Johanson-Blizzard syndrome
Encyclopedia
Johanson–Blizzard syndrome (JBS) is a rare, sometimes fatal autosomal
recessive multisystem congenital disorder
featuring abnormal development of the pancreas
, nose
and scalp
, with mental retardation
, hearing loss and growth failure. It is sometimes described as a form of ectodermal dysplasia
.
The disorder is especially noted for causing profound developmental errors and exocrine dysfunction of the pancreas, and it is considered to be an inherited pancreatic disease.
exocrine insufficiency
. Varying degrees of decreased secretion
of lipase
s, pancreatic juice
s such as trypsin
, trypsinogen
and others, as well as malabsorption
of fat
s and disruptions of glucagon
secretion and its response to hypoglycemia
caused by insulin
activity are major concerns when JBS is diagnosed. Associated with developmental errors, impaired apoptosis
, and both prenatal and chronic inflammatory
damage, necrosis
and fibrosis
of the pancreatic acini
(clusters of pancreatic exocrine gland
tissue, where secretion of pancreatic juice and related enzyme
s occurs), pancreatic exocrine insufficiency in JBS can additionally stem from congenital replacement of the acini with fatty tissue
. Near total replacement of the entire pancreas with fatty tissue has also been reported. This is a progressive, sometimes fatal consequence of the disorder.
are ducts in the pancreas where endocrine activity such as the release of hormone
s glucagon, somatostatin
and insulin takes place. Pancreatic endocrine insufficiency in JBS can be associated with either a buildup of connective tissue
in the islet regions, congenital replacement of the islets with fatty tissue, or improper nerve
signalling to the islets. Endocrine dysfunction of the pancreas often results in diabetes mellitus
. Both insulin resistance
and diabetes have been observed with JBS, and it is suggested that diabetes should be considered as a complication of JBS and its course.
Ductular output of fluids and electrolyte
s is preserved in the pancreas of many with JBS, as well as moderate to normal levels of functioning bicarbonate
.
Endocrine abnormalities in other areas have also been present with the disorder. These include hypothyroidism
, growth hormone deficiency
and hypopituitarism
. Findings affecting pituitary function in some JBS patients have included such anomalies as the formation of a glial hamartoma
(a neoplasm, or tumor
composed of glial cell
s) on a lobe of the pituitary gland
, as well congenital underdevelopment of the anterior pituitary
. Growth failure and associated short stature
(dwarfism
) in JBS can be attributed to growth hormone deficiency caused by diminished anterior pituitary function, with malabsorption of fats playing a subsequent role.
(underdevelopment) of the nasal alae, or "wing of the nose
". Both hypoplasia and aplasia
(partial or complete absence) of structural cartilage
and tissue
in this area of the nose, along with the underlying alae nasi muscle
, are prevailing features of the disorder. Together, these malformations give the nose and nostril
s an odd shape and appearance.
. Normal intelligence and age appropriate social development, however, have been reported in a few instances of JBS.
in JBS give explanation to the presence of bilateral sensorineural hearing loss
in most patients affected by the disorder. The formation of cyst
ic tissue in both the cochlea
and vestibule
, with resulting dilation
(widening) and malformation of these delicate structures has been implicated. Congenital deformations of the temporal bone
and associated adverse anatomical effects on innervation and development of the inner ear also contribute to this type of hearing loss.
, face
, jaw
and teeth may be found with JBS. These include: ectoderm
al mid-line scalp defects with sparse, oddly-patterned hair
growth; aplasia cutis (underdeveloped, very thin skin
) over the head, an enlarged fontanelle
("soft spot" on the head of young infant
s), microcephaly
(undersized skull
), prominent forehead
, absence of eyebrow
s and eyelash
es, mongoloidal
eye
shape, nasolacrimo-
cutaneous fistula
e (this refers to the formation of an abnormal secondary passageway from either the tear duct or lacrimal sac
to the facial skin surface, possibly discharging fluid), flattened ear
s, micrognathism
of the maxilla
and mandible (underdevelopment of the upper and lower jaw, respectively), with the maxilla more prominently affected in some cases; congenital clefting of bone
s surrounding the optical orbit
(eye socket), such as the frontal
and lacrimal bone
; and maldeveloped deciduous teeth
("baby teeth"), with an absence of permanent teeth
.
