What is SATB2 Associated Syndrome?
You may have seen the name “SATB2 Associated Syndrome” before, other names for this condition are “Glass Syndrome” and “2q33.1 deletion/microdeletion/mutation”.
But what does “SATB2” mean?
SATB2 is the name of the gene responsible for the rare genetic condition which is SATB2 Associated Syndrome. SATB2 is also an acronym which clinicians use to outline the main symptoms associated with this condition.
Speech and Language delays – Speech may be limited or absent
Craniofacial Abnormalities – bones of the skull (cranio) and face (facial) such as; cleft, high palate, swallowing or and feeding difficulties
Behavioural symptoms with or without bone or brain irregularities
Visible by age 2 yrs – The group of symptoms that typically surface in a child with SATB2 are more obvious after the age of two
A Brief History of SATB2 Associated Syndrome
The first reported case of SATB2 Associated Syndrome was for a 16 year old boy in 1989 diagnosed by Dr Ian Glass. At the time Dr Glass named the condition after himself calling it “Glass Syndrome”. Dr Glass identified a deletion of some genetic information in chromosome 2 (2q32.2-q33.1 microdeletion) which he determined was the cause of the condition.
Since then our understanding of SAS has grown, we now know that SAS can occur from more than one genetic change and we understand more about the condition itself. In 2003 the SATB2 gene was identified (FitzPatrick et al.) and in 2014 researchers proposed a new clinically recognisable name for the syndrome (Döcker et al.). Ideally, names of genetic conditions should be medically informative and meaningful to the condition. This is why these days we refer to the condition as SATB2 Associated Syndrome instead of “Glass Syndrome”.
The SATB2 Gene:
We can think of our genes as recipes for the body to make proteins, these proteins can be used to send messages in the body.
SATB2 gene gives the recipe to make the SATB2 protein. This SATB2 protein is incredibly important. The SATB2 gene sends messages for controlling the turning off and turning on of a network of other genes involved in development of the brain, bones, teeth, and palate. Without the SATB2 protein the body doesn’t know which of these recipes it needs to make causing a range of downstream effects.
When genetic changes in the SATB2 gene occur it can present as SATB2 Associated Syndrome. These changes can include mutations (misspellings), deletions (missing information), or duplication (extra information) in the SATB2 gene.
This is also why we see such a variable range of symptoms in people with SATB2 Associated Syndrome.
What could SATB2 Associated Syndrome mean for your loved one?
Summary for Health Professionals
SATB2 Associated Syndrome, is a genetic condition caused by a change (mutation) to the SATB2 Gene.
Whilst it is classified as rare, there are over 700 reported cases worldwide.
SATB2 Associated Syndrome is an autosomal dominant condition, however, SATB2 genetic changes are normally not inherited from either parent. This means this genetic change has occurred for the first time (De Novo) in the individual with SATB2 Associated Syndrome.
Due to the change not being inherited from a parent, it means there is a low risk (1-2%) of this genetic change occurring again in biological children.
Common clinical features of SATB2 Associated Syndrome include:
Speech anomalies – Individuals with SATB2 Associated Syndrome may have absent or limited speech.
Developmental delay and Intellectual disability – All documented cases of individuals diagnosed with SATB2 Associated Syndrome have reported developmental delay and intellectual disability. The extent of the delay can vary from person to person, however approximately half of individuals with SATB2 Associated Syndrome have severe developmental delay.
Dental anomalies – Individuals with SATB2 Associated Syndrome may experience a range of dental anomalies including abnormal shape of upper incisors, dental crowding, hypodontia (missing one or more teeth), delayed dentition (eruption of teeth occurs later than expected, may have no teeth erupted by age of 18 months), supernumerary teeth (having extra teeth), and delayed root formation. It is also common for individuals with SATB2 Associated Syndrome to regularly grind their teeth.
Palate anomalies – Approximately half of individuals with SATB2 Associated Syndrome have some form of palate anomaly. This can include cleft palate (an opening in the roof of the mouth), high palate (when the roof of the mouth rises higher than usual), bifid uvula (uvula that’s forked or split) and submucous cleft palate (an opening in the tissue covering the soft palate in the mouth).
Brain anomalies – Individuals with SATB2 Associated Syndrome may have clinical presentations of brain anomalies including: Dilated ventricles, small corpus callosum, abnormal myelination, and increased T2 white matter signals around ventricles.
Feeding issues – Majority of individuals with SATB2 Associated Syndrome experience feeding issues including oropharyngeal dysphagia (choking/gagging, overstuffing/eating). and excessive drooling.
Behaviour Issues – Younger children with SATB2 Associated Syndrome may have frequent tantrums and difficulties dealing with changes. Older individuals can be at higher risk of developing aggression towards themselves and others. Clinicians may consider Applied Behaviour Analysis and family therapy.
Sleep Issues – Individuals with SATB2 Associated syndrome can have difficulties with both falling asleep and staying asleep throughout the night. Clinicians may consider an overnight EEG sleep study if caregivers notice sleeping difficulties. Other treatments ranging from low dose melatonin to Alpha Agobnist medications may be considered by clinicians.
Less common features include skeletal anomalies (osteopenia, pectus deformities, kyphosis/lordosis, talipes, and scoliosis), growth restriction, vision issues (strabismus, refractive errors, squints), congenital heart defects, genitourinary anomalies, neurological anomalies (seizures, ataxia spasticity), and sparse thin hair.
Clinicians should be aware of the various health obstacles individuals with SATB2 Associated Syndrome encounter in order to best provide or refer on for assistance. Care teams should aim to provide integrated care to address each patients’ needs.
It is also important to note that individuals with SATB2 Associated Syndrome can have a higher than average pain threshold. Clinicians should consider this whilst providing care, as an SATB2 Associated Syndrome individual may not react in pain to indicate an injury.
Glass IA, Swindlehurst CA, Aitken DA, McCrea W, Boyd E. Interstitial deletion of the long arm of chromosome 2 with normal levels of isocitrate dehydrogenase. J Med Genet. 1989;26:127–130.
Bengani, H., Handley, M., Alvi, M., Ibitoye, R., Lees, M., Lynch, S. A., Lam, W., Fannemel, M., Nordgren, A., Malmgren, H., Kvarnung, M., Mehta, S., and 22 others. Clinical and molecular consequences of disease-associated de novo mutations in SATB2. Genet Med. 19: 900-908, 2017.
Döcker D, Schubach M, Menzel M, Munz M, Spaich C, Biskup S, Bartholdi D. Further delineation of the SATB2 phenotype. Eur J Hum Genet. 2014;22:1034–9.
FitzPatrick DR, Carr IM, McLaren L, Leek JP, Wightman P, Williamson K, Gautier P, McGill N, Hayward C, Firth H, Markham AF, Fantes JA, Bonthron DT. Identification of SATB2 as the cleft palate gene on 2q32-q33. Hum Mol Genet. 2003;12:2491–501.
A special thanks to Genetic Councillor, Rachel Muir, for working with SATB2 Connect.