Homozygous deletion in the SMN1 gene in asymptomatic individual - genetic counselling issues in SMA-risk families.

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders. The mode of inheritance of SMA is what determines the relatively low risk to off spring of affected persons, sibs of carriers of the pathogenic mutation or their more distant relatives. Nonetheless, the risk in question is increased beyond that in the population in general, thereby indicating the need for preventative measures to be taken in respect of SMA families. We present clinical characteristics of such a SMA-risk family. An apparently unaffected brother (patient) of the proband together with his pregnant wife sought genetic counselling about the SMA risk in their off spring. The estimated a priori risk was of about 0.5% (1 in 200). Molecular diagnostic tests performed in the patient indicated the presence of a homozygous deletion of the SMN1 gene identical to the one detected in the affected proband. The patient's wife was identified as a carrier of the deletion. The conditional risk for off spring of the couple was thus recalculated as 50% (1 in 2). Homozygous deletion of the SMN1 gene in unaffected individuals is a relatively rare event, yet one that nevertheless has significant impact on genetic counselling in SMA families. In these circumstances, molecular confirmation of SMA in such families allows for the provision of competent and reliable genetic advice, as well as for the introduction of secondary preventative measures. It also meets inclusion criteria as regards optional invasive prenatal diagnostic testing in families with a high (.25%) risk of the condition being present in the off spring.