A congenital disorder presenting with neonatal macrosomia, macrocephaly, cardiac anomalies, osteochondrodysplasia, and congenital hypertrichosis.
Cantú-Garcia–Cruz-Sanchez–Corona-Hernandez-Nazará Syndrome; Cranio-Facio-Cardio-Skeletal Syndrome; Cranio-Facio-Fronto-Digital Syndrome; Hypertrichotic Osteochondrodysplasia.
Almost 70 cases have been reported in the literature to date.
First described in 1982 by the Mexican geneticist José Maria Cantú and colleagues in four patients (two of them siblings).
A significant number of cases appear to be sporadic. Originally, inheritance was considered to be autosomal recessive, but recent research seems to confirm autosomal dominant transmission. The defect is most often caused by dominant missense mutations in the ABCC9 gene (ATP-Binding Cassette, Subfamily C, Member 9, also known as SUR2) on chromosome 12p12.1. Cantú Syndrome is now considered a potassium channelopathy, because ABCC9 encodes four regulatory subunits of pore-forming, transmembranous ATP-sensitive potassium channels in skeletal, smooth and cardiac muscle cells, and hair follicles. ABCC9 mutations seem to result in gene gain-of-function, thereby reducing the sensitivity of ATP-mediated potassium channel activation to the ADP/ATP ratio. Instead, Cantú Syndrome may also be caused by mutations in the KCNJ8 gene (Inwardly Rectifying Potassium Channel, Subfamily J, Member 8; also known as Kir6.1) and (similar to ABCC9) located on chromosome 12p12.1 and encoding for pore-forming subunits of the ATP-sensitive potassium channel. In a few affected patients, none of these mutations could be detected.
Based on the clinical findings of mild mental deficiency and the distinct malformations. Storage disorders (eg, glycogen storage diseases) must be excluded. Phenotypic variability exists among patients, even among family members sharing the same ABCC9 or KCNJ8 mutation. No sexual predilection has been reported.
More than 80% of the patients with Cantú Syndrome are macrosomic and oedematous at birth (birth weight and length frequently >90th percentile). Later in childhood, they often have little subcutaneous fat tissue, which leads to a muscular appearance, but this often changes due to weight gain after puberty. The disorder is characterized by coarse (acromegaloid) facial appearance with craniofacial anomalies such as macrocephaly (in >60%) with frontal bossing, low-set ears, exophthalmos, hypertelorism, epicanthal folds (in 83%), curly and/or abundant eyelashes, broad and flat nasal bridge (in 72%), small nose with anteverted nostrils (in over 90%), prominent mouth with long philtrum and thick lips (in up to 94%), high-arched palate (in 60%), macroglossia (in 60%), and gingival hyperplasia (in 70%). Musculoskeletal features may include hypotonia, osteochondrodysplasia with short stature and neck (although patients with a height well above average have also been described), enlarged sella turcica and vertical skull base (in 10%), thickened calvaria (in 50%), platyspondyly (in 76%), ovoid vertebrae (in 35%), wide ribs (in 70%), narrow chest (in 66%), bilateral coxa valga (in 20%), hypoplastic pelvis ...