Medicus April 2016

C L I N I C A L E D G E

CHALLENGES WITH EXPANDED SCREENING IN NON-INVASIVE PRENATAL TESTING (NIPT) Sarah Long Genetic Counsellor Genetic Services of Western Australia King Edward Memorial Hospital T he introduction of non- invasive prenatal testing (NIPT) for disorders such as trisomy 21 18 and 13

(Jacobsen syndrome), 8q (Langer-Giedion syndrome), 4p (Wolf- Hirschhorn syndrome), trisomy 16, and trisomy 22.¹¹

in Australia in 2012 has been associated with a lower rate of diagnostic tests (amniocentesis and chorionic villus sampling).¹·² Expanded NIPT screening to detect microdeletions and microduplications presents new challenges to healthcare providers and patients. Before ordering an expanded panel of screening tests, providers might ask themselves what are the potential benefits or harms offered to patients? Micro deletions and micro duplications The expanded NIPT test currently includes the five microdeletion/duplication syndromes outlined in Table 1 (below). Other conditions also being offered include 11q

Variable phenotype and penetrance The variable phenotype of several of these disorders creates difficulty. An excellent example of this is 22q11 deletion syndrome, with the clinical picture ranging from the full range of features to very little or no abnormality. Varying degrees of intellectual disability in children and adults is reported, with a proportion of affected individuals having average IQ and normal motor and speech development. Complicating matters further, approximately 5 per cent of children with a diagnosis¹² of 22q11 deletion syndrome have an affected parent who may not know they

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Table 1

Prevalence (in Caucasian population)

Expected ultrasound findings

Syndrome

Phenotype

Highly variable - no features to cleft lip/palate, congenital heart defects, hypoparathyroidism, T-cell immunodeficiency, dysmorphic features, intellectual/developmental delay, increased risk of psychiatric disorders – or minimally affected Variable but all have intellectual delay – dysmorphic features, seizures, vision problems, hearing loss, short stature, neurological anomalies, facial clefts, congenital heart defects, renal anomalies. Relatively consistent – Severe neonatal hypotonia, feeding difficulties, small genitalia (both males and females). Child onset obesity, developmental delay, short stature, dysmorphic features, behavioural problems and hyperphagia (excessive eating and food obsession). Relatively consistent – Ataxia, severe intellectual disability, speech impairment, seizures, hyperactivity and behavioural issues, autism spectrum disorder, apparently ‘happy’ affect.

Nil to congenital cardiac defects, cleft lip or palate.

22q11 deletion syndrome

1 in 4,000

1p36 deletion syndrome

1 in 5,000 -1 in 10,000

Facial clefts, cardiac defects.

Prader-Willi syndrome

1 in 10,000 - 1 in 30,000

Nil

Angelman syndrome

1 in 15,000

Nil

5p deletion syndrome (Cri du chat)

Diagnosis after soft markers on ultrasound reported but rare.³

Relatively consistent – severe intellectual and developmental delay, dysmorphic features, hypotonia, microcephaly.

1 in 15,000 to 1 in 50,000

References : ⁴ ¯ ¹º

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