Table 1.
Major clinical features of Cantú syndrome
| Cantú syndrome clinical manifestations | III.3 | II.8 | II.3 | III.1 | Molecularly proven Cantú syndrome n = 30 [1, 4, 5, 15, 16] |
|---|---|---|---|---|---|
| Cranio-facial dysmorphology | |||||
| Coarse facial appearance | + | + | + | + | 30/30 [1, 4, 5, 15, 16] |
| Broad nasal bridge | + | + | + | + | 24/26 [1, 5, 15] |
| Bulbous nose | + | + | + | + | 29/30 [1, 4, 5, 15, 16] |
| Small nose/anteverted nostrils | − | − | − | 11/13 [5, 15] | |
| Prominent mouth with thick lips | + | + | + | − | 29/30 [1, 4, 5, 15, 16] |
| Long philtrum | + | + | + | + | 28/29 [1, 4, 5, 15] |
| Macroglossia | + | + | + | + | 15/28 [1, 5, 15, 16] |
| Gingival hyperplasia | − | − | − | + | 10/18 [1, 4, 5, 16] |
| High or narrow palate | − | − | − | − | 9/12 [5, 16] |
| Anterior open bite | − | − | − | − | 3/11 [5] |
| Epicanthal folds | − | − | − | − | 19/27 [1, 5, 15] |
| Short neck | − | − | − | − | 5/11 [5] |
| Multiple labial frenula | − | − | − | − | One single case [16] |
| Hair | |||||
| Congenital generalized hypertrichosis | + | + | + | + | 30/30 [1, 4, 5, 15, 16] |
| Abundant/curly eyelashes | − | − | − | − | 9/11 [5] |
| Spiky hair | − | − | − | − | 2/14 [1] |
| Cardiovascular | |||||
| Cardiomegaly | − | − | + | − | 15/30 [1, 5, 15, 16] |
| Concentric hypertrophy of the ventricles | − | − | − | − | 13/30 [1, 4, 5, 15, 16] |
| Pericardial effusion | − | + | − | − | 4/29 [1, 4, 5, 15] |
| Pulmonary hypertension | n.a. | n.a. | n.a. | n.a. | 4/29 [1, 4, 5, 15] |
| Patent ductus arteriosus | n.a. | n.a. | n.a. | n.a. | 11/16 [1, 4] |
| Patent foramen ovale | n.a. | n.a. | n.a. | n.a. | 2/16 [1, 15] |
| Atrial septal defects | − | − | − | − | 2/14 [1] |
| AV block or fascicular block | − | − | − | − | 1/2 [15] |
| Thoracic aorta aneurism | n.a. | n.a. | n.a. | n.a. | One single case [15] |
| Myocarditis | − | − | − | + | |
| Skeletal abnormalities | |||||
| Thickened calvarium | − | − | + | − | 9/30 [1, 4, 5, 15, 16] |
| Craniosynostosis | − | − | − | − | 1/2 [15] |
| Broad ribs | − | − | − | − | 16/30 [1, 4, 5, 15, 16] |
| Narrow thorax | − | − | − | − | 4/11 [5] |
| Platyspondyly and ovoid vertebral bodies | n.a. | n.a. | n.a. | n.a. | 5/26 [1, 5, 16] |
| Narrow obturator foramen | n.a. | n.a. | n.a. | n.a. | 2/11 [5] |
| Coxa vara/valga | − | − | − | − | 3/11 [5] |
| Scoliosis | − | − | − | − | 6/27 [1, 4, 5] |
| Osteopenia | n.a. | n.a. | n.a. | n.a. | 2/12 [5, 16] |
| Delayed bone age | − | n.a. | n.a. | n.a. | 3/12 [5, 16] |
| Hypoplastic bones | − | − | − | − | 2/26 [1, 5, 16] |
| Erlenmeyer flask-like long bones with metaphyseal flaring | n.a. | n.a. | n.a. | n.a. | 6/26 [1, 5, 16] |
| Hyperextensibility of joints | − | − | − | − | 15/27 [1, 4, 5] |
| Enlarged medullary canal | n.a. | n.a. | n.a. | n.a. | 8/12 [5, 16] |
| Pectus carinatum | − | − | − | − | 2/11 [5] |
| Skin | |||||
| Loose, soft and/or wrinkled skin | − | − | − | − | 18/27 [1, 5, 15] |
| Deep palmar and plantar creases | − | − | − | − | 14/27 [1, 5, 15] |
| Persistent fingertip pads | − | − | − | − | 12/26 [1, 5, 16] |
| Keloid formation | − | − | − | − | One single case [16] |
| Endocrine system | |||||
| Enlarged pituitary sella turcica | − | − | − | − | One single case [5] |
| Pituitary hyperplasia | − | − | − | − | One case with CS phenotype, not proven molecularly [11] |
| GH deficiency | − | − | − | − | One single case associated to KCNJ8 gene mutation [8] |
| Pituitary adenoma | + | − | + | − | No reported cases |
| Other manifestations | |||||
| Macrosomia at birth (adult height usually normal) | − | − | − | − | 19/29 [1, 4, 5, 15] |
| Polyhydramnios | n.a. | n.a. | n.a. | n.a. | 12/29 [1, 4, 5, 15] |
| Developmental and/or speech delay | − | − | − | − | 10/29 [1, 4, 5, 15] |
| Edema/ lymphedema | − | − | − | − | 5/11 [5] |
| Pyloric stenosis | − | − | − | − | 1/11 [5] |
| Feeding problems and poor intestinal motility | − | − | − | − | 8/14 [1] |
| Hepatomegaly/ splenomegaly | − | − | − | − | 2/14 [1] |
| Immune dysfunction and recurrent infections | − | − | − | − | 11/27 [1, 5, 15] |
| Tracheo/broncho/laryngomalacia | n.a. | n.a. | n.a. | n.a. | 3/14 [1] |
| Hoarse voice | − | − | − | − | 3/14 [1] |
| Large hands | − | − | + | − | 2/3 [15, 16] |
| Umbilical hernia | − | − | − | − | 5/12 [5, 15] |
| Renal abnormalities | − | − | − | − | 1/11 [5] |
| Genital abnormalities | − | − | + (small uterus) | − | 3/12 [5, 16] |
| Neurological manifestations | |||||
| Migraines | − | − | − | − | 5/10 [12] |
| Seizures | − | − | − | − | 2/10 [12] |
| Hypotonia | − | − | − | − | 3/10 [12] |
| Autism | − | − | − | − | 1/10 [12] |
| Attention difficulties and behavioral problems | − | − | − | − | 4/10 [12] |
| Cerebral atrophy | − | − | − | − | 2/10 [12] |
| White matter changes | + | − | − | − | 3/10 [12] |
| Tortuous cerebral vasculature | − | − | − | − | 5/10 [12] |
| Tortuous retinal vessels | n.a. | n.a. | n.a. | n.a. | 2/10 [12] |
Features present in the reported alive family members are marked with (+); absent features are marked with (−); features that are unknown or were not actively investigated are marked with (n.a.). The right column shows the presence of manifestations in patients with mutation positive Cantú syndrome reported in the literature