Gerodermia osteodysplastica
Encyclopedia
Gerodermia osteodysplastica (GO), also called geroderma osteodysplasticum and Walt Disney dwarfism, is a rare autosomal
recessive connective tissue disorder
included in the spectrum of cutis laxa
syndrome
s.
Usage of the name "Walt Disney dwarfism" is attributed to the first known case of the disorder, documented in a 1950 journal report, in which the authors described five affected members from a Swiss
family as having the physical appearance of dwarves from a Walt Disney
film.
The terms "geroderma" or "gerodermia" can be used interchangeably with "osteodysplastica" or "osteodysplasticum", with the term "hereditaria" sometimes appearing at the end.
s, skin
and skeletal system.
These are: wrinkly, loose skin over the face
, abdomen
, and extremites (hand
s, feet) on the dorsal
sides usually worsened by chronic joint
laxity and hyperextensibility; fragmented elastic fibers of the skin that are reduced in number, with disorientation of collagen fibers
; osteopenia
and osteoporosis
, with associated fractures
; malar
hypoplasia
(underdeveloped cheek bone), maxilla
ry hypoplasia (underdeveloped upper jaw
), mandibular prognathism (protrusion of the lower jaw and chin
), bowed long bone
s, platyspondyly (flattened spine
) related to vertebral collapse; kyphoscoliosis
(scoliosis
with kyphosis
, or "hunch back"), metaphyseal
peg (an unusual outgrowth of metaphyseal tissue which protrudes into the epiphyseal
region of the bone, near the knee
); and the overall physical effects and facial appearance of dwarfism
with premature aging.
Other features and findings include: intrauterine
growth retardation, congenital
hip dislocations, winged scapula
e (shoulder blades
), pes planus
(fallen arches
), pseudoepiphyses of the second metacarpals (upper bone of the finger
s), hypotelorism
(close-set eye
s), malformed ear
s,
developmental delay
,
failure to thrive
and abnormal electroencephalograph
(EEG) readings.
Dental and orthodontal
abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. Including malocclusion
of the dental arches
(the maxilla and mandible), radiological
findings in some cases have indicated significant overgrowth of the mandibular premolar
and molar
roots;
hypercementosis
(overproduction of cementum
) of the molars and maxillary incisor
s; enlarged, funnel-shaped mandibular lingula
(spiny structures on the ramus of the mandible); and a radiolucent
effect on portions of many teeth
, increasing their transparency to x-ray
s.
(WSS, ), are similar to such an extent that both disorders were believed to be variable phenotype
s of a single disorder.
Several delineating factors, however, suggest that gerodermia osteodysplastica and wrinkly skin syndrome are distinct entities, but share the same clinic spectrum.
While the prevailing feature of wrinkly, loose skin is more localized with GO, it is usually systemic, yet eases in severity with age during the course of WSS. Also, as the fontanelle
s ("soft spots") are usually normal on the heads of infant
s with GO, they are often enlarged in WSS infants.
Although WSS is associated with mutation
s of gene
s on chromosome
s 2, 5, 7, 11 and 14; no genetic mutation has been established for GO. A serum
sialotransferrin type 2 pattern, also observed with WSS, is not present in GO patients.
But perhaps the most notable feature, differentiating GO from WSS and similar cutis laxa disorders, is the age-specific metaphyseal peg sometimes found in GO-affected long bone, near the knee. Not appearing until around age 4–5, then disappearing by physeal closure, this oddity of bone is thought to represent a specific genetic marker unique to GO and its effects on bone development.
Originally believed to be inherited in an X-linked recessive
fashion, gerodermia osteodysplastica is now known to display strictly autosomal recessive inheritance. 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.
It has been associated with SCYL1BP1.
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 connective tissue disorder
Connective tissue disease
A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs...
included in the spectrum of cutis laxa
Cutis laxa
Cutis laxa is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.-Causes:In most cases, cutis laxa is inherited...
syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
s.
Usage of the name "Walt Disney dwarfism" is attributed to the first known case of the disorder, documented in a 1950 journal report, in which the authors described five affected members from a Swiss
Switzerland
Switzerland name of one of the Swiss cantons. ; ; ; or ), in its full name the Swiss Confederation , is a federal republic consisting of 26 cantons, with Bern as the seat of the federal authorities. The country is situated in Western Europe,Or Central Europe depending on the definition....
family as having the physical appearance of dwarves from a Walt Disney
Walt Disney Pictures
Walt Disney Pictures is an American film studio owned by The Walt Disney Company. Walt Disney Pictures and Television, a subsidiary of the Walt Disney Studios and the main production company for live-action feature films within the Walt Disney Motion Pictures Group, based at the Walt Disney...
film.
The terms "geroderma" or "gerodermia" can be used interchangeably with "osteodysplastica" or "osteodysplasticum", with the term "hereditaria" sometimes appearing at the end.
