Gerodermia osteodysplastica (GO) is a rare

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

connective tissue disorder A connective tissue disease (collagenosis) 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 togeth ...

included in the spectrum of

cutis laxa Cutis laxa or pachydermatocele is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds. Signs and symptoms It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasti ...

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...

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 Swiss may refer to: * the adjectival form of Switzerland * Swiss people Places * Swiss, Missouri * Swiss, North Carolina *Swiss, West Virginia * Swiss, Wisconsin Other uses *Swiss-system tournament, in various games and sports *Swiss Internation ...

family as having the physical appearance of dwarves from a

Walt Disney Walter Elias Disney (; December 5, 1901December 15, 1966) was an American animator, film producer and entrepreneur. A pioneer of the American animation industry, he introduced several developments in the production of cartoons. As a film p ...

film. The terms "geroderma" or "gerodermia" can be used interchangeably with "osteodysplastica" or "osteodysplasticum", with the term "hereditaria" sometimes appearing at the end.

Presentation

Gerodermia osteodysplastica is characterized by symptoms and features which affect the

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

and

skeletal system A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

. These are: wrinkly, loose skin over the

face The face is the front of an animal's head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human identity, and damage such as scarring or developmental deformities may aff ...

abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. ...

, and extremities (

hand A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the koala (which has two opposable thumbs on each "h ...

s, feet) on the

dorsal Dorsal (from Latin ''dorsum'' ‘back’) may refer to: * Dorsal (anatomy), an anatomical term of location referring to the back or upper side of an organism or parts of an organism * Dorsal, positioned on top of an aircraft's fuselage * Dorsal co ...

sides usually worsened by chronic

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...

laxity and hyperextensibility; fragmented

elastic fiber Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix composed of bundles of proteins (elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and air ...

s of the skin that are reduced in number, with disorientation of

collagen fibers Type I collagen is the most abundant collagen of the human body. It forms large, eosinophilic fibers known as collagen fibers. It is present in scar tissue, the end product when tissue heals by repair, as well as tendons, ligaments, the endomys ...

;

osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteop ...

and

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

, with associated

fractures Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...

; malar

hypoplasia Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.maxilla The maxilla (plural: ''maxillae'' ) in vertebrates is the upper fixed (not fixed in Neopterygii) bone of the jaw formed from the fusion of two maxillary bones. In humans, the upper jaw includes the hard palate in the front of the mouth. The t ...

ry hypoplasia (underdeveloped upper

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 serv ...

mandibular In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower teeth in place. The mandible sits beneath the maxilla. It is the only movable bone ...

prognathism Prognathism, also called Habsburg jaw or Habsburgs' jaw primarily in the context of its prevalence amongst members of the House of Habsburg, is a positional relationship of the mandible or maxilla to the skeletal base where either of the jaws pr ...

(protrusion of the lower jaw and

chin The chin is the forward pointed part of the anterior mandible (List_of_human_anatomical_regions#Regions, mental region) below the lower lip. A fully developed human skull has a chin of between 0.7 cm and 1.1 cm. Evolution The presence of a we ...

), bowed

long bone The long bones are those that are longer than they are wide. They are one of five types of bones: long, Short bone, short, Flat bone, flat, Irregular bone, irregular and Sesamoid bone, sesamoid. Long bones, especially the femur and tibia, are subj ...

platyspondyly Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condi ...

(flattened

spine Spine or spinal may refer to: Science Biology * Vertebral column, also known as the backbone * Dendritic spine, a small membranous protrusion from a neuron's dendrite * Thorns, spines, and prickles, needle-like structures in plants * Spine (zoolog ...

) related to

vertebra The spinal column, a defining synapomorphy shared by nearly all vertebrates,Hagfish are believed to have secondarily lost their spinal column is a moderately flexible series of vertebrae (singular vertebra), each constituting a characteristic ...

l collapse;

kyphoscoliosis Kyphoscoliosis describes an abnormal curvature of the spine in both a coronal and sagittal plane. It is a combination of kyphosis and scoliosis. This musculoskeletal disorder often leads to other issues in patients, such as under-ventilation of ...

(

scoliosis Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...

with

kyphosis Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave ''lordotic'' curving of the cervical and lumbar regions of the spine is called lordosis. It can result fr ...

, or "hunch back"),

metaphyseal The metaphysis is the neck portion of a long bone between the epiphysis and the diaphysis. It contains the growth plate, the part of the bone that grows during childhood, and as it grows it ossifies near the diaphysis and the epiphyses. The metaph ...

peg (an unusual outgrowth of metaphyseal tissue which protrudes into the

epiphyseal The epiphysis () is the rounded end of a long bone, at its joint with adjacent bone(s). Between the epiphysis and diaphysis (the long midsection of the long bone) lies the metaphysis, including the epiphyseal plate (growth plate). At the joi ...

region of the bone, near the

knee In humans and other primates, the knee joins the thigh with the leg and consists of two joints: one between the femur and tibia (tibiofemoral joint), and one between the femur and patella (patellofemoral joint). It is the largest joint in the hu ...

); and the overall physical effects and facial appearance of

dwarfism Dwarfism is a condition wherein an organism is exceptionally small, and mostly occurs in the animal kingdom. In humans, it is sometimes defined as an adult height of less than , regardless of sex; the average adult height among people with dw ...

with premature aging. Other features and findings include:

intrauterine The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

growth retardation,

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 ...

hip In vertebrate anatomy, hip (or "coxa"Latin ''coxa'' was used by Celsus in the sense "hip", but by Pliny the Elder in the sense "hip bone" (Diab, p 77) in medical terminology) refers to either an anatomical region or a joint. The hip region is ...

dislocations In materials science, a dislocation or Taylor's dislocation is a linear crystallographic defect or irregularity within a crystal structure that contains an abrupt change in the arrangement of atoms. The movement of dislocations allow atoms to sl ...

