The malformations associated with cat eye syndrome span a broad clinical spectrum [1] [2]. Commonly occurring malformations include preauricular anomalies, anal atresia, and coloboma of the iris. The following malformations are associated with CES [2] [3] [4]:

• Eye: A majority of patients with CES present with coloboma of the iris, choroid, and/or the retina; coloboma may occur unilaterally or bilaterally. The iris may have a "keyhole" appearance due to the absence of iris tissue (aniridia). Other, less common, features include clouding of the cornea, microphthalmia, cataract, and/or Duane syndrome [3].
• Ears: Phenotypic abnormalities of the ears consist of small outgrowths of skin or preauricular tags and/or pits, low-set or small ear size, and/or atresia or absent external ear canals [2].
• Head/neck: Craniofacial malformations such as mandibular hypoplasia, cleft lip, down-slanting palpebral fissures, hypertelorism, inner epicanthic folds, and/or flat nasal bridge may be present [5].
• Gastrointestinal (GI): GI malformations include an umbilical hernia, intestinal malrotation, biliary atresia, and/or Hirschsprung disease.
• Genitourinary (GU): A significant number of patients with CES present with anal atresia. Less commonly, patient's may have an anorectal fistula into the vagina (in females), bladder, urethra, or perineum [3]. Males with CES may have undescended testes or hypospadias [6].
• Cardiac: Congenital heart defects associated with CAE include total anomalous pulmonary venous return or tetralogy of Fallot [7].
• Renal: Kidney malformations consist of renal atresia, hydronephrosis, supernumerary kidneys, and/or renal hypoplasia of one or both kidneys.
• Musculoskeletal: Spinal defects and limb malformations (e.g., radial aplasia, duplication of the hallux, absent toes and sirenomelia), absence or synostosis of ribs, scoliosis, and/or vertebral fusions have been observed in patients with CES [3].
• Cognitive: No cognitive impairment to moderate intellectual disability have been reported; most individuals with CES have a mild degree of intellectual impairment.

• Fishing

  FISH studies demonstrated that the marker is a derivative of chromosome 22 and enabled us to provide the family with additional prognostic information. [ncbi.nlm.nih.gov]

  Fluorescence in situ hybridization (FISH) with specific probes is needed to detect a low level mosaicism. [orpha.net]

• Antimongoloid Slant

  Additionally, the patient had antimongoloid slant of the eyes, epicanthal folds, preauricular sinuses, cardiac malformations, skeletal malformations, and mental retardation suggestive of the cat-eye syndrome. [ncbi.nlm.nih.gov]

• Torticollis

  Here, we present a 9-month-old female who at birth was noted to have multiple defects, including facial asymmetry with asymmetric retrognathia, bilateral mandibular hypoplasia, branchial cleft sinus, right-sided muscular torticollis, esotropia, and an [ncbi.nlm.nih.gov]

• Genu Valgum

  Clinically the patient shows: moderate psychic retardation, high forehead, epicanthus, strabismus, microretrognathism, large, low inserted ears, kypho-scoliosis, genu valgum; mild hypothyroidism. [ncbi.nlm.nih.gov]

• Widely Spaced Nipples

  On examination, she had microcephaly, periorbital puffiness, a long philtrum, a broad nasal bridge and retrognathia, up slanting palpebral fissures, widely spaced nipples, a sacral dimple and right upper limb postaxial polydactyly. [ncbi.nlm.nih.gov]

• Fissure of the Nipple

  On examination, she had microcephaly, periorbital puffiness, a long philtrum, a broad nasal bridge and retrognathia, up slanting palpebral fissures, widely spaced nipples, a sacral dimple and right upper limb postaxial polydactyly. [ncbi.nlm.nih.gov]

• Broad Nasal Bridge

  On examination, she had microcephaly, periorbital puffiness, a long philtrum, a broad nasal bridge and retrognathia, up slanting palpebral fissures, widely spaced nipples, a sacral dimple and right upper limb postaxial polydactyly. [ncbi.nlm.nih.gov]

• Neck Mass

  We present the clinical and molecular findings of a 9-month-old girl with features of CES and also a palpable midline neck mass proved to be an extragonadal mature teratoma, additionally characterized by array comparative genomic hybridization (aCGH). [ncbi.nlm.nih.gov]

• High Forehead

  Clinically the patient shows: moderate psychic retardation, high forehead, epicanthus, strabismus, microretrognathism, large, low inserted ears, kypho-scoliosis, genu valgum; mild hypothyroidism. [ncbi.nlm.nih.gov]

• Primary Amenorrhea

  Although Müllerian agenesis is the second most common cause of primary amenorrhea the underlying etiology in most cases is unknown. [ncbi.nlm.nih.gov]

Cat eye syndrome is diagnosed using multimodal testing. Detection of a fetal abnormality on a routine prenatal ultrasound is often the first indication for a need of additional workup. Amniocentesis, chorionic villus sampling, or blood-based genetic testing (non-invasive prenatal testing) are used to perform a fetal chromosomal analysis prenatally. Tetrasomy of chromosome 22 is highly suggestive of cat eye syndrome [8] [9]. The extent of malformations and the organs affected in utero are determined using ultrasound.

Cat eye syndrome can be detected after birth by physical examination, clinical evaluations, and chromosomal analysis. The physical exam should consist of screening for phenotypic features of cat eye syndrome such as coloboma and periauricular abnormalities. Clinical evaluation is performed using computed tomography of the chest and abdomen to identify malformations of internal organs and organ-based testing (e.g., echocardiography, ultrasound, neuro- or musculoskeletal MRI, eye exam, hearing test).

Molecular tests including whole chromosome paint, chromosomal analysis, FISH, array genomic hybridization and/or the Multiplex Ligation-dependent Probe Amplification assay are used to confirm the diagnosis of cat eye syndrome [8] [10] [11].

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   Jenson, Hal B et al., eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, PA: W.B. Saunders Company; 2000:1385-89, p. 1399-1400.
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