Progressive onset of the disease is usual and
characteristic facies is observed later in infancy. Other clinical features
include short stature (94%), microcephaly (84%) with micrognathia
(100%), and various defects: cranial (frontal bossing, large fontanel, narrow
mouth and palate, choanal atresia), ear (low-set ears, hearing loss), eyes (heavy
eyebrows, long eyelashes, ptosis, glaucoma, coloboma, cataract epicanthal
folds), heart (33%) (patent ductus arteriosus, atrial or ventricular defect),
genitourinary (cryptorchism, hypospadias and renal defect), skin (keloid scars, hemangioma,
café-au-lait spots, hirsutism, nevus flammeus), neurological (corpus
callosum agenesis, hypotonia, hyperreflexia, seizures), and orthopedic (scoliosis,
spina occulta, pes planus, patellar dislocation, clinodactyly, syndactyly).
Swallowing troubles and feeding difficulties are frequent, as are
respiratory infection and asthma. There is an increased risk of tumor,
mainly of neurological origin (neuroblastoma, meningioma).