Severe intrauterine (with oligohydramnios) and postnatal growth retardation
are almost always present. The disease may affect head and neck
(microcephaly, closed anterior fontanelle at birth, prominent occiput,
sloping forehead, low-set and dysplastic ears, large protruding eyes,
strabismus, big, prominent nose, mandibular hypoplasia, high vaulted narrow
palate, unilateral choanal atresia, short neck), the urogenital tract
(micropenis, cryptorchidism, obstructive hydronephrosis), the skeleton (hip
dislocation, joint flexion deformities, flexion contractures in the big
joints, short limbs, brachydactyly, clinodactyly of the fifth digit, delayed
bone age, abnormal vertebral size and shape [cervical clefts,
platyspondyly], flared iliac wings, shallow acetabula, delayed metaphyseal
maturation, bowed femurs and humeri) and the central nervous system (delayed
psychomotor development, seizures, micrencephaly, corpus callosum agenesis,
gyral anomalies, enlarged lateral ventricles, hypoplastic cerebellum and
frontal lobes, agenesis of the cerebellar vermis, heterotopias). Other
features include alopecia, dry skin, bilateral simian creases, and decreased
sweating. Tetralogy of Fallot and renal leakage have been described in one
case. This disease is generally lethal within the first year of life. The
oldest survivor died at 6.5 years of age. The recorded causes of death are most
often infections, such as meningitis, meconium peritonitis, aphthous
stomatitis, sepsis, and airway infections with pneumonia.