Characteristics
Gerodermia osteodysplastica is characterized by symptoms and features which affect the connective tissueConnective 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...
s, 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...
and skeletal system.
These are: wrinkly, loose skin over the 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...
, abdomen
Abdomen
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
, and extremites (hand
Hand
A hand is a prehensile, multi-fingered extremity located at the end of an arm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs...
s, feet) on the dorsal
Dorsum (biology)
In anatomy, the dorsum is the upper side of animals that typically run, fly, or swim in a horizontal position, and the back side of animals that walk upright. In vertebrates the dorsum contains the backbone. The term dorsal refers to anatomical structures that are either situated toward or grow...
sides usually worsened by chronic joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
laxity and hyperextensibility; fragmented elastic fibers of the skin that are reduced in number, with disorientation of collagen fibers
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
; osteopenia
Osteopenia
Osteopenia is a condition where bone mineral density is lower than normal. It is considered by many doctors to be a precursor to osteoporosis. However, not every person diagnosed with osteopenia will develop osteoporosis...
and osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
, with associated fractures
Bone fracture
A bone fracture is a medical condition in which there is a break in the continuity of the bone...
; malar
Zygomatic bone
The zygomatic bone is a paired bone of the human skull. It articulates with the maxilla, the temporal bone, the sphenoid bone and the frontal bone. The zygomatic is homologous to the jugal bone of other tetrapods...
hypoplasia
Hypoplasia
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...
(underdeveloped cheek bone), 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...
ry hypoplasia (underdeveloped upper 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...
), mandibular prognathism (protrusion of the lower jaw and chin
Chin
In the human anatomy, the chin is the lowermost part of the face.It is formed by the lower front of the mandible.People show a wide variety of chin structures. See Cleft chin....
), bowed long bone
Long bone
The long bones are those that are longer than they are wide. They are one of five types of bones: long, short, flat, irregular and sesamoid. Long bones, especially the femur and tibia, are subjected to most of the load during daily activities and they are crucial for skeletal mobility. They grow...
s, platyspondyly (flattened spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
) related to vertebral collapse; kyphoscoliosis
Kyphoscoliosis
Kyphoscoliosis describes an abnormal curvature of the spine in both a coronal and sagittal plane. It is a combination of kyphosis and scoliosis. Kyphoscoliosis is a musculoskeletal disorder causing chronic underventilation of the lungs and may be one of the major causes of pulmonary hypertension...
(scoliosis
Scoliosis
Scoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
with kyphosis
Kyphosis
Kyphosis , also called roundback or Kelso's hunchback, is a condition of over-curvature of the thoracic vertebrae...
, or "hunch back"), metaphyseal
Metaphysis
The metaphysis is the wider portion of a long bone adjacent to the epiphyseal plate. It is this part of the bone that grows during childhood; as it grows, it ossifies near the diaphysis and the epiphyses...
peg (an unusual outgrowth of metaphyseal tissue which protrudes into the epiphyseal
Epiphysis
The epiphysis is the rounded end of a long bone, at its joint with adjacent bone. Between the epiphysis and diaphysis lies the metaphysis, including the epiphyseal plate...
region of the bone, near the knee
Knee
The knee joint joins the thigh with the leg and consists of two articulations: one between the fibula and tibia, and one between the femur and patella. It is the largest joint in the human body and is very complicated. The knee is a mobile trocho-ginglymus , which permits flexion and extension as...
); and the overall physical effects and facial appearance of 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....
with premature aging.
Other features and findings include: intrauterine
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...
growth retardation, congenital
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...
hip dislocations, winged scapula
Scapula
In anatomy, the scapula , omo, or shoulder blade, is the bone that connects the humerus with the clavicle ....
e (shoulder blades
Shoulder
The human shoulder is made up of three bones: the clavicle , the scapula , and the humerus as well as associated muscles, ligaments and tendons. The articulations between the bones of the shoulder make up the shoulder joints. The major joint of the shoulder is the glenohumeral joint, which...
), pes planus
Flat feet
Flat feet is a formal reference to a medical condition in which the arch of the foot collapses, with the entire sole of the foot coming into complete or near-complete contact with the ground...
(fallen arches
Arches of the foot
-External links:* * *...
), pseudoepiphyses of the second metacarpals (upper bone of the finger
Finger
A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates....
s), hypotelorism
Hypotelorism
-Causes:It is often a result of fetal alcohol syndrome caused by large alcohol intake in the first month of pregnancy.It can be associated with trisomy 8.It can also be associated with fragile X syndrome....
(close-set eye
Eye
Eyes are organs that detect light and convert it into electro-chemical impulses in neurons. The simplest photoreceptors in conscious vision connect light to movement...
s), malformed 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,
developmental delay
Delayed milestone
Delayed milestone, also called developmental delays, is used to describe the condition where a child does not reach one of these stages at the expected age. However, in most cases, a wide variety of ages can be considered normal, and not a cause for medical concern...
