Table 1 Characteristics of CF, FXS, and SMA and details about genetic testing
Condition | Clinical features | Mode of inheritance and cause of condition | Treatment/management | Prevalence and carrier frequency | Carrier testing | Detection rate of carrier test |
|---|---|---|---|---|---|---|
Cystic fibrosis | Chronic suppurative lung disease, pancreatic exocrine insufficiency, blocked biliary ducts, elevated sweat electrolytes, poor weight gain, and infertility in males. | Autosomal recessive. Affected individuals have two copies of faulty CFTR gene variants, one inherited from each parent. Greater than 2,000 disease-causing CFTR variants have been identified. | No cure. Advances in treatment have led to increases in life expectancy (median survival is mid-30s) and improvements in quality of life. Pharmacological treatments currently in clinical trial phase and show promise in some cases. | 1 in 2,500; 1 in 25. Most common life-threatening recessive condition affecting Australian children. | Detection of common and severe variants in target population. | 90%a |
Fragile X syndrome | Developmental delay, intellectual disability, speech delay, autistic-like behaviors, anxiety, ADHD, epilepsy, macrocephaly, large ears, long face. Features of FXS vary from mild to severe with males more likely to be severely affected than females. | X-linked. Caused by the expansion of the CGG triplet repeat region of the FMR1 gene. FM (200 + CGG repeats) is associated with fragile X syndrome. Female FM and PM carriers are at risk of having an affected child. Female PM carriers are at risk of fertility problems and early menopause and male and female carriers are at risk of fragile X–associated tremor/ataxia syndrome. | No cure. Management through early intervention, occupational and speech therapy to address sensory defensiveness, hyperarousal, and attention problems. Tailored educational interventions. Pharmacological treatments for ADHD, anxiety, aggression, and mood instability. Clinical trials are under way for a number of drug therapies. | 1 in 4000 to 1 in 6000/1 in 250. Most common known cause of inherited intellectual disability. | Sizing of CGG repeat in 5′ region of FMR1 gene. | >99% |
Spinal muscular atrophy | Progressive muscle weakness and atrophy. Classified according to maximal functional status achieved. Type 1: never sit unsupported, onset before 6 months, marked weakness and hypotonia, areflexia, tongue fasciculations, life expectancy <2 years from respiratory failure. Type 2: sit independently but never stand or walk, onset between 6 and 18 months, proximal weakness, hand tremor, scoliosis, life expectancy >2 years to 3rd/4th decade. Type 3: stand and walk independently, onset after 18 months, may ultimately require wheelchair, life expectancy similar to normal population.b | Autosomal recessive. SMA is due to homozygous deletions of the survival motor neuron gene (SMN1) in 95% of individuals. The remainder are compound heterozygotes for the deletion and an intragenic mutation of SMN1. | Multidisciplinary management of pulmonary, gastrointestinal, nutritional, and orthopedic issues. The FDA approved the first disease-modifying therapy for SMA—nusinersen—for all forms of SMA in December 2016. | 1 in 10,000/1 in 40. SMA is the most frequent genetic cause of infant mortality. | Ascertaining SMN1 copy number. | 95% |
