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Skeletal Dysplasia


Skeletal dysplasia, also termed osteochondrodysplasia, refers to a general disorder affecting cartilage and bone. There are more than 200 forms of skeletal dysplasia, the most common symptoms being a short stature, disproportional size and altered shape of bones. Most forms of skeletal dysplasia are genetic diseases.


Pain and deformities may be noted in any part of the body. While abnormal development and growth of the skeleton of the limbs generally results in a short overall stature, disproportions and restricted motor skills, alterations regarding the skeleton of the trunk may yield respiratory, neurologic and sometimes even cardiovascular problems. A short trunk, airway obstruction and a certain degree of neurological deficits due to abnormal development of the spine are not uncommon in SD patients. Spine deformation may result in abnormal posture, but also in paraparesis or quadriparesis. Cardiac defects can be seen in patients suffering from chondroectodermal dysplasia, the short rib polydactyly syndrome and the Larsen syndrome [20] [21] [22].

There is a rule of thumb to distinguish SD from endocrine disorders and deficient nutrition: Both are frequently associated with a short stature, but disproportions are characteristic for SD. Growth retardation is usually proportional in patients suffering from endocrine, metabolic or immune disorders and deficient nutrition. However, there are exceptions to this rule. For instance, osteogenesis imperfecta, one of the most frequently occurring forms of SD, may be associated with relatively normal body proportions.

Dysmorphic Face
  • Lethal short limb dwarfism with dysmorphic face, omphalocele and severe ossification defect: Piepkorn syndrome or severe “boomerang dysplasia”?. Ann Genet 1992; 35 : 129–133. 33. Cormier-Daire V, Savarirayan R, Unger S, Rimoin DL, Lachman RS.[nature.com]
Broad Chest
  • Her anomalies consisted of disproportionately short stature, short neck, broad and depressed nasal bridge, broad chest in the anteroposterior dimension, kyphosis, widely spaced nipples, and protruded abdomen.[ncbi.nlm.nih.gov]
Failure to Thrive
  • In addition, he presented with very severe prenatal growth failure, respiratory distress as a neonate, subsequent failure to thrive and susceptibility to airway infection, and sudden death in early childhood.[ncbi.nlm.nih.gov]
  • The phenotype is characterized by brachycephaly, flat face, hypertelorism, low-set ears, hypertrichosis, hypoplastic thorax, as well as short extremities with brachydactyly.[ncbi.nlm.nih.gov]
Widely Spaced Nipples
  • Her anomalies consisted of disproportionately short stature, short neck, broad and depressed nasal bridge, broad chest in the anteroposterior dimension, kyphosis, widely spaced nipples, and protruded abdomen.[ncbi.nlm.nih.gov]
Social Isolation
  • Social isolation is not uncommon in SD patients and affected persons usually have to confront social problems associated with disability.[symptoma.com]
Thin Lips
  • Dysmorphic features included broad nose, thick ears, thin lips, micrognathia, inverted nipples, ulnar deviation at the wrists, spatulate fingers, fifth finger camptodactyly, nail hypoplasia, and talipes equinovarus.[ncbi.nlm.nih.gov]
Large Anterior Fontanels
  • Cortical bones as well as vertebral endplates are thick and the skull is sclerotic with prominent parietal bones and a large anterior fontanel.[ncbi.nlm.nih.gov]
Beak Nose
  • Craniofacial anomalies included a sloping forehead, bitemporal bulging, sparse medial eyebrows, a prominent nasal bridge, hypertelorism, proptosis, a beaked nose, hypoplastic alae nasi and a pointed chin.[ncbi.nlm.nih.gov]
Beaked Nose
  • Craniofacial anomalies included a sloping forehead, bitemporal bulging, sparse medial eyebrows, a prominent nasal bridge, hypertelorism, proptosis, a beaked nose, hypoplastic alae nasi and a pointed chin.[ncbi.nlm.nih.gov]
Pointed Chin
  • Craniofacial anomalies included a sloping forehead, bitemporal bulging, sparse medial eyebrows, a prominent nasal bridge, hypertelorism, proptosis, a beaked nose, hypoplastic alae nasi and a pointed chin.[ncbi.nlm.nih.gov]


Any alterations detected during routine prenatal screenings and ultrasound examinations may indicate further diagnostics. Radiography, computed tomography, magnetic resonance imaging and molecular biologic diagnostics may be required to correctly diagnose a certain form of SD and to associate a prognosis. Such diagnostics may also be indicated in pregnant women who previously delivered a child suffering from any form of SD. Postnatally, additional clinical examinations, blood and urine tests gain importance. A family history of SD should prompt the corresponding examinations in early childhood, since diagnostics may be complicated after epiphyseal closure [23].

