Abstract
Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP‐sensitive potassium (KATP) channels, respectively. It is characterized by congenital hypertrichosis, osteochondrodysplasia, extensive cardiovascular abnormalities and distinctive facial anomalies including a broad nasal bridge, long philtrum, epicanthal folds, and prominent lips. Many genetic syndromes, such as CS, involve facial anomalies that serve as a significant clue in the initial identification of the respective disorder before clinical or molecular diagnosis are undertaken. However, an overwhelming number of CS patients receive misdiagnoses based on an evaluation of coarse facial features. By analyzing three‐dimensional images of CS faces, we quantified facial dysmorphology in a cohort of both male and female CS patients with confirmed ABCC9 variants. Morphometric analysis of different regions of the face revealed gender‐specific significant differences in face shape. Moreover, we show that 3D facial photographs can distinguish between CS and other genetic disorders with specific facial dysmorphologies that have been mistaken for CS‐associated anomalies in the past, hence assisting in an earlier clinical and molecular diagnosis. This optimizes genetic counseling and reduces stress for patients and parents by avoiding unnecessary misdiagnosis.
Highlights
Cantú syndrome (CS; OMIM #239850) is a rare autosomal dominant condition characterized by a wide constellation of clinical features, namely coarse facial features, congenital hypertrichosis, osteochondrodysplasia and extensive cardiovascular anomalies including cardiomegaly, patent ductus arteriosus (PDA), pericardial effusion and dilated and torturous cerebral blood vessels
We present 3D imaging analysis in 20 CS patients
In order to compensate for the wide age range (2–22 years) and the changes in morphometric analysis according to age, we investigated differences in facial features in the following ageand gender-specific CS subgroups compared to respectively matched controls: Male subgroup 1, male subgroup 2, female subgroup 3 and female subgroup 4
Summary
Cantú syndrome (CS; OMIM #239850) is a rare autosomal dominant condition characterized by a wide constellation of clinical features, namely coarse facial features, congenital hypertrichosis, osteochondrodysplasia and extensive cardiovascular anomalies including cardiomegaly, patent ductus arteriosus (PDA), pericardial effusion and dilated and torturous cerebral blood vessels (Grange et al, 2019; Peter Hammond and Mieke M. van Haelst contributed Grange, Lorch, Cole, & Singh, 2006; Leon Guerrero et al, 2016; Scurr et al, 2011). Cantú syndrome (CS; OMIM #239850) is a rare autosomal dominant condition characterized by a wide constellation of clinical features, namely coarse facial features, congenital hypertrichosis, osteochondrodysplasia and extensive cardiovascular anomalies including cardiomegaly, patent ductus arteriosus (PDA), pericardial effusion and dilated and torturous cerebral blood vessels CS is caused by gain-of-function (GoF) pathogenic variants in ABCC9 and, less commonly, in KCNJ8, which encode the regulatory (SUR2) and pore-forming (Kir6.1) subunits, respectively, of ATP-sensitive potassium (KATP) channels(Brownstein et al, 2013; Cooper et al, 2014; Harakalova et al, 2012; McClenaghan et al, 2017; van Bon et al, 2012). There is considerable variation in the phenotypic spectrum, even within family members sharing the same ABCC9 variant (Roessler, Volker-Touw, Terhal, van Haaften, & van Haelst, 2018).
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