,
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 ....
and abnormal electroencephalograph
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...
(EEG) readings.
Dental and orthodontal
Orthodontics
Orthodontics, orthodontia, or orthodonture is the first specialty of dentistry that is concerned with the study and treatment of malocclusions , which may be a result of tooth irregularity, disproportionate jaw relationships, or both...
abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. Including malocclusion
Malocclusion
A malocclusion is a misalignment of teeth or incorrect relation between the teeth of the two dental arches. The term was coined by Edward Angle, the "father of modern orthodontics", as a derivative of occlusion, which refers to the manner in which opposing teeth meet.-Presentation:Most people have...
of the dental arches
Dental arches
The superior dental arch is larger than the inferior, so that in the normal condition the teeth in the maxillae slightly overlap those of the mandible both in front and at the sides....
(the maxilla and mandible), radiological
Radiology
Radiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...
findings in some cases have indicated significant overgrowth of the mandibular premolar
Premolar
The premolar teeth or bicuspids are transitional teeth located between the canine and molar teeth. In humans, there are two premolars per quadrant, making eight premolars total in the mouth. They have at least two cusps. Premolars can be considered as a 'transitional tooth' during chewing, or...
and molar
Molar (tooth)
Molars are the rearmost and most complicated kind of tooth in most mammals. In many mammals they grind food; hence the Latin name mola, "millstone"....
roots;
hypercementosis
Hypercementosis
Etiology of Hypercementosis can be caused by many things. A way to remember the causes is "PIG ON TAP" -PagetsIdiopathicGigantismOccusal TraumaNon functional toothTraumaAcromegliaPeriapical granuloma...
(overproduction of cementum
Cementum
Cementum is a specialized calcified substance covering the root of a tooth. Cementum is excreted by cells called cementoblasts within the root of the tooth and is thickest at the root apex. These cementoblasts develop from undifferentiated mesenchymal cells in the connective tissue of the dental...
) of the molars and maxillary incisor
Incisor
Incisors are the first kind of tooth in heterodont mammals. They are located in the premaxilla above and mandible below.-Function:...
s; enlarged, funnel-shaped mandibular lingula
Lingula of mandible
The margin of the mandibular foramen is irregular; it presents in front a prominent ridge, surmounted by a sharp spine, the lingula of the mandible which gives attachment to the sphenomandibular ligament; at its lower and back part is a notch from which the mylohyoid groove runs obliquely downward...
(spiny structures on the ramus of the mandible); and a radiolucent
Radiodensity
Radiodensity refers to the relative inability of electromagnetic radiation, particularly X-rays, to pass through a particular material. Radiolucency indicates greater transparency or "transradiancy" to X-ray photons...
effect on portions of many teeth
Tooth
Teeth are small, calcified, whitish structures found in the jaws of many vertebrates that are used to break down food. Some animals, particularly carnivores, also use teeth for hunting or for defensive purposes. The roots of teeth are embedded in the Mandible bone or the Maxillary bone and are...
, increasing their transparency to x-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s.
Differential diagnosis
Many features of gerodermia osteodysplastica (GO) and another autosomal recessive form of cutis laxa, wrinkly skin syndromeWrinkly skin syndrome
Wrinkly skin syndrome is a hereditary connective tissue disorder that is inherited in an autosomal recessive fashion....
(WSS, ), are similar to such an extent that both disorders were believed to be variable 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...
s of a single disorder.
Several delineating factors, however, suggest that gerodermia osteodysplastica and wrinkly skin syndrome are distinct entities, but share the same clinic spectrum.
While the prevailing feature of wrinkly, loose skin is more localized with GO, it is usually systemic, yet eases in severity with age during the course of WSS. Also, as the 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...
s ("soft spots") are usually normal on the heads of 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 with GO, they are often enlarged in WSS infants.
Although WSS is associated with mutation
Mutation
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 of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s on 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...
s 2, 5, 7, 11 and 14; no genetic mutation has been established for GO. A serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
sialotransferrin type 2 pattern, also observed with WSS, is not present in GO patients.
But perhaps the most notable feature, differentiating GO from WSS and similar cutis laxa disorders, is the age-specific metaphyseal peg sometimes found in GO-affected long bone, near the knee. Not appearing until around age 4–5, then disappearing by physeal closure, this oddity of bone is thought to represent a specific genetic marker unique to GO and its effects on bone development.
Inheritance
Originally believed to be inherited in an X-linked recessive
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 expressed in males and in females who are homozygous for the gene mutation X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on...
fashion, gerodermia osteodysplastica is now known to display strictly autosomal recessive inheritance. 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.
It has been associated with SCYL1BP1.