LEARNING DISABILITY
(GENERAL LEARNING DISABILITY/ INTELLECTUAL DISABILITY)
A neurodevelopmental condition, with onset in the developmental period (before the age
of 18), which is characterized by impaired intellectual functioning (learning, problem-solving,
judgement etc.), and limitations in adaptive behaviours (independent living activities,
communication and social skills etc.) (Patel et al. 2020).
COMMON GENETIC & NON-GENETIC AETIOLOGICAL FACTORS OF LD
Learning disability (LD) is multicausal.
GENETIC AETIOLOGICAL FACTORS:
• ANEULIPIDIES (missing or extra chromosomes); most common form is TRISOMY
• TANDEM REPEAT POLYMORPHISIMS (TRPs)
• COPY NUMBER VARIATIONS (CNVs) etc.
(Ilyas et al. 2020)
The 2 most common genetic causes of LD are Down’s and Fragile X syndromes.
➢ DOWN SYNDROME
This chromosomal disorder, first described by John Langdon Down in 1866, is the most
common genetic cause of LD.
DS is predominantly- in about 95% of the cases- caused by NONDISJUNCTION; an error in cell
division which leads to an extra copy of chromosome 21. This form of DS is sometimes called
TRISOMY 21 (Asim et al. 2015). The incidence of meiotic nondisjunction increases with
maternal age.
In approximately 3% of cases, DS is caused by ROBERTSONIAN TRANSLOCATION where a
segment (the long arm) of chromosome 21 attaches to another chromosome (generally
chromosome 14 or 15). This type of DS is sometimes called FAMILIAL DOWN SYNDROME, as
translocations might be inherited. Chances of transmission: father as carrier (roughly 3%),
mother as carrier (10-12%) (Kazemi et al. 2016). However, Robertsonian translocations are
1
, not always passed down genetically from parent to child, they can occur de novo (Kusre et al.
2015).
MOSAICISM is an extremely rare cause of DS accounting for less than 1% of all cases (Kazemi
et al. 2016). MOSAIC DOWN SYNDROME is very similar to Trisomy 21, however, in these cases
the third copy of chromosome 21 is only present in some and not all cells.
Individuals with DS tend to have:
• small stature
• slanted eyes
• flat nasal bridge
• small chin
• small mouth
• large tongue
• hypotonia (decreased muscle tone)
Some medical conditions such as cardiac problems/heart defects, hematologic disorders including
leukemias are more common in people with DS than in the general population. There is also an
increased risk of Alzheimer’s disease. It is estimated that about 70% of individuals with DS over the
age of 50 will develop the disease (Asim et al. 2015).
➢ FRAGILE X SYNDROME (MARTIN BELL SYNDROME):
FXS is the most common cause of inherited LD and second only to DS as the most common
genetic cause of LD.
It most often results from an X chromosome gene mutation; abnormal expansion of a
trinucleotide repeat (CGG) in the fragile X mental retardation 1 (FMR1) gene. Males are
generally more severely affected. Due to compensation by the unaffected X chromosome,
only about 30-50% of female carriers with a full mutation will develop general learning
disability (Bagni et al. 2012). However, specific learning difficulties as well as emotional
problems are still rather common among such individuals (Davey 2014).
Most common physical characteristics associated with FXS:
• elongated face
• prominent ears
2
(GENERAL LEARNING DISABILITY/ INTELLECTUAL DISABILITY)
A neurodevelopmental condition, with onset in the developmental period (before the age
of 18), which is characterized by impaired intellectual functioning (learning, problem-solving,
judgement etc.), and limitations in adaptive behaviours (independent living activities,
communication and social skills etc.) (Patel et al. 2020).
COMMON GENETIC & NON-GENETIC AETIOLOGICAL FACTORS OF LD
Learning disability (LD) is multicausal.
GENETIC AETIOLOGICAL FACTORS:
• ANEULIPIDIES (missing or extra chromosomes); most common form is TRISOMY
• TANDEM REPEAT POLYMORPHISIMS (TRPs)
• COPY NUMBER VARIATIONS (CNVs) etc.
(Ilyas et al. 2020)
The 2 most common genetic causes of LD are Down’s and Fragile X syndromes.
➢ DOWN SYNDROME
This chromosomal disorder, first described by John Langdon Down in 1866, is the most
common genetic cause of LD.
DS is predominantly- in about 95% of the cases- caused by NONDISJUNCTION; an error in cell
division which leads to an extra copy of chromosome 21. This form of DS is sometimes called
TRISOMY 21 (Asim et al. 2015). The incidence of meiotic nondisjunction increases with
maternal age.
In approximately 3% of cases, DS is caused by ROBERTSONIAN TRANSLOCATION where a
segment (the long arm) of chromosome 21 attaches to another chromosome (generally
chromosome 14 or 15). This type of DS is sometimes called FAMILIAL DOWN SYNDROME, as
translocations might be inherited. Chances of transmission: father as carrier (roughly 3%),
mother as carrier (10-12%) (Kazemi et al. 2016). However, Robertsonian translocations are
1
, not always passed down genetically from parent to child, they can occur de novo (Kusre et al.
2015).
MOSAICISM is an extremely rare cause of DS accounting for less than 1% of all cases (Kazemi
et al. 2016). MOSAIC DOWN SYNDROME is very similar to Trisomy 21, however, in these cases
the third copy of chromosome 21 is only present in some and not all cells.
Individuals with DS tend to have:
• small stature
• slanted eyes
• flat nasal bridge
• small chin
• small mouth
• large tongue
• hypotonia (decreased muscle tone)
Some medical conditions such as cardiac problems/heart defects, hematologic disorders including
leukemias are more common in people with DS than in the general population. There is also an
increased risk of Alzheimer’s disease. It is estimated that about 70% of individuals with DS over the
age of 50 will develop the disease (Asim et al. 2015).
➢ FRAGILE X SYNDROME (MARTIN BELL SYNDROME):
FXS is the most common cause of inherited LD and second only to DS as the most common
genetic cause of LD.
It most often results from an X chromosome gene mutation; abnormal expansion of a
trinucleotide repeat (CGG) in the fragile X mental retardation 1 (FMR1) gene. Males are
generally more severely affected. Due to compensation by the unaffected X chromosome,
only about 30-50% of female carriers with a full mutation will develop general learning
disability (Bagni et al. 2012). However, specific learning difficulties as well as emotional
problems are still rather common among such individuals (Davey 2014).
Most common physical characteristics associated with FXS:
• elongated face
• prominent ears
2
