Clinical variability is
remarkable, with the spectrum of features ranging from only
minimally affected individuals to those with the full picture
of malformations and lethal outcome. Minimally affected
patients may show only downslanting palpebral fissures and
preauricular pits or tags. However, CES usually is characterized
by the combination of coloboma of the iris (unior bilateral),
total or partial coloboma of the choroidea and/or optic nerve,
microphthalmia (most often unilateral), downslanting palpebral
fissures, preauricular tags and/or pits, and anal atresia with
rectovesical, rectovaginal, or rectovulvar fistulas in females
and rectovesical, rectourethral, or rectoperineal fistulas in
males. Other frequently encountered anomalies include renal
anomalies (absence of one or both kidneys, supranumeric
kidneys, renal hypoplasia, hydronephrosis) and congenital
cardiovascular malformations (tetralogy of Fallot, total
anomalous pulmonary venous drainage, persistent left superior
vena cava, Eisenmenger complex) in more than one third of
patients. Additional craniofacial stigmata may include
aniridia, cataract, hypertelorism, strabismus, inner epicanthic
folds, flat nasal bridge, choanal atresia, cleft lip and
palate, mandibular hypoplasia, additional ear malformations
(reduction of the auricles to several tags only and atresia of
the external auditory canal), and hypothalamic growth hormone
deficiency (without severe growth retardation). Skeletal
anomalies may present as absence or synostosis of ribs,
scoliosis, vertebral fusions, and limb malformations (radial
aplasia, duplication of the hallux, absent toes and
sirenomelia). Visceral anomalies include pulmonary segmentation
defects, intestinal malrotation, biliary atresia, Hirschsprung
disease, Meckel diverticulum, umbilical hernia, uterus
hypoplasia and vaginal atresia in girls, and hypospadia in boys.
Cases of CES in combination with spina bifida or
myelomeningocele have been reported. Normal or only slightly
delayed mental development is common, but in rare cases,
patients with the full picture of the syndrome have severe
mental retardation.