46,xy Gonadal Dysgenesis, Partial, With Minifascicular Neuropathy

A number sign (#) is used with this entry because 46,XY partial gonadal dysgenesis with minifascicular neuropathy may be caused by mutation in the desert hedgehog gene (DHH; 605423).

Mutations in the DHH gene have also been found in patients with 46,XY complete gonadal dysgenesis who do not have minifascicular neuropathy.

Clinical Features

Umehara et al. (1999) described a patient with 46,XY partial gonadal dysgenesis associated with polyneuropathy. The diagnosis was made on the basis of female external genitalia with a blind vagina and immature uterus, presence of a testis on one side and a streak gonad on the other, and 46,XY karyotype. A particular feature was the presence of extensive formation of minifascicles within the endoneurium of the sural nerve. Each minifascicle contained several axon-Schwann cell units that were separated by one to several layers of flattened cell processes with the morphology of perineurial cells, which are normally found surrounding large nerve fascicles.

Sugie et al. (2002) reported a case similar to that of Umehara et al. (2000). A 47-year-old phenotypically female patient who presented with polyneuropathy was found to have pure gonadal dysgenesis, characterized by poorly developed secondary sex characteristics, a blind vagina, bilateral streak gonads, and 46,XY karyotype. Sural nerve biopsy showed minifascicle formation. The patient's parents were first cousins.

Molecular Genetics

The combination of manifestations reported by Umehara et al. (1999) suggested that a mutation in a gene that is involved in both male gonadal differentiation and perineurial development might be responsible for this syndrome. Umehara et al. (2000) thus investigated the DHH gene in this patient and her family. The proband was found to have a homozygous missense mutation at the initiating codon in exon 1 of the DHH gene (605423.0001), which predicted a failure of translation.

Sugie et al. (2002) performed molecular analysis on their patient and detected no mutations in the DHH gene or the SRY gene (480000). They suggested that another common factor is involved in this particular phenotype of GD and neuronal differentiation.