ATR-16 Syndrome

Imagine this scenario. A child has serious deficits in learning abilities, act like they are in their world, and cannot adequately process what somebody asks them to do. If the guess is autism, that is right. However, ever wonder what might be a probable reason for this disorder?

What is the Meaning of ATR−16 Syndrome?

Dr. Weatherall et al. published the first account of the unusual association between alpha thalassemia and cognitive disability in the scientific literature in 1981. Since that initial description, two different disorders have been identified in the medical literature through additional case reports. ATR−X syndrome, also known as alpha thalassemia X−linked intellectual impairment, is one.

In people with ATR−16 syndrome, a very rare genetic condition, there is a drastic decrease in genetic information (monosomy) on chromosome 16, and other nearby genes are deleted. Intellectual disability, clubfoot, microcephaly, a smaller−than−expected head circumference for an infant's age and gender, and alpha thalassemia, a blood condition marked by low amounts of functional hemoglobin, are among the symptoms.


Researchers have had trouble identifying a distinct syndrome with defining "core" symptoms, and many aspects of the condition are still not fully understood. It might be challenging to distinguish which symptoms are related to which chromosomal anomaly because, in many cases, there are additional chromosomal abnormalities in conjunction with the loss of chromosome 16. Additionally, doctors cannot establish a comprehensive picture of the related symptoms and prognosis because of the low number of confirmed cases, the absence of significant clinical investigations, and the likelihood that additional genes may influence the condition. It should be no surprise that each person would experience ATR−16 syndrome differently in terms of the specific symptoms and intensity. On the other hand, it is evident that the more genetic material lost from chromosome 16, the more serious the results.

Alpha thalassemia, anemia characterized by unusually small (microcytic) red blood cells deficient in functional hemoglobin, affects infants with ATR−16 syndrome. With ATR−16 syndrome, the anemia is typically mild, asymptomatic, and frequently discovered incidentally.

Children with ATR−16 syndrome often experience intellectual handicaps, ranging from mild to moderate. As the affected kid ages, developmental and verbal difficulties become more noticeable. Seizures have been observed less frequently. An infant's head circumference may be less than predicted, given their age and gender (microcephaly). Short stature, or children who are smaller than anticipated in their age and gender, can be caused by growth delays.

Larger deletions of genetic material in infants with ATR−16 syndrome may also result in other distinctive facial characteristics, such as eyes that are more distant from one another than normal (hypertelorism), straight down palpebral fissures (meaning the entryways between the eyelids slant downward), a broad, notable nose bridge, small ears, a receding chin (retrognathia), and a short neck. In some circumstances, skeletal deformities like clubfoot (talipes equinovarus) and pinkies that are cemented or "locked" in a bent position may manifest.


On chromosome 16, several genes close to one another are affected by the removal or ablation of genetic material, which results in ATR−16 syndrome. Protein−building instructions are provided by genes, which are essential for numerous bodily processes. A gene mutation might result in the production of a protein that is defective, ineffective, or non−existent. This can have an impact on a variety of body organ systems, including the brain, depending on the precise roles of the individual protein.

Many people have an extrachromosomal anomaly or abnormalities, which causes the vast range of symptoms that have been recorded. In some instances, a symmetrical chromosomal inversion in one of the parents may cause ATR−16 syndrome. The parental rearrangement is typically referred to as a "balanced translocation."

Clinical Features

Alpha−thalassemia patients (usually) may display a modest to substantial intellectual impairment. Rarely, patients may have moderate general dysmorphic characteristics, such as hypertelorism (wide eyes), down slanting eyes, a broad or visible nasal bridge, little ears with a short neck, microcephaly (small head), and low stature. Other anomalies include clubfoot and genital alterations.


Identification of the distinctive symptoms, a thorough review of the patient's medical history, a careful clinical assessment, and several specialized tests all contribute to the diagnosis of ATR−16 syndrome.

Clinical Testing and Workup

When ATR−16 syndrome is linked to a chromosomal anomaly like a translocation, routine cytogenetic studies can be used to diagnose the condition. The G−band analysis, detailed chromosomal research that shows altered chromosomal content, can be used to aid in diagnosis. A blood sample can be used to extract chromosomes. The chromosomes used in this test are colored to make them easier to see, and after being looked at under a microscope, the altered chromosomes can be seen (karyotyping).

A more sensitive test called fluorescent in situ hybridization (FISH) might be required to pinpoint the exact breakpoint or search for a putative deletion missed by G−band analysis. In a FISH examination, probes tagged with a particular fluorescent dye are affixed to a particular chromosome, enabling researchers to see that particular section of the chromosome. Newer methods replace such techniques as an initial line of defense. Array comparative genome hybridization is one of them (array CGH).


ATR−16 syndrome is treated according to the distinct symptoms present in each patient. The concerted action of a group of professionals may be necessary throughout treatment. It may be necessary for pediatricians, neurologists, hematologists, and other medical specialists to arrange a child's treatment carefully and thoroughly. Additionally important is the need for family−wide psychosocial support.

Early intervention services ensure that afflicted children attain their full potential throughout childhood and toddlerhood (well before age three). Speech therapy, special remedial education, and other medical and social assistance are special services that may benefit kids. For infants and toddlers with disabilities, an Individualized Family Support Plan (IFSP) may be created to direct the early intervention process. If special services are required for a child's education, an individual education plan (IEP) may be created. Due to the wide range in the severity of an intellectual disability, such planning is customized.

Affected Populations

Male and female patients with ATR−16 syndrome are both affected equally. The true prevalence in the regular populace can be difficult to ascertain because cases might go untreated or get the wrong diagnosis.


While some new−borns exhibit is distinguishing facial characteristics, such as hypertelorism, a nose with a broad, prominent bridge, small ears, and a short neck; they do not need to have ATR−16 Syndrome, but it is not wise to dismiss it either without properly studying it. It is a rare disease and extremely prevalent. However, it also is because it is largely undiscovered.