Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome

Abstract

Background Cat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2). Case presentation We report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis. Conclusions CES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.

Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases

“…Brain malformations are reported in sporadic CES cases but are not usually associated with CES (Jedraszak et al, 2015; Karcaaltincaba et al, 2010; Melo et al, 2013; Serra et al, 2022). We noted some brain malformation observed at an unexpected frequency, with 24% of CES patients in our cohort presenting with such malformations.…”

A novel SALL1 C757T mutation in a Chinese family causes a rare disease --Townes-Brocks syndrome

“…Diagnosis of Townes-Brocks syndrome (TBS) involves a combination of clinical evaluation, imaging studies, and genetic testing to identify mutations in the SALL1 gene [7]. During the diagnostic process, it is crucial to exclude other rare syndromes, such as VACTERL/VATER syndrome, cat's eye syndrome, and Goldenhar syndrome, that have TBS overlapping signs [27][28][29]. Treatment is generally supportive and may involve surgical intervention for certain malformations or the use of hearing aids for hearing loss [6].…”

New insights on partial trisomy 3q syndrome: de novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception

“…An overall careful comparison of the clinical features described in other 3q duplications can help clarify the influence of specific genomic regions on the phenotype. Then, the phenotypic variability between the patients reported to date can be explained by variations of the number (and type) of active genes present in chromosomal fragments of different sizes, according to contiguous gene syndromes [ 3 , 21 – 27 ]. Indeed, the genes included in the present duplicated chromosome are around 80, and some of them are associated with well-known phenotypes of the 3q duplication syndrome [ 2 ].…”