title: Wide clinical variability in conditions with coarse facial features and hypertrichosis caused by mutations in ABCC9.
abstract: We present two previously unreported and unrelated female patients, one with the tentative diagnosis of acromegaloid facial appearance (AFA), the other with the tentative diagnosis of hypertrichosis with acromegaloid facial appearance (HAFF) with or without gingival hyperplasia. Main clinical features of HAFF were generalized hypertrichosis terminalis and coarse facial features. In both patients, pregnancy was complicated by polyhydramnios, and both had hyperbilirubinemia and persistent fetal circulation. Development was normal in one patient and slightly delayed in the other. At 13 years, both had round faces with full cheeks, thick scalp hair and eyebrows, a low frontal hairline, hirsutism, hyperextensible joints and deep palmar creases. One of them additionally showed gingival hypertrophy and epicanthus, the other one was macrocephalic at birth and at the age of 13 years and suffered from repeated swelling of the soft tissue. Array analysis excluded a 17q24.2-q24.3 microdeletion, which has been reported in patients with hypertrichosis terminalis with or without gingival hyperplasia. Sequencing of the mutational hotspots of the ABCC9 gene revealed two different de novo missense mutations in the two patients. Recently, identical mutations have been found recurrently in patients with Cantú syndrome. Therefore, we propose that ABCC9 mutations lead to a spectrum of phenotypes formerly known as Cantú syndrome, HAFF and AFA, which may not be clearly distinguishable by clinical criteria, and that all patients with clinical signs belonging to this spectrum should be revisited and offered ABCC9 mutation analysis.
authors: Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany. christina.czeschik@uni-due.de
authors: Johanna Christina
authors: JC
authors: Czeschik
authors: Claudia
authors: C
authors: Voigt
authors: Timm O
authors: TO
authors: Goecke
authors: Hermann-Josef
authors: HJ
authors: Lüdecke
authors: Nicholas
authors: N
authors: Wagner
authors: Alma
authors: A
authors: Kuechler
authors: Dagmar
authors: D
authors: Wieczorek
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000172:Acromegaly / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D006332:Cardiomegaly / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D006983:Hypertrichosis / Q000175:diagnosis* / Q000235:genetics; D017880:Limb Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000235:genetics; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors
chemical_list: C577510:ABCC9 protein, human; D018528:ATP-Binding Cassette Transporters; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors