatosis/intellectual disability unknown Autosomal recessive unknown unknown Infancy Gingival fibromatosis, cherubism (fibrous dysplasia of the maxilla and mandible), delayed tooth eruption, narrow palate, short stature, kyphosis, scoliosis, mental deficiency, hypertrichosis, epilepsy [176178].
Zimmermann -Laband syndrome [9] Gingival fibromatosis/hepatosplenomegaly/other anomalies, Laband syndrome <1/1 000 000 Autosomal dominant 1q32.2, 3p, 8q: t(3;8)(p21.2;q24.3) [179] 3p14.3: t(3;17)(p14.3;q24.3) [180] KCNH1* [181, 182] Infancy, neonatal Gingival fibromatosis, delayed tooth eruption, prominent mandible, high arched palate, broad nasal bridge, thick lips, thick eyebrows, synophrys, myopia, cataracts, cardiomyopathy, hepatomegaly, splenomegaly, scoliosis, hyperextensible fingers, hypoplastic distal phalanges, mental disability, seizures [179184].
Infantile systemic hyalinosis (ISH), ORPHA 2176, MIM 236490 [7] Murray-Puretic-Drescher syndrome, Puretic syndrome <1/1 000 000 Autosomal recessive 4q21.21 [185, 186] ANTXR2* [187, 188] Childhood Gingival fibromatosis, osteolysis, osteoporosis, osteopenia, recurring subcutaneous tumors, recurrent infections, joint contractures, diarrhea [185191].
Juvenile hyaline fibromatosis (JHF), ORPHA 2028, MIM 228600 [8] - Antenatal, neonatal, infancy
Oculodental syndrome, Rutherfurd type, ORPHA 2709, MIM 180900 [12] Gingival hypertrophy/ Corneal dystrophy, corneal dystrophy with gum hypertrophy, Rutherfurd syndrome <1/1 000 000 Autosomal dominant unknown unknown Infancy, neoneatal Gingival fibromatosis, delayed primary teeth eruption, failure of secondary teeth eruption, corneal dystrophy, aggressive behaviour [192194].
Amelogenesis imperfecta/nephrocalcinosis syndrome, ORPHA 1031, MIM 204690** [10] Enamel - renal syndrome (ERS), Enamel - renal - gingival syndrome <1/1 000 000 Autosomal recessive 17q24.2 [154, 195, 196]. FAM20A* [154, 195197] Orodental phenotype – childhood; renal phenotype - adults Orodental phenotype: gingival fibromatosis, delayed tooth eruption, thin hypoplastic or absent enamel, microdontia and spaced teeth, intra-pulpal calcifications, root dilacerations of impacted teeth [154, 195, 196, 198]. Renal phenotype: bilateral medullary nephrocalcinosis, focal clusters of sclerosed glomeruli, marked periglomerular fibrosis with lymphocytic and plasma cell infiltration of the renal interstitium [199202].
Amelogenesis imperfecta/ gingival fibromatosis syndrome (AIGFS), ORPHA 171836, MIM 614253** [11]
  1. MIM, Mendelian Inheritance in Man; *SOS-1, Son-of-Sevenless-1; *CAMK, calcium/calmodulin-dependent protein kinase IV; *ABCA5, ATP-binding cassette, subfamily A, member 5; *KCNH1, potassium channel, voltage-gated, subfamily H, member-1; *ANTXR2, anthrax toxin receptor 2; *FAM20A, family with sequence similarity 20, member A.
  2. **Considering the significant overlap in the oral phenotype between cases with amelogenesis imperfecta (AI) with hamartomas and unerupted teeth, amelogenesis imperfecta/gingival fibromatosis syndrome (AIGFS), and enamel-renal syndrome (ERS) in the published literature as well as the pathognomonic character of the oral phenotype in the absence of other developmental health problems, the two OMIM entries for ERS and AIGFS (ERS:MIM#204690 and AIGFS:MIM#614253) have been combined [198]