Endocrine Abstracts

JOINT1823

Background: Cat Eye Syndrome (CES), also known as Schmid-Fraccaro syndrome, is a rare chromosomal disorder typically caused by trisomy or partial tetrasomy of chromosome 22 (inv dup 22pter to 22q11. 1). It is characterized by a classic triad of iris coloboma, anal atresia, and ear anomalies, seen in about 40% of cases. The clinical spectrum often includes features such as hypertelorism, down-slanting palpebral fissures, preauricular pits, and intellectual disability. Chromosomal rearrangements in the 22q11. 2 region can affect midline structures, such as the pituitary gland, leading to growth hormone (GH) deficiency and other hypothalamic-pituitary axis abnormalities. Although this case was previously described by other authors at birth (Serra et al. 2022), our aim is to present the long-term follow-up and the therapeutic outcome.

Case Presentation: We present the case of a full-term newborn from healthy parents, following a normal pregnancy and birth. The infant developed persistent hypoglycemia and cholestatic jaundice shortly after birth. Physical examination revealed hypotonia, anorectal malformation with the anal outlet located in the vaginal fornix, along with facial dysmorphisms, including hypertelorism, microphthalmia, and dysplastic ears. Ophthalmologic evaluation confirmed bilateral iris coloboma, and echocardiogram revealed atrial septal defect. Endocrine testing showed congenital deficiencies of cortisol, GH, and thyroid hormones, leading to the diagnosis of hypopituitarism. Following this, hydrocortisone and levothyroxine were initiated. No symptoms suggestive of diabetes insipidus were observed. Brain MRI documented aplasia of the anterior pituitary gland, agenesis of the pituitary stalk, and ectopic neurohypophysis. Array CGH confirmed partial tetrasomy of chromosome 22 (22q11. 1q11. 21), establishing the diagnosis of CES. After the initial hospitalization at birth, the patient began multidisciplinary follow-up and was started on GH replacement therapy, along with oral hydrocortisone and levothyroxine, which allowed for adequate glycemic and thyroid control. At the current age of 3, despite early developmental delay and growth failure, she has shown significant catch-up growth (height: from -6 to -3. 6 SDS; weight: from -6 to -3. 3 SDS). Cholestasis has improved with cortisol therapy, although transaminases and gamma-GT have remained elevated.

Conclusion: Congenital hypopituitarism can be a part of the highly variable phenotypic spectrum of CES, often presenting with neonatal hypoglycemia, cholestasis, and severe growth delay. Six other cases with pituitary abnormalities and hormonal defects have been reported in the literature (four with isolated GH deficiency, two with hypogonadotropic hypogonadism). Cortisol deficiency is known to impair bile recirculation, but persistent hypertransaminasemia and elevated gamma-GT suggest a multifactorial cause of hepatic cytolysis despite hydrocortisone treatment.