en-us-5q14.3 Deletion

03/04/2017

A deletion is a type of anomaly or chromosomal disorder characterized by the total or partial loss of a segment of the chromosome. This genetic alteration is related with a variety of consequences since each chromosome carries an important range of genes, each one of them responsible for transmitting essential information for the development and the growth of the individual. 

5q14.3 Deletion

Faced with the diagnosis of a rare chromosomal disorder, the limitation or even lack of vailable information about the condition is evident. There are so many different types of chromosomal alterations that it is unlikely that there will be a considerable number of people with exactly the same result. Since the group of people diagnosed is restricted, it is difficult to predict how the chromosome disorder will affect their health.
Defects in chromosomes, from 1 to 22 are known to be usually more severe than those in the X and Y sex chromosomes, such as in Turner syndrome, for example, in which the woman has only one X chromosome.
5q14.3 Deletion is a rare chromosomal disorder, with few cases reported worldwide and with a very large variation in the way the deletion affects each individual. Depending on the size of the deletion, the amount and types of genes affected, and the early stimuli that will be offered to the carrier, the characteristics and patterns of development may fluctuate greatly. Some characteristics, however, appear to predominate in most cases.

In the case of the 5q14.3 deletion syndrome, the loss of genetic material occurs on chromosome 5, long arm (q) and band 14.3. One of the genes normally affected in this stretch of the chromosome is MEF2c gene, responsible for most of the symptoms reported among patients diagnosed with this deletion.

Most common physical features (dysmorphisms) include:

  • High and wide front
  • Low nasal bridge, small nose and nostrils
  • The upper lip in the shape of a "cupid bow" with the short and well marked philtrum
  • Small chin
  • Oblique palpebral fissure
  • Sloping mouth corners
  • Relatively wide ears
  • Long fingers
  • Short neck

Aspects of development:

  • Severe and early hypotonia (low muscle tone)
  • Severe cognitive delay
  • Global Development Delay
  • Low visual contact and limited hearing response.
  • Seizures
  • Stereotyped movements
  • Delayed speech or inability to communicate through speech.

Other less frequent or less frequently mentioned features in the medical literature include:

  • Dysphagia (Difficulty of swallowing)
  • Constipation
  • Gastroesophageal reflux disease
  • Inappropriate laughter (for no apparent reason)
  • Impaired social reciprocity or limited engagement with or recognition of other people.
  • High pain tolerance
  • Irregular sleep

Despite the disabilities associated with the 5q14.3 deletion syndrome, some families report considerable advances in the development of affected children and emphasize the importance of interdisciplinary support of stimulus therapies such as Physical Therapy, Speech Therapy and Occupational Therapy. The support and encouragement of the family and the people who live with the child are also extremely important in advancing and acquiring new skills. It is important, in spite of your child´s apparent lack of reactions, that he/she is inserted in the family´s routine and that this interaction offers them a variety of learning experiences.
One of the most frequent questions and concerns among parents is the possibility of reversal of the chromosomal abnormality. Although there are ongoing studies on genome editing techniques, there is still no treatment or technology that enables this type of intervention. When a chromosomal anomaly occurs as the 5q14.3 deletion, the "defect" that the chromosome carries repeats in billions of affected cells, which would require the genetic manipulation of each of these cells.
There are, however, many treatment alternatives for the symptoms of the syndrome and many possibilities to stimulate the development of the affected individuals so that they have a good quality of life and reach their maximum potential. 



References

  • Carr CW, ZimmermanHH, Byrd AC, Martin CL, Vikkula M, Abdul-Rahman OA.2011. 5q14.3 Neurocutaneous syndrome: A Novel contiguous gene syndrome caused by a simultaneous deletion of RASA 1 and MEF2C . Am J Med Genet Part A 155:1640-1645
  • MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways. Neurogenetics 2013
  • Unique, Understanding chromossome disorders.5q14.3 Deletion Guide. Disponível em https://www.rarechromo.org/html/DisorderGuides.asp. Acesso em 18 de Novembro de 2016
  • Genetic and Rare Diseases (GARD) Information Center disponível em https://rarediseases.info.nih.gov. Último acesso em 18 de Novembro de 2016