Table 2.
Syndromes associated with incomplete müllerian fusion (IMF).
| Syndromes | Somatic Findings | Uterine anomaly | Etiology |
|---|---|---|---|
| Acro-renal mandibular | Limb deficiencies, diaphragmatic hernia, ectrodactyly of hand and foot, absence of radius and metacarpal V, kidney dysplasia | Uterus didelphys | Autosomal recessive |
| Apert | Apert Craniosynostosis and midface hypoplasias with syndactyly of hands and feet, cardiac and renal defects | Bicornuate uterus | Autosomal Dominant FGFR2 gene mutation |
| Bardet-Biedl | Mental retardation, Pigmentary retinopathy, polydactyly, obesity, hypogonadotropic hypogonadism | “Uterus duplex, vaginal septa” | Autosomal recessive BBS1-14 mutations |
| Beckwith-Wiedemann | Omphalocele, macroglossia, overgrowth, clitoral enlargement | IMF | Imprinting abnormality, hypo-, hypermethylation of 11p15.5 |
| Caudal duplication | Duplication of sacrum, lumbar vertebrae, anus, large bowel, external genitalia | Duplication of uterus and cervix | Unknown |
| Caudal regression | Agenesis of sacral and lumbar regions | Duplication of uterus and cervix | Unknown |
| Cloacal exstrophy | Common urogenital sinus and rectum, renal anomalies, vertebral defects | IMF | Unknown |
| de Lange | Growth retardation, microcephaly, mental retardation, synophrys, limb anomalies | IMF | Mutations in NIPBL, SMC1A, SMC3 |
| Donohue | Elfin facies, enlarged ears, low-set ears, prominent breasts, abnormal carbohydrate metabolism, insulin receptor defect | IMF | Autosomal Recessive Insulin Receptor gene mutations |
| Female pseudohermaphroditism with renal and gastrointestinal anomalies | Genital ambiguity, urologic and gastrointestinal anomalies, vertebral and radial anomalies, renal absence | Uterine Didelphys | Unknown |
| Fraser | Cryptophthalmos, nose and ear anomalies, laryngeal stenosis, renal agenesis, mental retardation | Bicornuate uterus | Autosomal recessive FRAS1, FREM2, GRIP1 mutations |
| Fryns | Coarse facies, cleft palate, pulmonary hypoplasias, diaphragmatic defects | Bicornuate uterus | Autosomal recessive No gene identified yet |
| Halal | Digital hypoplasias, upper limb shortening, ectrodactyly | Uterine didelphys with | Autosomal Dominant Unknown gene |
| Hydrolethalus | Hydrocephaly, neural tube defects, micrognathia, deep set eyes, cleft palate, malformed respiratory tract, cardiac anomalies, club feet, polydactyly | “Uterus duplex” | Autosomal recessive KIF7 and HYLS1 mutations |
| Jarcho-Levin | Spondylocostal dysostosis: hemivertabrae, vertebral absences and fusion, respiratory defects, cardiac defects, short neck and chest, hernias | Uterine didelphys | Autosomal recessive MESP2 mutations |
| Meckel | Encephalocele, postaxial polydactyly, dysplastic polycystic kidneys, male pseudohermaphroditism | Bicornuate uterus | Autosomal recessive MSK1, TMEM216, TMEM67, CEP290, RPGRIP1L, CC2D2A mutations |
| Popliteal Pterygium | Pterygium of popliteal, antecubital, and crural regions, cleft lip and palate, digital hypoplasia | IMF | Autosomal Dominant IRF6 mutations Autosomal Recessive RIPK4 |
| Roberts | Tetraphocomelia, craniofacial abnormalities, corneal clouding, cardiac and renal anomalies | Bicornuate uterus | Autosomal recessive ESCO2 mutations |
| Rüdiger | Mental retardation, coarse facies, bifid uvula, ureteral stenosis, thickened palms and soles, inguinal hernias, poor cartilaginous formation | Bicornuate uterus | Autosomal recessive Unknown gene |
| Thalidomide embryopathy | Tetraphocomelia, especially radius, tibia, femur, midline facial hemangioma, nerve palsies, and cardiac defects | Septate uterus and vagina | Teratogen |
| Urogenital adysplasia | Unilateral or bilateral renal agenesis, flattened facies, pulmonary hypoplasias, limb deformations | Unicornuate or Bicornuate uterus | Unknown: multifactorial, epigenetic inheritance |
Listed here are genetic syndromes that may be associated with incomplete Müllerian fusion (IMF). Other phenotypic characteristics of the genetic syndromes, modes of inheritance, and known genetic mutations are presented.