Skeletal, facial, and genital anomalies with possible cervical hypermotility and odontoid subluxation.
Aarskog-Scott Syndrome; Faciogenital Dysplasia; Faciodigitogenital Syndrome.
First described in 1970 by the Norwegian pediatric endocrinologist Dagfinn Aarskog.
Approximately 200 cases have been reported till date and birth prevalence has been estimated to be approximately 4 in 1,000,000.
Most commonly X-linked recessive transmission; however, genetic heterogeneity, autosomal dominant inheritance, and de novo mutations have been described. The mutation affects the faciogenital dysplasia 1 (FGD1) gene mapped to the Xp11.21 region.
The FGD1 gene encodes a guanine nucleotide exchange factor that specifically activates a particular set of guanosine triphosphatase involved in cellular signaling, migration, growth, and differentiation. Mutations in the FGD1 gene predominantly affect specific skeletal structures, including the face, cervical vertebrae, and distal extremities.
Primarily based on clinical features that are already recognizable at birth, although late diagnosis is not uncommon. Radiologic findings include cervical spine abnormalities, facial abnormalities, phalangeal defects, and delayed bone.
Patients present with anomalies of the face, genitalia, and limbs. Growth retardation usually becomes evident at age 2 to 4 years. The FGD1 mutation results in a wide range of skeletal anomalies including the craniofacial bones (round face with hypertelorism, flat midface due to maxillary and mandibular hypoplasia), abnormally shaped teeth with dysplastic enamel, the vertebrae (odontoid hypoplasia with hypermobility or subluxation, fused cervical vertebrae, spina bifida occulta), the ribs (extra pairs of ribs), the long bones, and phalanges (disproportionate acromelic dwarfism, hypoplastic phalanges). Pectus excavatum, ligamentous laxity of the hands, knees, and feet, or broad flat feet with lymphedema have been described. Limb anomalies consist of short thumbs, digital contractures, syndactyly, clinodactyly, brachydactyly, camptodactyly, interdigital webbing, and simian creases. Mild developmental delay and/or attention deficit hyperactivity disorder (ADHD) may be present, although IQ most often lies within the normal range. Ocular features may include ophthalmoplegia, large corneae, hyperopic astigmatism, downslanting of the palpebral fissures, strabismus, and ptosis. The nose has a broad bridge and is short and stubby with anteverted nostrils. The philtrum is long and wide with a broad upper lip. Cleft lip palate and a linear dimple below the lower lip have been reported. The ears may be low-set, cup shaped, and floppy. Associated heart defects have been described (eg, pulmonary stenosis, ventricular septal defect, aortic root dilation, coarctation, subvalvular aortic stenosis). Abnormal genital findings include cryptorchidism, scrotal folds encircling the penis ventrally (shawl scrotum). Other findings may include widow’s peak (V-shaped border of the frontal hair-line pointing to the center of the forehead), interstitial pulmonary disease, liver cirrhosis with portal hypertension, umbilical anomalies (hernia and/or protruding umbilicus with radiating cicatrix), inguinal hernias, imperforated ...