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Research Article Summaries:
Below, we've summarized several research articles that include information about ANKRD11. We hope you find this information helpful! As we learn more from children who have these gene changes, we expect this list of resources and information to grow.

  • Low et al., (2016)Clinical and Genetic aspects of KBG Syndrome

    KBG syndrome is a rare disorder characterized by short stature, distinctive facial features, skeletal abnormalities, and developmental delay/ intellectual disability. Individuals with KBG syndrome had traditionally been diagnosed based on a shared clinical presentation.

    However, genetic testing can now be used to aid in the diagnostic process. In 2006, only 46 cases of KBG syndrome had been identified, but that number has grown since then as genetic testing has become more available to patients. The majority of children with a clinical diagnosis of KBG syndrome have been found to have changes in the ANKRD11 gene. This is the only gene known to be associated with KBG syndrome at this time.

    Previous studies have determined ANKRD11 genetic changes to be the cause of KBG syndrome (Sirmaci et al., 2011, summarized below) and many studies have focused on creating a list of the clinical features of this genetic change based on the number of known cases. This study considers the clinical and genetic profiles of 31 previously unreported (new) KBG patients and one adult KBG patient, who had been diagnosed with the syndrome as a child and had not previously had genetic testing. In addition to their assessment of these 32 new patients, the authors of this article also compared their analyses to the clinical information collected in other KBG studies – The researchers highlighted nine medical categories in their clinical analysis, provided here:

    v  Facial Features

    §  Similar facial features in some, but not all patients, including broad triangular face, short neck, wide or bushy eyebrows, prominent ears, bulbous nasal tip, prominent nasal bridge, long and smooth philtrum (the vertical groove between the base of the nose and the border of the upper lip), and thin upper lip.

    v  Growth

    §  Frequency of short stature among KBG patients was 40%.

    v  Perinatal Period

    §  Few complications were reported during pregnancy and all babies reached a gestation period of 36 weeks and were delivered at term with normal birthweights. 19% of babies were reported to have feeding difficulties after birth.

    v  Developmental Progress/Learning Difficulties

    §  The ages at which developmental milestones were reached was delayed. Speech was significantly delayed; most patients were between ages 2 and 3 when they spoke their first word. Mobility was also delayed, but all patients achieved walking; the oldest age to begin walking was 3 years and 2 months. 99% of the KBG patients were reported to have learning difficulties.  

    v  Neurodevelopment/Behavior

    §  43% of patients had seizures and the age at which the seizures started ranged from infancy to mid-teens. 25% had a formal diagnosis of autism spectrum disorder (ASD). Five patients had a diagnosis of attention deficit hyperactivity disorder (ADHD).

    v  Ear, Nose, Throat, and Oral Cavity

    §  Macrodontia (enlargement) of the upper incisors was seen in most of the patients recruited for this study and in 82% of the KBG patients involved in previous clinical studies. 25% of individuals had palatal abnormalities. 25% of patients had varying degrees of permanent conductive hearing loss.

    v  Skeleton

    §  Brachydactyly (shortening of the fingers or toes) and clinodactyly (curving of the fingers or toes) was reported in several patients. 22% of patients had delayed closure of the large anterior fontanelle (the bones of the front part of the skull that fuse during development).

    v  Gastrointestinal System

    §  Feeding difficulties were the most commonly seen dietary issue, affecting 25% of KBG patients, in some cases, persisting into adolescence. Gastro-esophageal reflux and severe constipation were also reported.    

    v  Other Aspects of Phenotype

    §  50% of the patients had eye abnormalities, with the most common being strabismus (any misalignment of the eyes) and refractive errors (nearsightedness, farsightedness, astigmatism, etc.). 13% of patients had congenital heart abnormalities. Many patients displayed hypertrichosis (excessive hair growth; thick hair and full eyebrows) and skin abnormalities were reported. Five patients had surgery for cryptorchidism (undescended testicles) and one patient had an inguinal (groin) hernia repair.


    The authors provide a breakdown of the most common medical concerns of note in their clinical analysis and the frequency that these were reported in KBG patients, for both their study and other KBG studies: 


    The authors also include a table with recommendations for clinical management of patients with KBG syndrome (Table II in the original article, adapted below). This may a helpful resource to bring to your child’s pediatrician, so that they can provide the best care for your child.


  • Yang et al. (2013) -- Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders
    In this study, whole exome sequencing was used to search for genetic causes to unexplained developmental delay, intellectual disability, and neurological differences in 250 children. One child had a mutation in the ANKRD11 gene that is believed to be the cause of his intellectual disability.

  • Sirmaci et al., 2011 - Mutations in ANKRD11 cause KBG Syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia

    KBG syndrome is characterized by certain types of differences with the teeth and bones. Most individuals have wide large front teeth, as well as subtle differences in bone structure that may result in subtle differences in facial features, differences in hand bones, and shorter-than-average size. Individuals with KBG syndrome are often diagnosed with intellectual disability and/or developmental delay. Some individuals have a history of seizures.

    For this publication, ten families were identified because of a diagnosis of both KBG Syndrome and autism spectrum disorder along with mild to moderate intellectual disability. Family members with and without the mutations in ANKRD11 allowed the researchers to begin to make associations between this genetic mutation and features shared by individuals with the genetic mutation.

    While little is known about the brain-related function of ANKRD11, existing research suggests that there is a high-level of ANKRD11-related activity in the brain. The authors’ conclude not only that ANKRD11 plays a very important role in development and function of the head, face, teeth, bones, and brain, but also that mutations in ANKRD11 are a cause of KBG syndrome.


You can also visit SFARI's website to see information for researchers about this gene. SFARIgene: ANKRD11

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