There is a wide variability in the expression of
the features of the syndrome. Involvement of the head and neck can present
as thickened calvarium, small sinuses paranasales, flat occiput, delayed
suture closure with large anterior fontanelle, prominent supraorbital ridges
with bushy brows, downwardly slanted palpebral fissures, hypertelorism,
blepharoptosis, large and prominent ears, large nose with broad base and
elongated philtrum, mandibular prognathism, maxillary/midfacial hypoplasia,
large mouth with big lips, and longitudinally furrowed tongue with a dorsal
groove. The facial features are generally not present at birth, but become
apparent by the second year of life, after which they become more
pronounced. Dental anomalies are numerous and may include congenital absence
of some teeth, delayed eruption, enamel hypoplasia, caries, early loss of
teeth, abnormal size and shape, malposition, malalignments, and periodontal
disease. Involvement of the musculoskeletal system presents as short thorax,
bifid sternum, pectus excavatum or carinatum, vertebral dysplasia, kyphosis,
scoliosis, delayed bone age, ligamental calcifications, hyperextensible
joints, muscle atrophy, large and soft hands with simian crease, and
tapering of the fingers. Cardiovascular involvement is frequent, with
features including atrial septal defects, persistent ductus arteriosus,
valvular anomalies (mitral valve prolapse, mitral regurgitation, tricuspid
insufficiency), impaired cardiac function, right ventricular hypertrophy,
restrictive cardiomyopathy, endomyocardial fibroelastosis, and ventricular
arrhythmias. Central nervous system features consist of generalized
hypotonia, which may be the earliest presenting sign and related to
paroxysmal drop attacks (cataplexy or hyperexplexia). In addition, seizures,
hydrocephalus, agenesis of the corpus callosum, abnormal gyration, faulty
cortical lamination, calcification of the falx cerebri, sensorineural
hearing loss, mental retardation, a tendency to obsessive-compulsive
behavior, and cervical radiculopathy (secondary to calcification of the
ligamentum flavum and consequent stenosis of the spinal canal) have been
described. Inguinal and umbilical hernias and rectal and uterine prolapse
appear to be common in these patients. Liver cirrhosis, recurrent
respiratory infections, and emphysema have been described. Most of the
clinical findings become more pronounced with increasing age.