Ambiguous Genitalia and Lissencephaly in A 46,XY Neonate with a Novel Variant of Aristaless Gene

Abstract

Introduction: Disorders of sexual development can present isolated or as a part of complex genetic syndromes.

Case presentation: A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2^nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent.

Conclusions: The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Keywords: ambiguous genitalia; disorders of sexual development; lissencephaly.

Figure 1.

Appearance of genitalia: microphallus, hypospadia, complete fusion of labioscrotal folds and nonpalpable gonads.