Pathologic alterations detected by diagnostic imaging techniques are usually the first indication of SD. Prenatally, three-dimensional imaging may be of great value to detect possible craniofacial anomalies. Postnatal radiography should be carried out thoroughly and include anteroposterior imaging of skull, chest, spine, pelvis and limbs. Skull and spine deformations can be detected in many forms of SD. In achondroplasia, for instance, the skull is usually pathologically large. Spine deformities often consist in alterations regarding vertebrae and overall course of the spine. In order to detect spinal curvatures, a laterolateral X-ray examination of the spine should also be done [24]. Pathologic findings regarding the epiphyseal plates of the long bones should prompt additional imaging of arms and legs. Also, metaphyseal or diaphyseal changes may trigger bone shortening and should therefore be watched out for. All types of limb shortening may be detected in specific forms of SD, i.e. rhizomelic, mesomelic, acromelic and micromelic extremities may be present. These consist in shortening of the proximal, middle or distal or of all parts of the limb, respectively.

Computed tomography and magnetic resonance imaging are mainly applied in order to examine the head and to evaluate if there are any brain anomalies. Magnetic resonance imaging may also be used to further evaluate spine deformities, e.g. Achondroplasia and Kniest dysplasia may be associated with atlantoaxial instability.

Laboratory tests of blood and urine may reveal alterations pointing towards specific forms of SD. As such, severe congenital hypophosphatasia is usually associated with reduced serum concentrations of alkaline phosphatase and increased urinary phosphorylethanolamine. Thanatophoric dysplasia and Kniest dysplasia are usually accompanied by an increase in urinary glycosaminoglycan. Blood screens may also be helpful to distinguish SD from endocrine, metabolic, immune and nutritional disorders. Of note, while SD is frequently associated with disproportional growth, the latter are not.

Even though most forms of SD are diagnosed early in life, diseases evolve over the course of life. In this context, follow-up examinations are indicated. Any findings should be contrasted with the ones obtained in previous examinations, images should be compared directly with each other [25]. This way, possibly arising complications may be detected early.

Increased Bone Density
  • Further characteristics are severe fetal hydrops, radiologic signs of increased bone density and short, poorly modeled tubular bones with wide diaphysis and smooth, rounded metaphyses.[ncbi.nlm.nih.gov]
Delayed Bone Age
  • Marques et al. [ 74 ] reported a 10-year-old girl with two heterozygous nonsense TRPS1 mutations with significantly reduced growth velocity and delayed bone age.[intechopen.com]
  • Other features included short stature, microcephaly, psychomotor retardation, B-cell lymphopenic hypogammaglobulinemia, sensorineural deafness, retinal detachment and blindness, intestinal malrotation with poor gastrointestinal motility, persistent hyponatremia[ncbi.nlm.nih.gov]


Prenatal detection of SD should prompt the corresponding decision regarding pregnancy and delivery. In some cases, a Caesarean section should be preferred over vaginal delivery to minimize the risk for injuries. Such is the case in children prenatally diagnosed with achondroplasia, because their head is often abnormally large and CNS damage and birth complications may result from vaginal delivery. Atlantoaxial instability, as described for Achondroplasia and Kniest dysplasia, also justifies a Caesarean section.

Causal treatment is not available. Neonates suffering from lethal SD may benefit from life-sustaining measures, but usually die within hours after birth. With regards to non-lethal SD, lifestyle adaptations, safety measures and supportive treatment is indicated to avoid further orthopedic and neurologic complications and pain.


Prognosis strongly depends on the specific form of SD and may range from infaust to excellent.

Certain forms of SD are lethal, resulting in intrauterine or perinatal death. SD accounts for about 1% of overall neonatal mortality. Non-lethal SD may be associated with reduced, near-normal or normal life expectancy. The degree of skeletal abnormalities and possibly of comorbidities that affect other organ systems is of great significance when informing about a prognosis. Therefore, a thorough clinical examination and diagnostic imaging are required.

Whereas prognosis quoad vitam may be excellent, that may not be the case for psychological health and social acceptance. Medical complications are as much of importance in SD patients as social consequences [19]. Problems may arise regarding the establishment of interpersonal relationships, sexual relations, building a family and more. Access to equal education and employment may be complicated, but is more of a social problem than a medical one unless the patient is suffering from severe skeletal abnormalities. Social isolation is not uncommon in SD patients and affected persons usually have to confront social problems associated with disability.


SD provoked by genetic defects may be inherited with a recessive or dominant trait and may be linked to autosomes or the X-chromosome. The precise genetic alteration triggering the disease has been identified for a large share of known forms of SD.

Other forms of SD have been associated with epigenetic phenomenons such as imprinting errors or exposure to teratogens. The latter may cause postzygotic mutations leading to somatic mosaicism or otherwise restrict development and growth [3] [8] [9] [10] [11].


Epidemiologic data is available regarding specific forms of SD as well as the group of diseases as a whole.

