Sudden Infant Death With Dysgenesis Of The Testes Syndrome

A number sign (#) is used with this entry because SIDDT is caused by mutation in the testis-specific protein-like-1 gene (TSPYL1; 604714).

Clinical Features

Puffenberger et al. (2004) identified a previously unrecognized syndrome, termed sudden infant death with dysgenesis of the testes (SIDDT), in 21 individuals from 9 sibships among the Belleville Old Order Amish community. The condition was not seen among the Lancaster County Old Order Amish population. Affected infants appeared normal at birth, but developed signs of visceroautonomic dysfunction early in life followed by death before age 12 months of abrupt cardiorespiratory distress. Features included bradycardia, hypothermia, severe gastroesophageal reflux, laryngospasm, bronchospasm, and abnormal cardiorespiratory patterns during sleep. Postmortem examination of 2 infants showed no neuropathologic abnormalities; specifically, the brainstem and anterior horn cells were normal. Genotypic males with SIDDT had fetal testicular dysgenesis and ambiguous genitalia, with findings such as intraabdominal testes, dysplastic testes, deficient fetal testosterone production, fusion and rugation of the gonadal sac, and partial development of the penile shaft. Female sexual development was normal. Affected infants had an unusual staccato cry, similar to the cry of a goat.

Mapping

Using a high-density SNP genome scan, Puffenberger et al. (2004) localized the SIDDT disease locus to a 3.6-Mb interval on chromosome 6q22.1-q22.31 (maximum 2-point lod score of 2.41).

Molecular Genetics

In 21 affected patients with SIDDT, Puffenberger et al. (2004) identified a homozygous mutation in the TSPYL1 gene (604714.0001). All parents of affected infants were heterozygous for the mutation, and no unaffected sibs were homozygous for the mutation.