ESPE Abstracts

Chromosomal microdeletions and microduplications have been associated with syndromic forms of intellectual disability (ID). The Xq28 duplication syndrome is an X-linked intellectual disability syndrome characterized by variable degrees of cognitive impairment (typically more severe in males), a wide spectrum of neurobehavioral abnormalities, and variable facial dysmorphic features. All males reported to date with the syndrome have a moderate-to-severe intellectual disability. This case report showed different clinical characteristics related to microarray abnormality involving a loss of ~111-kilobases (kb) within cytogenetic band Xq28 and a gain within cytogenetic band 20q11.22. We report a boy who presented at 7 years of age with special facial features, growth failure, and bilateral hydronephrosis (grade 3) due to posterior urethral valve which was previously operated on, sensorineural hearing loss (on hearing aids), speech delay. No other developmental or behavioral issue was reported by his parents. Measurements showed: Ht SDS = -5.3, BMI SDS = -0.02, mid parental HtSDS = -1. Investigations showed: FT4: 10.7 pmol/l (low), TSH: 2.75 mIU/l, IGF1: 7.0 mg /l (Low) (-4SD), Glucose: 3.3 mmol/l, Creatinine: 68 umol/l, Albumin Lvl: 43.3 gm/l, ALT: 13.6 U/l, Bicarbonate: 22 mmol/L. He had normal calcium homeostasis and electrolyte levels. Bone age was 3 years when the chronological age was 7 years. He was started on L thyroxine 50 mg OD. Growth hormone stimulation test revealed severe GH deficiency with peak GH = 2 mg/L. MRI of the pituitary showed pituitary hypoplasia. The patient was started on GH 0.05 mg/kg. Microarray study showed the following abnormality: arr[GRCh37] Xq28(147806444-147917562)x1, arr[GRCh37] 20q11.22(33458005-33557168)x3. The analysis revealed two copy number changes. A loss of ~111-kilobases (kb) within cytogenetic band Xq28. The loss causes intragenic deletion of the AFF2 gene. The second change is a gain of ~99-kilobases (kb) within cytogenetic band 20q11.22, the duplicated segment contains GSS, MYH7B, GGT7, and ACSS2 genes.

Discussion: Mutations in the AFF2 gene cause fragile XE syndrome, with mild intellectual and learning disabilities. The 20q11.2 microdeletion is characterized by intellectual disability (ID), developmental delay, and facial dysmorphism, but a gain within the cytogenetic band 20q11.22 was not described before.

Conclusion: This patient with this peculiar genetic constitution: arr[GRCh37] Xq28(147806444-147917562)x1, arr[GRCh37] 20q11.22(33458005-33557168)x3 presented with severe growth retardation, GH deficiency, central hypothyroidism, sensorineural hearing loss, and pituitary hypoplasia.