OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: TSPYL1

SIDDT

Sudden infant death
Dysgenesis of the testes
Heart and respiratory arrest
Feeding difficulties
Poor growth
Slow heart beat
Episodic cessation of breathing

Sudden Infant Death with Dysgenesis of the Testes

Clinical Characteristics

General description (for patients):

Infants with this disorder appear normal at birth but die suddenly of heart and respiratory arrest within a year.  Newborns, however, have feeding problems and may grow poorly.  They may have a brisk startle reflex induced by bright lights and loud noises, episodes of slow heart beat, and episodic cessation of breathing.  At least some infants have a “stuttering” cry that family members recognize as characteristic.  Males have intra-abdominal, maldeveloped testes, and external ambiguous genitals which may confuse gender determination.  Females have normal genitalia and normal circulating hormones.

Medical description: 

This seems to be a unique sudden death syndrome.  All affected infants, who may appear normal at birth, die within the first year of life of sudden cardiorespiratory arrest.  Many have no premonitory signs but others in the first months of life feed poorly, and may have episodes of bradycardia, hypothermia with laryngo- and bronchospasms.  Other early signs are tongue fasiculations, ocular palsies, weakness of the facial nerve, and diminished reflexes in the upper extremities.  Females appear phenotypically normal but males often have undescended testes which are variably developed.  Genital ambiguity in males may lead to gender confusion. Autopsies in 2 infants have not revealed any neuropathology.  Brainstem histology is normal and no anterior horn pathology has been found.  Cranial MRIs and EEGs have been normal.  Plasma amino acid levels are normal as are circulating hormones in females.  Not unexpectantly, fetal testosterone production is deficient.

Genetics: 

A homozygous mutation (457_458insG) that seems to be responsible for this autosomal recessive disorder has been found in the TSPYL1 gene, located on chromosome 6 (6q21-q22.31).  Note:  the TSPY protein is coded by genes on the Y chromosome and is expressed specifically in the testis.  All cases so far have been found only in the Belleville, PA, Amish population where the gene seems to be in high frequency.

Treatment:

No treatment is available.  One infant died in the hospital while on cardiac and respiratory monitoring.

Prognosis:

None have lived beyond one year of age.

Ancillary treatments and support:

None.

Specialists and specialty centers:

Pediatrician, Cardiologist, Neurologist, Urologist.

References:

Puffenberger, E.G., Hu-Lince, D., Parod, J.M., Craig, D.W., Dobrin, S.E., Conway, A.R., Donarum, E.A., Strauss, K.A., Dunckley, T., Cardenas, J.R., Melmed, K.R., Wright, C.A., Liang, W., Stafford, P., Flynn, C.R., Morton, D.H., and Stephan, D.A.:  Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function.  Proc. Nat. Acad. Sci. 101: 11689-11694, 2004.  PubMed ID: 15273283