, and less common features of JBS have included: imperforate anus
(occlusion of the anus
), vesicoureteral reflux
(reversal of the flow of urine
, from the bladder
back into the ureter
s, toward the kidney
s); duplex of the uterus
and vagina
in female
infants, neonatal cholestasis
of the liver
, with cirrhosis
and portal hypertension
(high blood pressure
in the hepatic portal vein
); dilated cardiomyopathy
, dextrocardia
(congenital displacement of the heart
to the right side of the chest
), atrial
and ventricular septal defect
; low birth-weight
, failure to thrive
, hypotonia
(decreased muscle tone
); sacral hiatus
(a structural deficiency of the sacral vertebrae
), congenital cataracts
, and cafe-au-lait spots.
s in the UBR1
gene, which encodes one of several ubiquitin ligase
enzymes of the N-end rule pathway.
The protein ubiquitin
is a universal, "ubiquitously" expressed protein common to eukaryotic
organism
s. Ubiquitin plays a role in the regulation
of other proteins by tagging them for eventual degradation by proteasome
s. This process begins when ubiquitin ligase covalently
attaches a ubiquitin molecule
to the lysine
side chain
of the target protein substrate
(the misfolded, damaged, malfunctioning or unneeded protein that needs to be degraded). This is repeated a number of times in succession forming a chain of ubiquitin molecules, which is a process referred to as polyubiquitination. The polyubiquitination of the target protein signals the proteasome to break it down, which it does via proteolysis
. The ubiquitin-proteasome system plays a crucial role in the non-lysosomal
degradation of intracellular proteins, and ubiquitin can also participate in modifying
proteins to perform certain tasks. Both degradation and modification of proteins within the cell are part of a broader regulatory scheme, necessary for cellular processes such as cell division
, cell signalling, cell surface receptor
function, apoptosis
, DNA
maintenance, inflammatory response and developmental quality control associated with the cell cycle
and homeostasis
in general.
Ubiquitin-mediated degradation of proteins occurs through the N-end rule
pathway. In eukaryotes, including humans, the N-end rule pathway is part of the ubiquitin system. Composed of a highly-selective single-residue
code (a single amino acid
nucleotide
sequence), the N-end rule serves as a mechanism which can relate the stability of a protein to the identity of the amino acid at its N-terminus (the end of the polypeptide with an amino group, which in the ubiquitin system may be involved in the reactive destabilization of the protein).
In JBS, mutations in the UBR1 gene alter, disrupt or prevent the synthesis of ubiquitin ligase. In the pancreatic acinar cells, UBR1 is more highly expressed than anywhere else in the body. Impairment of the ubiquitin-proteasome system directly related to insufficient activity of ubiquitin ligase has been established as the cause of both congenital and progressive inflammatory damage, fatty tissue replacement, connective tissue proliferation and errors in innervation of the acini and islets, correlating to failures of normal apoptotic destruction of damaged cells and constitutive malpresence of proteins. This also applies to other areas affected by deleterious UBR1 expression, such as the craniofacial area, musculoskeletal and nervous systems, dentition and organs.
Missense
, nonsense
and splice site mutation
s of the UBR1 gene in both parents have been found with JBS, confirming the homozygous nature of the JBS phenotype
. Variability of the phenotype, associated with residual ubiquitin ligase activity in some patients, has also been attributed to hypomorphic mutations occasionally found in either of the carrier parents. The UBR1 gene is located on human chromosome
15.
Pancreatic insufficiency and malabsorption can be managed with pancreatic enzyme replacement therapy, such as pancrelipase
supplementation and other related methods.
Craniofacial and skeletal deformities may require surgical correction, using techniques including bone grafts and osteotomy
procedures. Sensorineural hearing loss can be managed with the use of hearing aid
s and educational services designated for the hearing impaired.
Special education, specialized counseling methods and occupational therapy
designed for those with mental retardation have proven to be effective, for both the patient and their families. This, too, is carefully considered for JBS patients.
JBS is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome
, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
, who first described the disorder in a 1971 journal report.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive multisystem congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
featuring abnormal development of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
, nose
Human nose
The visible part of the human nose is the protruding part of the face that bears the nostrils. The shape of the nose is determined by the ethmoid bone and the nasal septum, which consists mostly of cartilage and which separates the nostrils...
and scalp
Scalp
The scalp is the anatomical area bordered by the face anteriorly and the neck to the sides and posteriorly.-Layers:It is usually described as having five layers, which can conveniently be remembered as a mnemonic:...
