Abruzzo–Erickson syndrome is an extremely rare disorder characterized by

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

, protruding ears,

coloboma A coloboma (from the Greek , meaning defect) is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is pres ...

, a

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...

or palatal rugosity, radial synostosis, and short stature. It was first characterized by Abruzzo and Erickson in 1977 as a CHARGE like syndrome as variably expressed among a family of two brothers, their mother, and their maternal uncle. Members of this family exhibited many of the CHARGE symptoms, but notably did not have choanal atresia and the brothers experienced typical genital development. Due to the recent discovery of this disorder, its etiology is not fully known but it is understood that it arises from mutations on the

TBX22 T-box transcription factor TBX22 is a protein that in humans is encoded by the ''TBX22'' gene. TBX22 is a member of a phylogenetically conserved family of proteins that share a common DNA-binding domain, the T-box. T-box genes encode transcriptio ...

gene on the X-chromosome. The disorder is inherited in an

X-linked recessive X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y ...

manner. There is currently no known cure but its symptoms can be treated.

Signs and Symptoms

Abruzzo-Erikson syndrome is characterized by

hypospadias Hypospadias is a common variation in fetal development of the penis in which the urethra does not open from its usual location in the head of the penis. It is the second-most common birth abnormality of the male reproductive system, affecting abou ...

, deafness, short stature, and radial synostosis. There are also additional symptoms that are very similar to

CHARGE syndrome CHARGE syndrome (formerly known as CHARGE association) is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart ...

such as large and protruding ears, wide spacing between the second and third fingers,

ulnar deviation Ulnar deviation, also known as ulnar drift, is a hand deformity in which the swelling of the metacarpophalangeal joints (the big knuckles at the base of the fingers) causes the fingers to become displaced, tending towards the little finger. Its na ...

, facial asymmetry, dental abnormalities, and congenital heart malformation. However, in contrast to

, patients with Abruzzo-Erikson syndrome do not display intellectual disability,

choanal atresia Choanal atresia is a congenital disorder where the back of the nasal passage (choana) is blocked, usually by abnormal bony or soft tissue (membranous) due to failed hole development of the nasal fossae during prenatal development. It causes persi ...

, or genital hypoplasia. As with most diseases, the symptoms will vary from person to person.

Genetics

While the complete etiology is not fully known, Abruzzo-Erickson Syndrome arises in part due to mutations on the TBX22

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

, a gene that is located on the X-chromosome (around 80,014,753 to 80,031,774 bp), and is inherited in an X-linked recessive manner. The T-box transcription factor TBX22 plays an essential role in normal craniofacial development.

Nonsense Nonsense is a communication, via speech, writing, or any other symbolic system, that lacks any coherent meaning. Sometimes in ordinary usage, nonsense is synonymous with absurdity or the ridiculous To be ridiculous is to be something which is ...

frameshift Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can ...

, splice-site and

missense In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense mu ...

mutations in this region can result in patients with X-linked cleft palate (CPX) and

ankyloglossia Ankyloglossia, also known as tongue-tie, is a congenital oral anomaly that may decrease the mobility of the tongue tip and is caused by an unusually short, thick lingual frenulum, a membrane connecting the underside of the tongue to the floor of ...

phenotypes. The CPX phenotype observed in individuals with Abruzzo-Erickson Syndrome most likely results from a loss of protein function as severely truncated proteins can result from the introduction of a premature stop codon can result from nonsense, splice-site, or frame shift sequence changes, while missense mutations in this region have less of a structural effect on the protein, but instead interferes with DNA binding and transcriptional activity.

Diagnosis

Abruzzo–Erickson syndrome can be diagnosed on the basis of a complete physical examination (as patients with the syndrome often possess noticeable physical characteristics such as a

, large protruding ears, and facial asymmetry). As the syndrome is inherited, a complete medical history is also taken, and additional assessments may be made based on the results of laboratory tests,

biopsies A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

, and imaging studies. Genetic and molecular tests such as DNA sequencing can also be used for a complete diagnosis of Abruzzo–Erickson syndrome.

Treatment

There is no cure for this condition. However, children with Abruzzo-Erikson syndrome can survive into adulthood and live productive lives as long as they are treated from an early age. Many life-threatening problems may arise in these children which need to be addressed. Treatment is generally focused on addressing the specific symptoms and not the syndrome itself. Since hearing problems are common with this syndrome, it is usually the first issue addressed. Correction of some abnormalities can be corrected with the use of extensive multidisciplinary

craniofacial surgery Craniofacial surgery is a surgical subspecialty that deals with congenital disorder, congenital and acquired deformity, deformities of the human head, head, human skull, skull, face, neck, jaws and associated structures. Although craniofacial treat ...

. Physical therapy and occupational therapy are important to ensure they can live a normal and productive life. Monitoring the heart for defects is also common and there are medications to educe this risk or surgery is available to correct some of conditions.

Epidemiology

Abruzzo-Erickson Syndrome is an extremely rare condition, prevalent among less than one in a million of individuals. As of 2021, only four cases have been characterized in literature.

References

External links

* {{DEFAULTSORT:Abruzzo-Erickson syndrome Syndromes affecting stature Genetic disorders with OMIM but no gene Syndromes affecting hearing Diseases named for discoverer