16p13.11 microdeletions

See https://childnervoussystem.blogspot.com/2017/02/16p1311-microdeletion.html

Inspired by a patient

Many babies with a 16p13.11 microdeletion are born completely healthy. Others have a birth defect which can be quite minor or more serious. Most of the birth defects reported among babies with 16p13.11 microdeletion have only occurred in just a few babies, so they may be a coincidence, and it is still not clear if all of the birth defects reported here are actually caused by the 16p13.11 microdeletion. 

However, one common finding is that on investigation, 17 people with the microdeletion 8 have some anomaly of the brain structure that shows on magnetic resonance imaging (MRI). Various anomalies have been detected and there appears to be no consistent feature. 

Children and adults with the microdeletion may have hands that are not perfectly formed. One child has fingers which are fused (syndactyly). Two children have fingers which do not fully straighten. These features do not usually cause medical problems but in some cases do have an impact on functionality. 

The feet of children with 16p13.11 microdeletions may also not be perfectly formed. One child had rocker bottom feet. He had serial casting on his feet for 6 weeks from birth which brought his feet into the correct position. He then wore special boots for 23 hours a day for 4 months to maintain the correct position. He will continue to wear his boots at night until he is 4 years old (he is now 3½). Another has feet that pronate (roll inwards) and wears ankle foot orthotics (AFOs) on both feet to correct her foot position and help her to bear weight. 

In five babies the heart was affected: three babies had small holes in the heart which all resolved spontaneously and needed no treatment. Another baby had cardiomegaly (an enlarged heart) at birth but on follow-up at 3 months the heart was normal. Another baby had hypertrophic cardiomyopathy (the muscle of the heart is thickened) which needed no intervention. Two baby boys were born with undescended testes and one had a very small penis (micropenis). One baby boy was born with hypospadias, where the opening usually at the end of the penis is on the underside, generally corrected with surgery. 

Two babies had brachycephaly (a flat head) which necessitated wearing a cranial helmet (Unique). 

One baby was born with a cleft palate (an opening in the roof of the mouth, usually closed surgically). 

In one baby the kidneys and drainage system for urine were affected. One baby was born with a hollow chest (pectus excavatum). 

One girl had a urethral caruncle for a short period which resolved itself. A urethral caruncle is a soft, fleshy protrusion of the urethral lining from the urethral opening. The urethra is the tube that drains urine from the bladder. One baby had a twisted neck (torticollis)…

In general children with a 16p13.11 microdeletion are happy, kind, affectionate and social. However, they are as vulnerable to frustration as other children with a communication difficulty and a small minority succumb to temper tantrums and aggression. One adult described in the medical literature was very talkative with intermittent verbal aggression and self-mutilation. 

Autistic traits or autistic spectrum disorder (ASD) have also been reported in several people with a 16p13.11 microdeletion. A diagnosis of autism can be extremely helpful in accessing services and tailoring the educational and behavioural therapy to meet the specific needs of a child with autism. Two children find socialising difficult, one of whom has been diagnosed with an anxiety disorder. Four children have obsessive compulsive disorder (OCD), an anxiety-related condition in which people experience frequent intrusive and unwelcome obsessional thoughts, often followed by repetitive compulsions, impulses or urges. Sensory issues have also been reported to affect four children. One person has Tourette syndrome (a neurological disorder characterized by repetitive, stereotyped, involuntary movements and vocalisations called tics). 

One person in the medical literature is described as having psychotic depression (depression accompanied by hallucinations and delusions) which developed after the onset of epilepsy and another has psychosis (a condition that affects a person’s mind and causes changes to the way that they think, feel and behave and can result in an inability to distinguish between reality and imagination) which is controlled with medication…

A 16p13.11 microdeletion is tiny, so it can only be found using molecular techniques such as MLPA or microarrays (array-CGH) or targeted cytogenetic testing using FISH. These techniques show whether particular genes are present or not. The features of a 16p13.11 microdeletion are likely to be a result of the loss of a number of different genes found in this region. The typical 16p13.11 microdeletion is 1.65Mb and encompasses around 15 genes. Some people have a slightly larger deletion, however, it seems that these people have the same features as those with the smaller, typical microdeletion. NDE1 which is expressed in the brain has been postulated to be responsible for the microcephaly that is often seen in those with a 16p13.11 microdeletion. 

Mutations in NDE1 in humans have been shown to cause microcephaly. Mice missing this gene have a small brain. 

NTAN1 is a candidate for some of the features of a 16p13.11 microdeletion. Mice missing this gene have altered social behaviour and memory. 

It is important to remember that while identifying the gene(s) responsible for certain features of a 16p13.11 microdeletion is valuable and may help guide future studies, it does not lead directly to immediate improved treatment. Additionally, even if the supposedly responsible gene is missing it does not always mean that the associated feature(s) will be present. Other genetic and environmental factors often have a role in determining the presence or absence of a particular feature.

http://www.rarechromo.org/information/Chromosome%2016/16p13.11%20microdeletions%20FTNW.pdf