, with mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, hearing loss and growth failure. It is sometimes described as a form of ectodermal dysplasia
Ectodermal dysplasia
Ectodermal dysplasia is not a single disorder, but a group of syndromes all deriving from abnormalities of the ectodermal structures. More than 150 different syndromes have been identified. Despite some of the syndromes having different genetic causes the symptoms are sometimes very similar...
.
The disorder is especially noted for causing profound developmental errors and exocrine dysfunction of the pancreas, and it is considered to be an inherited pancreatic disease.
Exocrine
The most prominent effect of JBS is pancreaticExocrine pancreas
The exocrine pancreas has ducts that are arranged in clusters called acini . Pancreatic secretions are secreted into the lumen of the acinus, and then accumulate in intralobular ducts that drain to the main pancreatic duct, which drains directly into the duodenum.Control of the exocrine function of...
exocrine insufficiency
Exocrine pancreatic insufficiency
Exocrine pancreatic insufficiency is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. This disease is found frequently in dogs. EPI is also found in humans afflicted with cystic fibrosis and Shwachman-Diamond Syndrome. EPI is caused by a progressive...
. Varying degrees of decreased secretion
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
of lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
s, pancreatic juice
Pancreatic juice
Pancreatic juice is a liquid secreted by the pancreas, which contains a variety of enzymes, including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase, and amylase....
s such as trypsin
Trypsin
Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...
, trypsinogen
Trypsinogen
Trypsinogen is the precursor form or zymogen of the pancreatic enzyme trypsin. It is found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is activated by enteropeptidase, which is found in the intestinal mucosa, to form trypsin. Once activated, the trypsin can activate...
and others, as well as malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
of fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
s and disruptions of glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
secretion and its response to hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
caused by insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
activity are major concerns when JBS is diagnosed. Associated with developmental errors, impaired apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, and both prenatal and chronic inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
damage, necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
and fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
of the pancreatic acini
Acinus
An acinus refers to any cluster of cells that resembles a many-lobed "berry," such as a raspberry...
(clusters of pancreatic exocrine gland
Exocrine gland
Exocrine glands are a type of ductal glands that secrete their products into ducts that lead directly into the external environment...
tissue, where secretion of pancreatic juice and related enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s occurs), pancreatic exocrine insufficiency in JBS can additionally stem from congenital replacement of the acini with fatty tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
. Near total replacement of the entire pancreas with fatty tissue has also been reported. This is a progressive, sometimes fatal consequence of the disorder.
Endocrine
Endocrine insufficiency of the pancreas occurs with JBS, though it is sometimes less common and less pronounced than the more prominent effects on exocrine function. The islets of LangerhansIslets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
are ducts in the pancreas where endocrine activity such as the release of hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s glucagon, somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
and insulin takes place. Pancreatic endocrine insufficiency in JBS can be associated with either a buildup of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
in the islet regions, congenital replacement of the islets with fatty tissue, or improper nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
signalling to the islets. Endocrine dysfunction of the pancreas often results in diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. Both insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
and diabetes have been observed with JBS, and it is suggested that diabetes should be considered as a complication of JBS and its course.
Ductular output of fluids and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
s is preserved in the pancreas of many with JBS, as well as moderate to normal levels of functioning bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
.
Endocrine abnormalities in other areas have also been present with the disorder. These include hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, growth hormone deficiency
Growth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
and hypopituitarism
Hypopituitarism
Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...
. Findings affecting pituitary function in some JBS patients have included such anomalies as the formation of a glial hamartoma
Hamartoma
A hamartoma is a benign, focal malformation that resembles a neoplasm in the tissue of its origin. This is not a malignant tumor, and it grows at the same rate as the surrounding tissues. It is composed of tissue elements normally found at that site, but which are growing in a disorganized mass...
(a neoplasm, or tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
composed of glial cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s) on a lobe of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, as well congenital underdevelopment of the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
. Growth failure and associated short stature
Short stature
Short stature refers to a height of a human being which is below expected. Shortness is a vague term without a precise definition and with significant relativity to context...
(dwarfism
Dwarfism
Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....
) in JBS can be attributed to growth hormone deficiency caused by diminished anterior pituitary function, with malabsorption of fats playing a subsequent role.
