An inherited neurodevelopmental disorder with large
phenotypic variability, ranging from nearly normal to severe malformations
of many organs.
Schmid-Fraccaro Syndrome; Partial Tetrasomy of Chromosome
22; Coloboma-Anal Atresia Syndrome; Ocular Coloboma-Imperforate Anus
In 1879 the Swiss ophthalmologist O. Haab was the first to describe a syndrome of anal
atresia combined with coloboma. However, the extra chromosome 22 responsible
for the syndrome was detected by W. Schmid from Zurich, Switzerland, and M.
Fraccaro from Pavia, Italy, who named it cat eye syndrome (CES) because of
the inferior coloboma (resulting in a vertical, cat-like pupil) and the
downslanting palpebral fissures, although more than 50% of patients have
no signs of coloboma.
In Switzerland, the incidence has been estimated to be 1
in 50,000-150,000 live births. This most likely is representative of other
countries, as no racial predilection has been reported.
Autosomal dominant. Trisomy or tetrasomy 22
(22q11). The additional chromosome 22 generally arises de novo from one of
Clinical features (mainly coloboma, anal atresia, and
preauricular pits/tags) may lead to the diagnosis. However, because of the
wide clinical spectrum of this disorder, the final diagnosis is made by
fluorescent in situ hybridization (FISH), which shows the presence of an
extra marker chromosome derived from chromosome 22 (partial extra chromosome
or duplication) containing two copies of the CES region.
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. ...