Differences of Sex Development (DSD) are a common congenital condition with an estimated frequency of 1%. However, 50% of cases remain undiagnosed genetically.
Aims: To report a patient with a 46,XY DSD and an overgrowth syndrome of unknown genetic etiology.
Methods: Clinical phenotype was examined and hormonal profile was evaluated. DNA was extracted for whole exome sequencing.
Results: A 13-year-old Mexican patient with a 46,XY DSD and an overgrowth syndrome. Atypical genitalia was diagnosed since birth characterised by micropenis, subglandular hypospadias, bilateral inguinal cryptorchidism, and hypoplastic scrotum. Müllerian ducts were absent by ultrasonography. Hormonal evaluation at 9 years of age revealed hypergonadotrophic hypogonadism. When the patient was ten months old, tall stature and a developmental delay were detected followed by accelerated growth velocity and advanced bone age. The patient also presented with camptodactyly of the third, fourth, and fifth finger, submucous cleft palate, speech delay and mild intellectual disability. Facial dysmorphic features include broad forehead, hypertelorism, down slanting palpebral fissures, wide nasal bridge, long philtrum and large ears. Brain magnetic resonance imaging showed periventricular hyperintensities and enlargement of the subarachnoid space.
Among overgrowth syndromes, facial dysmorphisms and intellectual disability are commonly shared while camptodactyly and advanced bone age are unique features of Weaver/Weaver-like syndrome. However, the co-occurrence of Weaver like syndromes with atypical genitalia including micropenis and hypospadias has not been reported yet. WES analysis revealed no pathogenic or likely pathogenic variants among 82 known and candidate DSD target genes, as well as PRC2 complex genes (EZH2, EED, SUZ12).
Conclusion: The patient with a 46,XY DSD and an overgrowth syndrome remains genetically undiagnosed by this initial evaluation. Therefore, differential diagnoses should be considered, and a further molecular/genetic analyses are underway.