Nasal
The primary malformation apparent with JBS is hypoplasiaHypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
(underdevelopment) of the nasal alae, or "wing of the nose
Wing of the nose
The wing or ala of the nose is the lateral surface of the external nose that flares out to form a rounded eminence around the nostril. It is elevated by the levator labii superioris alaeque nasi muscle and receives sensory innervation by the maxillary division of the Trigeminal Nerve ....
". Both hypoplasia and aplasia
Aplasia
Aplasia is defined in general as "defective development or congenital absence of an organ or tissue." In the field of hematology, the term refers to "incomplete, retarded, or defective development, or cessation of the usual regenerative process."-Examples:*Acquired pure red cell aplasia*Aplasia...
(partial or complete absence) of structural cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
in this area of the nose, along with the underlying alae nasi muscle
Depressor septi nasi muscle
The depressor septi arises from the incisive fossa of the maxilla.Its fibers ascend to be inserted into the nasal septum and back part of the alar part of nasalis muscle....
, are prevailing features of the disorder. Together, these malformations give the nose and nostril
Nostril
A nostril is one of the two channels of the nose, from the point where they bifurcate to the external opening. In birds and mammals, they contain branched bones or cartilages called turbinates, whose function is to warm air on inhalation and remove moisture on exhalation...
s an odd shape and appearance.
Neurological
Mental retardation ranging from mild to severe is present in the majority of JBS patients, and is related to the deleterious nature of the known mutagen responsible for the disorder and its effects on the developing central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. Normal intelligence and age appropriate social development, however, have been reported in a few instances of JBS.
Auditory
Findings with the inner earInner ear
The inner ear is the innermost part of the vertebrate ear. In mammals, it consists of the bony labyrinth, a hollow cavity in the temporal bone of the skull with a system of passages comprising two main functional parts:...
in JBS give explanation to the presence of bilateral sensorineural hearing loss
Sensorineural hearing loss
Sensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
in most patients affected by the disorder. The formation of cyst
Cyst
A cyst is a closed sac, having a distinct membrane and division on the nearby tissue. It may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst could go away on its own or may have to be removed through surgery.- Locations :* Acne...
ic tissue in both the cochlea
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
and vestibule
Vestibule of the ear
-Definition:The vestibule is the central part of the osseous labyrinth, and is situated medial to the tympanic cavity, behind the cochlea, and in front of the semicircular canals.The etymology comes from the Latin vestibulum, literally an entrance hall....
, with resulting dilation
Dilation
Dilation refers to an enlargement or expansion in bulk or extent, the opposite of contraction. It derives from the Latin dilatare, "to spread wide".In physiology:* Pupillary dilation, dilation of the pupil of the eye...
(widening) and malformation of these delicate structures has been implicated. Congenital deformations of the temporal bone
Temporal bone
The temporal bones are situated at the sides and base of the skull, and lateral to the temporal lobes of the cerebrum.The temporal bone supports that part of the face known as the temple.-Parts:The temporal bone consists of four parts:* Squama temporalis...
and associated adverse anatomical effects on innervation and development of the inner ear also contribute to this type of hearing loss.
Craniofacial
Other abnormalities, affecting the scalp, headHead
In anatomy, the head of an animal is the rostral part that usually comprises the brain, eyes, ears, nose and mouth . Some very simple animals may not have a head, but many bilaterally symmetric forms do....
, face
Face
The face is a central sense organ complex, for those animals that have one, normally on the ventral surface of the head, and can, depending on the definition in the human case, include the hair, forehead, eyebrow, eyelashes, eyes, nose, ears, cheeks, mouth, lips, philtrum, temple, teeth, skin, and...
, jaw
Jaw
The jaw is any opposable articulated structure at the entrance of the mouth, typically used for grasping and manipulating food. The term jaws is also broadly applied to the whole of the structures constituting the vault of the mouth and serving to open and close it and is part of the body plan of...
and teeth may be found with JBS. These include: ectoderm
Ectoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...
al mid-line scalp defects with sparse, oddly-patterned hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
growth; aplasia cutis (underdeveloped, very thin skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
) over the head, an enlarged fontanelle
Fontanelle
A fontanelle is an anatomical feature on an infant's skull.-Anatomy:Fontanelles are soft spots on a baby's head which, during birth, enable the bony plates of the skull to flex, allowing the child's head to pass through the birth canal. The ossification of the bones of the skull causes the...
("soft spot" on the head of young infant
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
s), microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
(undersized skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...