While approximately 1 in 10,000 children suffers from lethal SD, at least 2 in 10,000 children is born with some type of SD [12] [13]. It has been speculated that the true incidence of SD surpasses this value because some disorders do not manifest until childhood, adolescence or even more advanced ages. SD are a very heterogeneous group of diseases and although diagnosis usually occurs in newborns and young children, this does not apply to all forms of SD [5]. In this context, incidences of up to 8 per 10,000 have been reported [6] [13] [14] [15] [16].

The most common forms of SD are achondrogenesis, thanatophoric dysplasia, achondroplasia and osteogenesis imperfecta. Achondrogenesis and thanatophoric dysplasia are most often lethal, while achondroplasia and osteogenesis imperfecta are not.

With regards to autosomal SD, males and females are affected equally. Non-dominant forms of SD linked to the X-chromosome affect more men than women and may be lethal to males.

Sex distribution
Age distribution


Genetic defects leading to SD affect genes whose gene products may be grouped according to their function [17]. This is of clinical importance since defective proteins with related functions usually result in similar disturbances of development and growth [18].

Skeletal growth largely relies on the epiphyseal plates located between metaphysis and epiphysis of the long bones. The epiphyseal plate is a hyaline cartilage plate and the place of enchondral ossification; it is anatomically structured into several zones whose cells fulfill distinct functions. Many forms of SD do affect the epiphyseal plates and do thereby impair enchondral ossification and bone growth.

Other types of SD do affect the synthesis of connective tissue fibers and smaller matrix components. Based on their clinical characteristics, such forms of SD may be grouped as spondyloepiphyseal dysplasias and epiphyseal dysplasias.


Reproductive counseling may be of help to reduce the risk for a possible offspring developing SD. Such counseling is usually indicated when a family history of SD is present but depends on an exact diagnosis and knowledge regarding the disease's mode of inheritance.

Prenatal screenings allow an early diagnosis of possible SD and enable medical care givers to make the corresponding decisions regarding pregnancy and possible delivery. This also applies to routine medical check-ups of infants.


Skeletal dysplasia (SD) is a general term describing a wide variety of disorders affecting the skeleton. Contrary to dysostoses, the pathologic alterations in SD are generalized and not limited to a single bone or a group of bones. There are more than 350 diseases classified as SD or dysostosis, and approximately 200 belong to the former group [1] [2] [3]. Comprehensive classification systems have been developed to group these diseases [4] [5]. The incidence of each SD is low, but the incidence of SD in general amounts to approximately 2 in 10,000 [6].

Although most forms of SD may be classified as genetic diseases, among which there are single gene disorders, chromosome alterations, disorders that are inherited with a recessive or dominant trait [7], others occur due to exposure to teratogens or pathological conditions of the mother, e.g. autoimmune diseases.

Due to the large number of SD, symptoms, diagnosis and therapy differ widely. However, abnormal development of cartilage and bone does often result in retarded growth, short stature or even dwarfism. Distinct elements of the skeleton may grow disproportionally and may not develop into their physiological shape. Thus, orthopedic problems are the most common consequences of SD, but the disease may affect other organ systems such as the cardiovascular system, the CNS and the sense organs. SD develops in the course of life and may affect intrauterine organ development, growth in childhood and adolescence or even tissue aging.

Diagnosis is usually based on medical history, clinical and radiographic examination as well as molecular biologic diagnostics. Pharmacological and surgical treatment may help to improve the patient's quality of life if he or she is suffering from specific forms of SD.

Patient Information

The term skeletal dysplasia (SD) comprises several hundred diseases that affect cartilage and bone development and growth. They are associated with distinct deformities, disproportional growth and short stature. Further symptoms depend on the specific SD and may vary from limited mobility, poor posture and pain to respiratory, neurologic and cardiac disorders. SD may result from genetic defects, exposure to toxins during pregnancy or even certain diseases the child's mother may be suffering from.

Since SD affects skeleton development and growth, it is usually diagnosed prenatally or in early childhood. Routine examinations during pregnancy and infancy are of utmost importance to detect possible alterations in cartilage or bone early. This way, parents are able to consult with medical care givers and to make the corresponding decisions regarding pregnancy, delivery and lifestyle of the child.

Alterations detected in ultrasound or X-ray examinations usually prompt further analyses to corroborate the suspected diagnosis and to determine the specific SD. Molecular biologic diagnostics may be necessary to do so. Only after an exact diagnosis has been established, a prognosis regarding the child's life expectancy and quality of life can be made. Some forms of SD are lethal, and to those patients suffering from non-lethal SD, only supportive treatment can be offered.

Among the most common forms of SD are achondrogenesis, thanatophoric dysplasia, achondroplasia and osteogenesis imperfecta (colloquially called "brittle bone disease").



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Last updated: 2019-07-11 21:24