Objective To assess the experience on prenatal diagnosis of Miller–Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome. Methods This was a retrospective study. Fetal MDS was diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA results, and pregnancy outcomes. Results Four cases were diagnosis as MDS by CMA. The most common sonographic features were ventriculomegaly (3/4) and polyhydramnios (2/4). Deletion sizes ranged from 1.5 to 5.4 Mb. All microdeletions were located at the MDS critical region and showed haploinsufficiency of the YWHAE, CRK, and PAFAH1B1. All patients chose to terminate the pregnancy. Parental chromosome analysis were preformed in three cases and demonstrated that two cases were de novo and one case was caused by inherited derivative chromosomes from parental balanced translocations. Conclusion The most common prenatal ultrasound findings of MDS were ventriculomegaly and polyhydramnios. CMA can improve diagnostic precision for detecting MDS.

The patient was hospitalized due to infertility, She was 30years-old, with a stature of 152 cm. Her intelligence quotient (IQ) was below average, and she had not experienced menarche so far. Through transvaginal ultrasonography, her uterus was visualized 3.8×3.5×2.5 cm 3 , and bilateral ovaries (left: 1.7×1.4 cm 2 and right: 1.6×1.1 cm 2 ). These results showed that the dimensions of two ovaries were under normal size. The sex hormone levels were detected via peripheral blood, with results of follicle stimulating hormone (FSH) 35.68 mIU/ml (normal range: 1.79-22.51), luteinizing hormone (LH) 15.78 mIU/ml (normal range:1.2-12.86), progesterone (P) 0.28 ng/ml (normal range:0.31-18.56), Luteinizing hormone releasing hormone (LHRH) stimulation testing showed abnormal gonadotropic hormones, and the levels of FSH and LH levels were high at different time points of baseline (0.5, 1, 2, and 3-hour post-stimulation) (Table 1). Serum insulin (12.65 IU/mL) levels were within normal range. In addition, her total thyroxine (TT4: 79.76 nmol/L) and total triiodothyronine (TT3: 1.34 ng/mL) were normal, while thyroid-stimulating hormone (TSH: 11.41 uIU/mL) was higher along with high levels of anti-thyroglobulin antibodies (TGAb: 954.3 IU/mL) and autoantibody to thyroid per-oxidase (TPOAb: 566.5 IU/mL) (Table 2). The total cholesterol level (6.34 mmol/L) and serum LDL-cholesterol (4.25 mmol/L) were also higher than normal range. Karyotyping was performed following peripheral blood lymphocyte culture. A total of 100~200 metaphase cells were analyzed by the Gbanding method. Chromosomal analysis revealed that the mosaic status for the isochromosome formation in the long arm of X, i(Xq). Her karyotype is mosaic 45,X[3]/46,X,i(X)(q10)[79]/47,X,i(X) (q10),i(X)(q10)[3]/49,X,i(X)(q10),i(X)(q10), i(X)(q10), i(X) (q10) [79] (Figure 1). This is consistent with a rare Isochromosome Xq Mosaic TS with four karyotypes. Highthroughput sequencing indicated an abnormal female karyotype. It showed that a 45.28Mb deletion in Xp22. and a 92.36Mb