Iniencephaly is a rare type of

cephalic disorder Cephalic disorders () are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. Cephalic disorders are not necessarily caused by a single factor, but may be influenced by hereditary or genetic ...

characterised by three common characteristics: a defect to the

occipital bone The occipital bone () is a neurocranium, cranial dermal bone and the main bone of the occiput (back and lower part of the skull). It is trapezoidal in shape and curved on itself like a shallow dish. The occipital bone overlies the occipital lobe ...

spina bifida Spina bifida (Latin for 'split spine'; SB) is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, me ...

of the

cervical vertebrae In tetrapods, cervical vertebrae (singular: vertebra) are the vertebrae of the neck, immediately below the skull. Truncal vertebrae (divided into thoracic and lumbar vertebrae in mammals) lie caudal (toward the tail) of cervical vertebrae. In ...

and retroflexion (backward bending) of the head on the

cervical spine In tetrapods, cervical vertebrae (singular: vertebra) are the vertebrae of the neck, immediately below the skull. Truncal vertebrae (divided into thoracic and lumbar vertebrae in mammals) lie caudal (toward the tail) of cervical vertebrae. In sau ...

Stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...

is the most common outcome, with a few rare examples of live birth, after which death invariably occurs within a short time. The disorder was first described by

Étienne Geoffroy Saint-Hilaire Étienne Geoffroy Saint-Hilaire (15 April 177219 June 1844) was a French naturalist who established the principle of "unity of composition". He was a colleague of Jean-Baptiste Lamarck and expanded and defended Lamarck's evolutionary theories. ...

in 1836. The name is derived from the

Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Dark Ages (), the Archaic peri ...

word ἰνίον ''inion'', for the occipital bone/nape of the neck.

Classifications

There are two types of iniencephaly. The more severe group is iniencephaly apertus (open iniencephaly), involving the development of an

encephalocele Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal develop ...

. In the other group, iniencephaly clausus (closed iniencephaly), the encephalocele is absent.

Signs and symptoms

The affected infant tends to be short, with a disproportionately large head. The fetal head of infants born with iniencephaly are hyperextended while the

foramen magnum The foramen magnum ( la, great hole) is a large, oval-shaped opening in the occipital bone of the skull. It is one of the several oval or circular openings (foramina) in the base of the skull. The spinal cord, an extension of the medulla oblon ...

is enlarged and opens through the widened pedicles. The defective neural arches directly into the upper cervical reach of the

spinal canal The spinal canal (or vertebral canal or spinal cavity) is the canal that contains the spinal cord within the vertebral column. The spinal canal is formed by the vertebrae through which the spinal cord passes. It is a process of the dorsal body ca ...

, causing the formation of a common cavity between most of the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

and the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

. The skin of the anterior chest is connected directly to the face, bypassing the formation of a neck, while the scalp is directly connected to the skin of the back. Because of this, those born with this anomaly either have a highly shortened neck or no neck at all. This causes extreme retroflexion, or backward bending, of the head in a "star-gazing" fashion. The spine is severely distorted as well along with significant shortening due to marked

lordosis Lordosis is historically defined as an ''abnormal'' inward curvature of the lumbar spine. However, the terms ''lordosis'' and ''lordotic'' are also used to refer to the normal inward curvature of the lumbar and cervical regions of the human spi ...

. The vertebrae, especially cervical, are fused together in abnormal shapes and their numbers are reduced. The spinal cord is almost always defective while the

ventricular system The ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventricular system is con ...

is often dilated and the

cortex Cortex or cortical may refer to: Biology * Cortex (anatomy), the outermost layer of an organ ** Cerebral cortex, the outer layer of the vertebrate cerebrum, part of which is the ''forebrain'' *** Motor cortex, the regions of the cerebral cortex i ...

is thinned. Sometimes, in the case of iniencephaly apertus, an

(sac-like protrusions of the brain through an opening in the cranium) forms.

Additional symptoms

Additional symptoms include:

Causes

Though the iniencephaly is not genetic with its cause unknown, studies have shown that there are certain factors that can increase the risk of mothers giving birth to children with these anomalies.

Chromosomal abnormalities

Abnormalities in chromosomes such as

trisomy 18 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 ...

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 ...

, and monosomy X have been shown to be tied to this disorder.

Environmental factors

Mothers with poor socioeconomic conditions, poor nutrition, low parity, and lack of folic acid supplementation, and/or

hyperhomocysteinemia Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood, conventionally described as above 15 μmol/L. As a consequence of the biochemical reactions in which homocysteine is involved ...

have shown to be at larger risk.

Drugs

Animal studies have shown that administration of the drugs

vinblastine Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder ca ...

, streptonigrin, triparano,

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...

tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...

antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...

, and antitumor agents to pregnant mothers have resulted in offspring born with iniencephaly. The drug

clomiphene Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. Use results in a greater chance of twins. It is taken by mouth once a day, with a course ...

, a drug commonly used for ovulation stimulation in fertility treatments, has also been seen to be associated with iniencephaly.