), prominent forehead
Forehead
For the Arsenal striker see GervinhoIn human anatomy, the forehead is the fore part of the head. It is, formally, an area of the head bounded by three features, two of the skull and one of the scalp. The top of the forehead is marked by the hairline, the edge of the area where hair on the scalp...
, absence of eyebrow
Eyebrow
The eyebrow is an area of thick, delicate hairs above the eye that follows the shape of the lower margin of the brow ridges of some mammals. Their main function is to prevent sweat, water, and other debris from falling down into the eye socket, but they are also important to human communication and...
s and eyelash
Eyelash
An eyelash or simply lash is one of the hairs that grow at the edge of the eyelid. Eyelashes protect the eye from debris and perform some of the same function as whiskers do on a cat or a mouse in the sense that they are sensitive to being touched, thus providing a warning that an object is near...
es, mongoloidal
Mongoloid race
Mongoloid is a term sometimes used by forensic anthropologists and physical anthropologists to refer to populations that share certain phenotypic traits such as epicanthic fold and shovel-shaped incisors and other physical traits common in East Asia, the Americas and the Arctic...
eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
shape, nasolacrimo-
Nasolacrimal duct
The nasolacrimal duct carries tears from the lacrimal sac into the nasal cavity. Excess tears flow through nasolacrimal duct which drains into the inferior nasal meatus...
cutaneous fistula
Fistula
In medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Locations:Fistulas can develop in various parts of the...
e (this refers to the formation of an abnormal secondary passageway from either the tear duct or lacrimal sac
Lacrimal sac
The lacrimal sac is the upper dilated end of the nasolacrimal duct, and is lodged in a deep groove formed by the lacrimal bone and frontal process of the maxilla...
to the facial skin surface, possibly discharging fluid), flattened ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
s, micrognathism
Micrognathism
Micrognathism is a condition where the jaw is undersized. It is also sometimes called "Mandibular hypoplasia". It is common in infants, but is usually self-corrected during growth, due to the jaws increasing in size. It may be a cause of abnormal tooth alignment and in severe cases can hamper...
of the maxilla
Maxilla
The maxilla is a fusion of two bones along the palatal fissure that form the upper jaw. This is similar to the mandible , which is also a fusion of two halves at the mental symphysis. Sometimes The maxilla (plural: maxillae) is a fusion of two bones along the palatal fissure that form the upper...
and mandible (underdevelopment of the upper and lower jaw, respectively), with the maxilla more prominently affected in some cases; congenital clefting of bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s surrounding the optical orbit
Orbit (anatomy)
In anatomy, the orbit is the cavity or socket of the skull in which the eye and its appendages are situated. "Orbit" can refer to the bony socket, or it can also be used to imply the contents...
(eye socket), such as the frontal
Frontal bone
The frontal bone is a bone in the human skull that resembles a cockleshell in form, and consists of two portions:* a vertical portion, the squama frontalis, corresponding with the region of the forehead....
and lacrimal bone
Lacrimal bone
The lacrimal bone, the smallest and most fragile bone of the face, is situated at the front part of the medial wall of the orbit. It has two surfaces and four borders.-Lateral or orbital surface:...
; and maldeveloped deciduous teeth
Deciduous teeth
Deciduous teeth, otherwise known as reborner teeth, baby teeth, temporary teeth and primary teeth, are the first set of teeth in the growth development of humans and many other mammals. In some Asian countries they are referred to as fall teeth as they will eventually fall out, while in almost all...
("baby teeth"), with an absence of permanent teeth
Permanent teeth
Permanent teeth are the second set of teeth formed in humans. There are thirty-two permanent teeth, consisting of six maxillary and six mandibular molars, four maxillary and four mandibular premolars, two maxillary and two mandibular canines, four maxillary and four mandibular incisors.The first...
.
Effects on other organ systems
Additional congenital anomalies, effects on other organsOrgan (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
, and less common features of JBS have included: imperforate anus
Imperforate anus
An imperforate anus or anal atresia is a birth defect in which the rectum is malformed. Its cause is unknown.-Features:There are several forms of imperforate anus:* A low lesion, in which the colon remains close to the skin...
(occlusion of the anus
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...
), vesicoureteral reflux
Vesicoureteral reflux
Vesicoureteral reflux is an abnormal movement of urine from the bladder into ureters or kidneys. Urine normally travels from the kidneys via the ureters to the bladder...