, winged

scapula The scapula (plural scapulae or scapulas), also known as the shoulder blade, is the bone that connects the humerus (upper arm bone) with the clavicle (collar bone). Like their connected bones, the scapulae are paired, with each scapula on eithe ...

e ( shoulder blades),

pes planus Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born ...

(fallen

arches An arch is a vertical curved structure that spans an elevated space and may or may not support the weight above it, or in case of a horizontal arch like an arch dam, the hydrostatic pressure against it. Arches may be synonymous with vault ...

), pseudoepiphyses of the second

metacarpals In human anatomy, the metacarpal bones or metacarpus form the intermediate part of the skeleton, skeletal hand located between the phalanges of the fingers and the carpal bones of the wrist, which forms the connection to the forearm. The metacarpa ...

(upper bone of the

finger A finger is a limb of the body and a type of digit, an organ of manipulation and sensation found in the hands of most of the Tetrapods, so also with humans and other primates. Most land vertebrates have five fingers ( Pentadactyly). Chambers ...

s),

hypotelorism Hypotelorism is an abnormally decreased distance between two organs or bodily parts, usually pertaining to the eye sockets (orbits), also known as orbital hypotelorism. Causes It is often a result of fetal alcohol syndrome (FAS), caused by lar ...

(close-set

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

s), malformed

ear An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, c ...

failure to thrive Failure to thrive (FTT), also known as weight faltering or faltering growth, indicates insufficient weight gain or absence of appropriate physical growth in children. FTT is usually defined in terms of weight, and can be evaluated either by a low ...

and abnormal

electroencephalograph Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

(EEG) readings. Dental and orthodontal abnormalities in addition to maxillary hypoplasia and mandibular prognathism have also been observed in gerodermia osteodysplastica. Including

malocclusion In orthodontics, a malocclusion is a misalignment or incorrect relation between the teeth of the upper and lower dental arches when they approach each other as the jaws close. The English-language term dates from 1864; Edward Angle (1855-1930), ...

of the dental arches (the maxilla and mandible),

radiological In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visib ...

findings in some cases have indicated significant overgrowth of the mandibular

premolar The premolars, also called premolar teeth, or bicuspids, are transitional teeth located between the canine and molar teeth. In humans, there are two premolars per quadrant in the permanent set of teeth, making eight premolars total in the mouth ...

and molar roots;

hypercementosis Hypercementosis is an idiopathic, non-neoplastic condition characterized by the excessive buildup of normal cementum (calcified tissue) on the roots of one or more teeth. A thicker layer of cementum can give the tooth an enlarged appearance, which ...

(overproduction of

cementum Cementum is a specialized calcified substance covering the root of a tooth. The cementum is the part of the periodontium that attaches the teeth to the alveolar bone by anchoring the periodontal ligament.Illustrated Dental Embryology, Histology, a ...

) of the molars and maxillary

incisor Incisors (from Latin ''incidere'', "to cut") are the front teeth present in most mammals. They are located in the premaxilla above and on the mandible below. Humans have a total of eight (two on each side, top and bottom). Opossums have 18, whe ...

s; enlarged, funnel-shaped mandibular lingula (spiny structures on the

ramus of the mandible In anatomy, the mandible, lower jaw or jawbone is the largest, strongest and lowest bone in the human facial skeleton. It forms the lower jaw and holds the lower teeth in place. The mandible sits beneath the maxilla. It is the only movable bone ...

); and a

radiolucent Radiodensity (or radiopacity) is opacity to the radio wave and X-ray portion of the electromagnetic spectrum: that is, the relative inability of those kinds of electromagnetic radiation to pass through a particular material. Radiolucency or hypod ...

effect on portions of many

teeth A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...

, increasing their transparency to

x-ray An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nb ...

Genetics

Originally believed to be inherited in an

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

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 An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

, 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 Carry or carrying may refer to: People *Carry (name) Finance * Carried interest (or carry), the share of profits in an investment fund paid to the fund manager * Carry (investment), a financial term: the carry of an asset is the gain or cost of h ...

one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. It has been associated with '' SCYL1BP1''.

Diagnosis

Differential diagnosis

Many features of gerodermia osteodysplastica (GO) and another autosomal recessive form of cutis laxa,

wrinkly skin syndrome Wrinkly skin syndrome (WSS) is a rare genetic condition characterized by sagging, wrinkled skin, low skin elasticity, and delayed fontanelle (soft spot) closure, along with a range of other symptoms. The disorder exhibits an autosomal recessive in ...

(WSS, '), are similar to such an extent that both disorders were believed to be variable

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

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 A fontanelle (or fontanel) (colloquially, soft spot) is an anatomical feature of the infant human skull comprising soft membranous gaps ( sutures) between the cranial bones that make up the calvaria of a fetus or an infant. Fontanelles allow f ...

s ("soft spots") are usually normal on the heads of

infant An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

s with GO, they are often enlarged in WSS infants. While WSS is associated with

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s of

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

s on

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

s 2, 5, 7, 11 and 14; GO has been linked to mutations in the protein GORAB. 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 A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...

unique to GO and its effects on bone development.

Treatment

References

External links

{{Congenital malformations and deformations of integument Autosomal recessive disorders Connective tissue diseases Abnormalities of dermal fibrous and elastic tissue Skeletal disorders Orthodontics Rare diseases