PMC6369518_01
Karyotype and SNP array. A) Karyotype showed 2 extra X chromosomes (red arrows). B) X chromosomes on SNP array shows 2 extra lines on B allele frequency plot (red arrows) compared to control showing heterozygous SNPs are separated into 3 distinct lines. The corresponding log R ratio plot shows a thicker line with higher log R ratio (black arrow) than control because extra chromosomes are calculated as duplication.
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F1
At 14 months of age, her facial dysmorphism, poor growth and developmental delay prompted additional evaluation including a karyotype that revealed tetrasomy X (Figure 1A). A SNP array was also performed to evaluate the characteristics of the extra X chromosomes (Figure 1B).
Bone age and MRI images of Rathke's cleft cyst. A) Bone age x-ray at chronological age of 17 months. A T1 sagittal scan is represented showing a non-enhancing 8 x 4 x 14 mm cystic lesion in the pituitary gland (yellow arrow). B) 17 months old. C) 7 years 10 months.
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F2
Her laboratory evaluation was remarkable for a low IGF-1 of 37ng/mL (reference range 49-342 ng/mL) and her bone age was delayed (1 month at chronological age of 17 months (Figure 2A). She also underwent a brain and pituitary MRI which showed delayed demyelination and an 8 x 4 x 13 mm cystic lesion in the sella turcica, indicating a Rathke's cleft cyst (Figure 2B). Serial MRIs performed over the years showed no change in the size of the cyst (Figure 2C).
Growth charts of patient. A) Infantile growth chart (0-2 years). B) Childhood growth chart (2-20 years).
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F3
Therefore, under clinical suspicion, she was diagnosed with growth hormone deficiency and at 21 months of age she started treatment requiring a low dose of growth hormone (0.13 mg/kg/week), to which she responded with improvement in IGF-1 and growth velocity, as is typical in this management of growth hormone deficiency (Figure 3A). A physiologic dose of hydrocortisone and of levothyroxine replacement were initiated and her growth improved accordingly (Figure 3B). At age 8, she was prescribed aripiprazole for behavioral outbursts and subsequently had significant weight gain, her BMI percentile increasing from 50th to 85th.
PMC6369518_02
Patient features. Pictures were taken at 15 months (A) and 12 years 8 months (B). Dysmorphic features including hyper-telorism, epicanthal folds and a flat nasal bridge are shown.
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F4
The patient's photograph is shown in Figure 4.