(reversal of the flow of urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, from the bladder
Bladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
back into the ureter
Ureter
In human anatomy, the ureters are muscular tubes that propel urine from the kidneys to the urinary bladder. In the adult, the ureters are usually long and ~3-4 mm in diameter....
s, toward the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s); duplex of the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
and vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
in female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
infants, neonatal cholestasis
Neonatal cholestasis
Neonatal cholestasis defines persisiting conjugated hyperbilirubinemia in the newborn with conjugated bilirubin levels exceeding 15% of total bilirubin level. The disease is either due to defects in bile excretion from hepatocytes or impaired bile flow.The incidence has been found to be about...
of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, with cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
and portal hypertension
Portal hypertension
In medicine, portal hypertension is hypertension in the portal vein and its tributaries.It is often defined as a portal pressure gradient of 10 mmHg or greater.-Causes:Causes can be divided into prehepatic, intrahepatic, and posthepatic...
(high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
in the hepatic portal vein
Hepatic portal vein
The hepatic portal vein is not a true vein, because it does not conduct blood directly to the heart. It is a vessel in the abdominal cavity that drains blood from the gastrointestinal tract and spleen to capillary beds in the liver...
); dilated cardiomyopathy
Dilated cardiomyopathy
Dilated cardiomyopathy or DCM is a condition in which the heart becomes weakened and enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems....
, dextrocardia
Dextrocardia
Dextrocardia is a congenital defect in which the heart is situated on the right side of the body. There are two main types of dextrocardia: dextrocardia of embryonic arrest and dextrocardia situs inversus...
(congenital displacement of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
to the right side of the chest
Chest
The chest is a part of the anatomy of humans and various other animals. It is sometimes referred to as the thorax or the bosom.-Chest anatomy - Humans and other hominids:...
), atrial
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
and ventricular septal defect
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
; low birth-weight
Small for gestational age
Small for gestational age babies are those who are smaller in size than normal for the baby's sex and gestational age, most commonly defined as a weight below the 10th percentile for the gestational age.-Terminology:...
, failure to thrive
Failure to thrive
Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
, hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
(decreased muscle tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
); sacral hiatus
Sacral hiatus
The laminae of the fifth sacral vertebra, and sometimes those of the fourth, fail to meet behind, and thus a sacral hiatus occurs in the posterior wall of the sacral canal....
(a structural deficiency of the sacral vertebrae
Sacrum
In vertebrate anatomy the sacrum is a large, triangular bone at the base of the spine and at the upper and back part of the pelvic cavity, where it is inserted like a wedge between the two hip bones. Its upper part connects with the last lumbar vertebra, and bottom part with the coccyx...
), congenital cataracts
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
, and cafe-au-lait spots.
Pathophysiology
Johanson–Blizzard syndrome is caused by mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the UBR1
UBR1
The human gene UBR1 encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1.-Further reading:...
gene, which encodes one of several ubiquitin ligase
Ubiquitin ligase
A ubiquitin ligase is a protein that in combination with an E2 ubiquitin-conjugating enzyme causes the attachment of ubiquitin to a lysine on a target protein via an isopeptide bond; the E3 ubiquitin ligase targets specific protein substrates for degradation by the proteasome...
enzymes of the N-end rule pathway.
The protein ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
is a universal, "ubiquitously" expressed protein common to eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
s. Ubiquitin plays a role in the regulation
Post-translational regulation
Post-translational regulation refers to the control of the levels of active protein.There are several forms.It is performed either by means of reversible events or by means of irreversible events ....
of other proteins by tagging them for eventual degradation by proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
s. This process begins when ubiquitin ligase covalently
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....
attaches a ubiquitin molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
to the lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
of the target protein substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
(the misfolded, damaged, malfunctioning or unneeded protein that needs to be degraded). This is repeated a number of times in succession forming a chain of ubiquitin molecules, which is a process referred to as polyubiquitination. The polyubiquitination of the target protein signals the proteasome to break it down, which it does via proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
. The ubiquitin-proteasome system plays a crucial role in the non-lysosomal
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
degradation of intracellular proteins, and ubiquitin can also participate in modifying
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
proteins to perform certain tasks. Both degradation and modification of proteins within the cell are part of a broader regulatory scheme, necessary for cellular processes such as cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
, cell signalling, cell surface receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
function, apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
maintenance, inflammatory response and developmental quality control associated with the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
and homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
in general.
