XK aprosencephaly (also called Garcia-Lurie syndrome, aprosencephaly, and aprosencephaly-atelencephaly syndrome) is an extremely rare
congenital disorder
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
characterized by the absence of the embryonic
forebrain
In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the Anatomical terms of location#Directional terms, rostral (forward-most) portion of the brain. The forebrain (prosencephalon), the midbrain (mesencephalon), and hin ...
. Because the prosencephalon gives way to the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
, survival with aprosencephaly is not possible outside utero. The external symptoms are similar to
holoprosencephaly
Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres, typically occurring between the 18th and 28th day of gestation. Normally, the forebrain is formed and t ...
, a related disorder, including a smaller than normal head (
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
), small eyeballs (
microphthalmia
Microphthalmia (Greek: grc, μικρός, mikros, small, label=none, grc, ὀφθαλμός, ophthalmos, eye, label=none, also referred as microphthalmos, is a developmental disorder of the eye in which one (unilateral microphthalmia) or both ( ...
), a small mouth (
microstomia),
anal atresia
An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unkno ...
(no anus), and abnormalities of the external genitalia,
radius
In classical geometry, a radius ( : radii) of a circle or sphere is any of the line segments from its center to its perimeter, and in more modern usage, it is also their length. The name comes from the latin ''radius'', meaning ray but also the ...
,
nostril
A nostril (or naris , plural ''nares'' ) is either of the two orifices of the nose. They enable the entry and exit of air and other gasses through the nasal cavities. In birds and mammals, they contain branched bones or cartilages called turbi ...
s, and
pharynx
The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struc ...
(throat).
Presentation
There are many different symptoms that may indicate the presence of aprosencephaly. Patients typically have a smaller than normal skull, eyes, and mouth, termed microcephaly, microphthalmia, and microstomia. The eyes themselves may be closely separated (
hypotelorism
Hypotelorism is an abnormally decreased distance between two organs or bodily parts, usually pertaining to the eye sockets (orbits), also known as orbital hypotelorism.
Causes
It is often a result of fetal alcohol syndrome (FAS), caused by lar ...
) or fused (
cyclopia
Cyclopia (named after the Greek mythology character cyclopes) is the most extreme form of holoprosencephaly and is a congenital disorder (birth defect) characterized by the failure of the embryonic prosencephalon to properly divide the orbits of ...
).
Infants affected by aprosencephaly often have a variety of abnormalities in the bones of the forearm, hand, and foot (called pre-axial limb defects), including small or absent thumbs, small or absent
big toe
Toes are the digits (fingers) of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being ''digitigrade''. Humans, and other animals that walk on the soles of their feet, are described as being ''plant ...
, small hands, and various malformations of the radius (the main bone in the forearm).
Other associated symptoms include anal atresia, in which an infant is born without an anus, atrial septal defect (a hole between the top two chambers of the heart), ventricular septal defect (a hole between the bottom two chambers of the heart), and ambiguous genitalia.
During pregnancy, too much amniotic fluid may be present, a condition called polyhydramnios.
Causes
No single cause is responsible for aprosencephaly. In 2005, it was found that
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
mutations of the
SIX3
Homeobox protein SIX3 is a protein that in humans is encoded by the ''SIX3'' gene.
Function
The SIX homeobox 3 (SIX3) gene is crucial in embryonic development by providing necessary instructions for the formation of the forebrain and eye deve ...
gene located on the short arm of
chromosome 2
Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...
could result in aprosencephaly. Some cases were linked to
trisomy 13
A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes).
Description and causes
Most organisms that reprodu ...
, a disorder which also has a correlation with holoprosencephaly.
Diagnosis
The diagnosis of aprosencephaly is made clinically with the use of skeletal imaging, brain imaging, and
autopsy
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...
.
Almost all fetuses with aprosencephaly naturally
miscarry
Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is fetal viability, able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE a ...
before the third trimester.
History
A case of XK aprosencephaly was first reported in 1977, and was proposed as a genetic syndrome in 1988. As of 2015, less than 10 cases of aprosencephaly are reported in the medical literature.
Terminology
Aprosencephaly is named so by combining the
Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
prefix a- (without, lacking) and -prosencephalon (the embryonic forebrain). The syndromic form is known as XK aprosencephaly, with 'X' and 'K' referring to the surnames of the first two patients described with aprosencephaly.
[{{Cite web, title=OMIM Entry – 207770 – APROSENCEPHALY SYNDROME, url=https://omim.org/entry/207770, website=]Online Mendelian Inheritance in Man
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM r ...
, access-date=2019-06-05
References
Rare diseases
Genetic diseases and disorders