A 47,XX,+der(21)t(8;21)(q24.2;q21.1) karyotype in a patient with mild intellectual disability, cleft lip, hashimoto thyroiditis and hirsutism

Abstract

Here, we present a patient with an apparent trisomy 21 (Fig. 1) and a mild phenotype.The patient, a 22-year-old woman, came to our observation because of mild intellectual disability. She is the only child of healthy and unrelated parents; she was born at 32 weeks of gestation after an eventful pregnancy except for a threatened miscarriage during the first trimester of pregnancy; her mother was 21 and her father 25. Family history was unremarkable.Birth weight was 1,970 g (>50th centile corrected age), length 42 cm (50th centile corrected age) and head circumference 29 cm (50th centile corrected age).At birth she presented with respiratory distress and apneic crisis that did not require mechanical ventilation. She had a unilateral cleft lip, an angioma localized on the superior portion of the helix of the right ear, and a skeletal anomaly of the left thumb, which was surgically corrected. The parents did not keep any medical record of the surgical operation, thus it is not possible to be more specific about this anomaly. Psychomotor milestones have been reported as mildly delayed. During infancy, she showed distinctive morphological features of the face: high forehead, depressed nasal bridge with triangular and bulbous nasal tip, thin eyebrows, long philtrum with thin upper lip vermilion (Fig. 2). Axillary and pubic hair had been present since 3 years of age and FSH levels were high at this age (7 mUI/ml), whereas, LH levels were normal. Menarche occurred at 10 years old and menstruation cycles were regular. At the age of 19, excessive growth of thick dark hair appeared on her body, mainly on the face, the chest, and the upper back. Repeated evaluation of gonadotropins and gonadal steroids levels was normal. Only testosterone levels were slightly above the normal range: total testosterone was 0.9 ng/ml (normal range 0.1-0.8 ng/ml) and free testosterone was 4.71 pg/ml (normal range 0.3-3.2 pg/ml). Brain MRI was normal. Ultrasound examination of the pelvis detected a micropolycystic left ovary. She developed chronic autoimmune thyroiditis with normal thyroid function. Her height was 161 cm, weight 95 kg, and BMI was 36.6 kg/m 2 .Karyotype analysis revealed an apparent trisomy 21. Parental chromosome analysis detected a balanced translocation t(8;21) (q24.2;q21.