Ubiquitin-mediated degradation of proteins occurs through the N-end rule
N-end rule
The N-end rule is a rule related to ubiquitination, discovered by Alexander Varshavsky in 1986. The rule, which states that the nature of the N-terminal amino acids of a protein is an important factor that governs its half-life , is applicable to both eukaryotic and prokaryotic organisms, but with...
pathway. In eukaryotes, including humans, the N-end rule pathway is part of the ubiquitin system. Composed of a highly-selective single-residue
Residue (chemistry)
In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
code (a single amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
sequence), the N-end rule serves as a mechanism which can relate the stability of a protein to the identity of the amino acid at its N-terminus (the end of the polypeptide with an amino group, which in the ubiquitin system may be involved in the reactive destabilization of the protein).
In JBS, mutations in the UBR1 gene alter, disrupt or prevent the synthesis of ubiquitin ligase. In the pancreatic acinar cells, UBR1 is more highly expressed than anywhere else in the body. Impairment of the ubiquitin-proteasome system directly related to insufficient activity of ubiquitin ligase has been established as the cause of both congenital and progressive inflammatory damage, fatty tissue replacement, connective tissue proliferation and errors in innervation of the acini and islets, correlating to failures of normal apoptotic destruction of damaged cells and constitutive malpresence of proteins. This also applies to other areas affected by deleterious UBR1 expression, such as the craniofacial area, musculoskeletal and nervous systems, dentition and organs.
Missense
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
, nonsense
Nonsense mutation
In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...
and splice site mutation
Splice site mutation
A splice site mutation is a genetic mutation that inserts or deletes a number of nucleotides in the specific site at which splicing of an intron takes place during the processing of precursor messenger RNA into mature messenger RNA. The abolishment of the splicing site results in one or more...
s of the UBR1 gene in both parents have been found with JBS, confirming the homozygous nature of the JBS phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
. Variability of the phenotype, associated with residual ubiquitin ligase activity in some patients, has also been attributed to hypomorphic mutations occasionally found in either of the carrier parents. The UBR1 gene is located on human chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
15.
Treatment
While there is no cure for JBS, treatment and management of specific symptoms and features of the disorder are applied and can often be successful. Variability in the severity of JBS on a case-by-case basis determines the requirements and effectiveness of any treatment selected.Pancreatic insufficiency and malabsorption can be managed with pancreatic enzyme replacement therapy, such as pancrelipase
Pancrelipase
Pancrelipase is a form of enzyme therapy for the treatment of various digestive disorders, primarily exocrine pancreatic insufficiency. It is a mixture of three digestive enzymes, amylase, trypsin, and lipase, which are normally produced by the pancreas...
supplementation and other related methods.
Craniofacial and skeletal deformities may require surgical correction, using techniques including bone grafts and osteotomy
Osteotomy
An osteotomy is a surgical operation whereby a bone is cut to shorten, lengthen, or change its alignment. It is sometimes performed to correct a hallux valgus, or to straighten a bone that has healed crookedly following a fracture. It is also used to correct a coxa vara, genu valgum, and genu varum...
procedures. Sensorineural hearing loss can be managed with the use of hearing aid
Hearing aid
A hearing aid is an electroacoustic device which typically fits in or behind the wearer's ear, and is designed to amplify and modulate sound for the wearer. Earlier devices, known as "ear trumpets" or "ear horns", were passive funnel-like amplification cones designed to gather sound energy and...
s and educational services designated for the hearing impaired.
Special education, specialized counseling methods and occupational therapy
Occupational therapy
Occupational therapy is a discipline that aims to promote health by enabling people to perform meaningful and purposeful activities. Occupational therapists work with individuals who suffer from a mentally, physically, developmentally, and/or emotionally disabling condition by utilizing treatments...
designed for those with mental retardation have proven to be effective, for both the patient and their families. This, too, is carefully considered for JBS patients.
Genetics
JBS is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
Genetic carrier
A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Eponym
Johanson–Blizzard syndrome was named after Drs. A. J. Johanson and Robert M. BlizzardRobert M. Blizzard
Robert M. Blizzard was a pediatric endocrinologist and a founding member of the Lawson Wilkins Pediatric Endocrine Society.-References:...
, who first described the disorder in a 1971 journal report.