Obesity

Studies have shown that obesity of the mother increases the risk of neural tube disorders such as iniencephaly by 1.7 fold while severe obesity increases the risk by over 3 fold.

History of iniencephaly

Once a mother has given birth to a child with iniencephaly, risk of reoccurrence increases to 1-5%.

Pathogenesis

The exact

pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

of iniencephaly is still unknown though there are proposed theories, most of which view the neural tube malformation from the primary neural anomaly standpoint. Marin-Padilla and MarinPadilla have proposed that the cause for the abnormalities has to do with a deficiency in the primary

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

. P. Erdinçler, et al. suggests from their findings that the cause of the anomaly is actually a defect in the

and

rachischisis Rachischisis (Greek language, Greek: "rhachis - ῥάχις" - spine, and "schisis - σχίσις" - split) is a developmental birth defect involving the neural tube. This anomaly occurs in utero, when the posterior neuropore of the neural tube f ...

of the posterior vertebral arches leading to

herniation A hernia is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. Various types of hernias can occur, most commonly involving the abdomen, and specifically the groin. Groin herni ...

of neural tissue through the opening in the bone during

gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pregna ...

Diagnosis

The most accurate method of diagnosis is prenatal screening through real-time fetal images. However, since maternal body habitus leads to diagnostic difficulties using this method,

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

and

sonography Medical ultrasound includes diagnostic techniques (mainly medical imaging, imaging techniques) using ultrasound, as well as therapeutic ultrasound, therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal ...

are the most commonly used technique since there is no exposure to

ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...

. At the beginning of the second trimester, the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

(CNS) and anatomic structures of the fetus can be clearly visualized and the characteristic malformations of iniencephaly, such as a shortened trunk, marked

in the cervicothoracic vertebrae, absence or partial absence of the occipital squama, abnormal fusion of vertebrae, closed

vertebral arches The vertebral column, also known as the backbone or spine, is part of the axial skeleton. The vertebral column is the defining characteristic of a vertebrate in which the notochord (a flexible rod of uniform composition) found in all chordate ...

, formation of an

(for iniencephaly apertus), and

dorsiflexion Motion, the process of movement, is described using specific anatomical terms. Motion includes movement of organs, joints, limbs, and specific sections of the body. The terminology used describes this motion according to its direction relative ...

of the head in respect to the spine, can be precisely diagnosed as well as the severity and location established. Once established, further decisions can be made with regard to terminating the pregnancy or providing a plan of adequate postnatal care.

Differential diagnosis

Since many of the characteristics of iniencephaly, such as

congenital 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 ...

retroflexion A retroflex ( /ˈɹɛtʃɹoːflɛks/), apico-domal ( /əpɪkoːˈdɔmɪnəl/), or cacuminal () consonant is a coronal consonant where the tongue has a flat, concave, or even curled shape, and is articulated between the alveolar ridge and the har ...

of the spine and fusion of the cervical vertebrae, are shared with other disorders, key differences are important to note. While

anencephaly Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fai ...

experiences a partial to total lack of the

neurocranium In human anatomy, the neurocranium, also known as the braincase, brainpan, or brain-pan is the upper and back part of the skull, which forms a protective case around the brain. In the human skull, the neurocranium includes the calvaria (skull), ...

, iniencephaly does not. In anencephaly, the retroflexed head is not covered with skin while in iniencephaly, the retroflexed head is covered with skin entirely. Cervical vertebrae are malformed and reduced in iniencephaly while they are almost normal in anencephaly. Even though KFS does experience malformed cervical vertebra due to failure of segmentation during early fetal development, there is not retroflexion of the head as seen in iniencephaly. While iniencephaly clausus is fatal, KFS is not and can be surgically corrected. Therefore, it is crucial to correctly diagnose KFS and not mistake it for iniencephaly clausus.

Prevention

Pregnant mothers are advised to take

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

supplements to reduce risk of iniencephaly by up to 70%. Pregnant mothers are also advised not to take

antiepileptic drugs Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...

, and sulfa drugs, all of which have been associated with increased risk for neural tube defects."NINDS Iniencephaly Information Page."
National Institute of Neurological Disorders and Stroke (NINDS). NINDS, 13 Feb. 2007. Web. 30 Nov. 2012.

Treatment

Since newborns with iniencephaly so rarely survive past childbirth, a standard treatment does not exist.

Prognosis

Iniencephaly of both types carry a lethal prognosis, sometimes even ending in

spontaneous abortion Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...

stillborns Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term i ...

. Most infants die within hours of childbirth. There are only seven reported cases of relatively long-term survival of those born with iniencephaly.

Epidemiology

Iniencephaly is thought to make up around 1% of all fetal abnormalities, with an incidence rate estimated at 0.1 to 10 in 10,000 deliveries. For unknown reasons, this disease seems to occur most often in newborn females (about 90%).

References

External links

{{Congenital malformations and deformations of nervous system Congenital disorders of nervous system Rare diseases