Spinal muscular atrophy (SMA) is a group of autosomal recessive neuromuscular disorders and is the most common cause of genetically determined neonatal death. The affected person will have muscle weakness and atrophy due to loss of the motor neurons in the spinal cord and brainstem. The incidence of the disease is approximately 1 in 6,000 to 1 in 10,000 live births. Importantly, approximately 1 in 40 American people are carriers.

In 1995, the SMA-causing gene, termed the survival motor neuron (SMN), was discovered. Each individual has 2 SMN genes, SMN1 and SMN2 located on chromosome 5q12.2-13.3. The most common form of SMA is caused by mutation or deletion of SMN1 gene. There are 4 types of SMA depending on the age of onset, the maximum muscular activity achieved and survival i.e.

• Type I ; severe infantile acute SMA or Werdnig-Hoffmann disease. Infants with SMA1 experience severe weakness before 6 months of age. Most affected children die before 2 years of age but survival may depend on the degree of respiratory function and respiratory support.
• Type II ; infantile chronic SMA is characterized by having disease onset usually between 3 and 15 months and has survival beyond 4 years of age and usually until adolescence or later.
• Type III ; juvenile SMA (Wohlfart-Kugelberg-Welander disease), has disease onse usually between 2 and 17 years of age.
• Type IV ; adult onset SMA, the median age of disease onset is 35 years, and the mean age at initial symptom presentation is 37 years. In order to be diagnosed with SMA, symptoms need to be present. In most cases a diagnosis can be made by the SMN gene test. In some cases, when the SMN gene test is not possible or dose not show any abnormality, an electromyography (EMG) or muscle biopsy may be indicated.

Figure 1 illustrate an autosomal recessive inheritance pattern : When both parents are unaffected for the disorder and carries the faulty gene copy ‘blue’, then there is 25% chance that the child will inherit both of the faulty genes copy and will therefore be affected by the disease. From : http://ghr.nlm.nih.gov/handbook/illustrations/autorecessive.jpg

As it is an autosomal recessive genetic disease. In order for a child to be affected by SMA, both parents must be carriers ofabnormal gene and both must pass the affected genes to their child. When both parents are carriers, the likelihood of their child being affected with disorder is 25%, or 1 in 4 (ffi igure 1).

However, SMA is one of the single gene disorders that Superior A.R.T. can provide a preimplantation genetic diagnosis based on polymerase chain reaction (PGD-PCR) to exclude the embryos affected with the disease. Therefore, only the disease-free embryo(s) will be transferred to the uterus for further implantation. Commonly, PGD is used when a couple is aware of the possibility that their offspring will inherit a genetic disease.

Where a couple is interested in PGD for detecting a single gene disorder, you can refer the patient with the following protocol. The fif irst step for of PGD-PCR procedure is specifif ic test kit preparation. The important information required for test kit preparation are ;

• Mutation reports of the couples and / or affected family members.
• Blood samples or DNA sample of the couples and/or affected family members.

The procedure for test kit preparation :

1. Clinician with a clinical geneticist or genetic counselor will arrange a consultation to a couple regarding steps of ICSI/PGD-PCR procedures.
2. A couple will be interviewed by a PGD scientist for family history and family pedigree. The PGD scientist will assess a feasibility of test kit preparation from mutation report and indicate the appropriate blood samples to be collected from family members for test kit preparation.
3. Collect blood samples from the couple and relevant family members. This should either be a) 3-4 ml blood collected in an EDTA tube or, b) blood collected onto a blood card. In some circumstances a buccal sample (mouth swab) may be collected.
4. The test kit preparation will commence when PGD scientist has received all necessary mutation reports and blood samples. The test kit preparation normally takes 8-10 weeks to complete.
   * The patient should be informed that no stimulation can commence until the completion of test kit preparation *
5. PGD scientist or nurse coordinator of Superior A.R.T. will notify clinician and patient at the completion of test kit preparation. Following this, ovarian stimulation can commence.
6. Please notify nurse coordinator at Superior A.R.T. immediately when the stimulation cycle has started, in order to prepare case setting-up. Furthermore, you can bring your patient to Superior A.R.T. to start stimulation cycle.
7. If a patient will get started with subsequent PGD-PCR cycles, PGD scientist at Superior A.R.T. should be notifif ied at least 2-3 weeks before the initiation of ovarian stimulation. The scientist will verify the amount of test kit availability. If it is insufficient, a new test kit will be prepared and tested with no additional cost.

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