Williams syndrome

Williams syndrome, also called Williams-Beuron syndrome, is a rare genetic disorder caused by the deletion of a segment of chromosome 7, called 7q11.23, that includes about 28 genes1.

Children with Williams syndrome have a range of cognitive symptoms, including a happy and highly social demeanor, developmental delay and strong language skills. They also have cardiovascular symptoms and facial dysmorphology, such as a small nose with a flattened bridge, and a small chin.

Implicated genes:

In a 2011 study, researcher engineered a mouse model lacking one copy of GTF21, a gene included in the Williams syndrome region.

GTF2I is one of a handful of genes that researchers consider to be key players in Williams syndrome. The protein it encodes is a transcription factor, affecting the expression of other genes, but its precise role is unknown.

Control mice are interested in novelty — they eagerly investigate a new mouse or object placed in their cage. Once they’ve sniffed around a bit and the item becomes familiar to them, they lose interest, a process known as habituation.

When the GTF2I-deficient mice are shown a familiar object and a new object, however, they’re equally interested in both. And when a new mouse is introduced into their environment, they don’t habituate as rapidly as control mice do.

More than one gene may contribute to social abnormalities in the disorder. For example, a study published in October 2010 found that mice lacking a protein called PSD-95 are more social than controls. These mice also express about 50 percent less of CYLN2 a gene in the Williams syndrome region, compared with controls2.

Presented with a choice between exploring a room with an empty cage in it or a room with a cage holding a mouse inside, the PSD-95 mutant mice choose the room with the playmate. In fact, they spend even more time with the new mouse than do controls.

Language:

Prevailing wisdom says that Williams syndrome severely diminishes spatial and mathematical reasoning, while leaving language skills intact. A 2010 study, however, reports that children with the syndrome do not understand passive sentences that use abstract verbs, such as ‘love’ or ‘remember’3.

Relevance to autism:

In some ways Williams syndrome is the opposite of autism. For example, people with Williams syndrome love to talk and tell stories, whereas those with autism usually have language delay and little imagination. Many people with Williams syndrome draw disjointed pictures, some with autism draw pictures in perfect detail. Infants with Williams syndrome stare at other people’s eyes and babies with autism avoid eye contact.

However, several individuals with Williams syndrome are also diagnosed with autism. This suggests that they share an underlying mechanism and understanding one disorder can shed light on the other.

Children with a duplication in the Williams syndrome region have some autism-like features4. Like children with autism, they struggle to speak and lag years behind their typical peers in language production.

There is also crossover between the genes implicated in each disorder. GTF21 interacts with DLX5 and DLX6, transcription factors implicated in autism5. The DLX genes are involved in the formation of neurons that release the neurotransmitter GABA, and may have a connection to the imbalance between neuronal excitation and inhibition seen in autism.

In October 2010, the Williams Syndrome Association hosted a symposium that included a discussion of the overlap between Williams syndrome and autism.


References:
  1. Sakurai T. et al. Autism Res. Epub ahead of print (2010) PubMed
  2. Feyder M. et al. Am. J. Psychiatry 167, 1508-1517 (2010) PubMed
  3. Perovic A. and K. Wexler J. Speech Lang. Hear. Res. 53, 1294-1306 (2010) PubMed
  4. Van der Aa N. et al. Eur. J. Med. Genet. 52, 94-100 (2009) PubMed
  5. Poitras L. et al. Development 137, 3089-3097 (2010) PubMed
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