Genetics and Inherited Disorders: Imprinting, Chromosomal Abnormalities & Genetic Testing Guide

pediagenosis    March 30, 2026    Health , Pediatrics , science    Comment   

Genetics And Inherited Disorders

Unusual patterns of inheritance

Imprinting: Certain genetic disorders show a phenomenon called imprinting—where the expression of the allele depends on which parent it is inherited from. For example, in Angelman’s syndrome, the abnormal deleted genes are on the maternally derived chromosome 15, but the normal paternal copy is imprinted (silenced) and so the child develops features of the disease including neurodegenerative disease, seizures, hand-flapping and an unusually happy demeanour. The same genetic material, if deleted from the paternal chromosome 15, with the maternal genes imprinted, leads to Prader– Willi syndrome, with neonatal hypotonia and feeding difficulties, developmental delay and later onset obesity and delayed sexual development.

In Beckwith – Wiedermann syndrome (neonatal hyperinsulinism, macroglossia and macrosomia), there is often uniparental disomy of Chromosome 11, with the maternally derived chromosome 11 replaced with an extra paternal copy. This leads to abnormal expression of IGF2 (insulin like growth factor) gene. About 85% of Beckwith – Wiedermann cases are sporadic.

Some autosomal dominant disorders such as congenital myotonic dystrophy (type 1) show a phenomenon called genetic anticipation. That is, the disease tends to present earlier, or with a more severe phenotype, in each successive generation. In the case of myotonic dystrophy, this is due to increasing numbers of abnormal CTG base triplet repeats in a gene on chromosome 19. Many hundreds of repeats of this sequence can be found.

Chromosomal disorders

Chromosomal disorders are usually sporadic due to non-disjunction of chromosomes during the first or second meiosis (trisomy 21, 18 or 13) of gamete formation (Figure 8.1). This means there are two copies of a chromosome in some eggs and with a third from the sperm triploidy results. Triploidy of the larger chromosomes is usually lethal but 13, 18 and 21 can survive. Chromosome 21 is actually the smallest chromosome (number 22 was mislabelled!) and so there is less disruption of genetic material and people with trisomy 21 (Down syndrome) can survive into adulthood. The extra chromosome is seen in a karyotype test (Figure 8.2). Trisomies are more common with advanced maternal age. As well as occurring by non-dysjunction, trisomy can occur due to a ‘balanced translocation’, where material from one chromosome is attached to another, so that with fertilization an embryo can end up with three copies of the same part of one of the chromosomes. This can be inherited and so if found it is important to check parental karyotype also.

Chromosomal disorders can also be due to deletion of an entire chromosome e.g. loss of an X chromosome leads to 45 XO (Turner’s syndrome) with short stature, webbed neck, as risk of coarctation of the aorta and infertility due to ovarian dysgenesis. Other sex chromosome anomalies include 47XXY (Klinefelter’s syndrome with tall stature and hypogonadism). Sometimes, only part of a chromosome is deleted, for example, 5p-, where the short arm of chromosome 5 is missing, leads to cri-du-chat syndrome with a characteristic cat-like cry as a baby, cognitive delay and behavioural problems.

Testing for genetic disorders

Most disorders that are screened for in newborns have a genetic basis. Molecular genetic techniques are increasingly used to identify abnormal genes or chromosomes. It is vital that families receive appropriate counselling so that they understand the implications of an abnormal result. Genetic tests can be performed at various times (see Chapter 7):

•   Pre-implantation testing is only available with in vitro fertilization techniques but can allow screening prior to implantation.

•   Antenatal genetic testing via chorionic villus sampling or amniocentesis allows the possibility of termination of pregnancy. Some families choose to continue the pregnancy despite a positive result and this allows them time to come to terms with the diagnosis.

•  Newborn genetic testing may be performed to confirm a clinical diagnosis (e.g. Down’s syndrome or congenital myotonic dystrophy) or following a positive screening test (e.g. CF gene testing following an abnormal IRT result on the newborn blood spot screen).

•   Genetic testing of older children may be needed to confirm a diagnosis presenting later in childhood (e.g. fragile X or Duchenne muscular dystrophy). In general, children should not be tested for adult-onset genetic disorders without their own informed consent unless it is going to alter their treatment during childhood.