Thanatophoric Dysplasia: Causes, Symptoms, Treatment

Introduction

Defining Thanatophoric Dysplasia

Thanatophoric Dysplasia is a form of severe skeletal disorder characterized by very notably short limbs and redundant skin on the person's arms and legs. Additional features of the condition include short ribs, a narrowing of the person's chest, enlargement of the person's head, underdeveloped lungs, and prominent and wide-spaced eyes. The term 'thanatophoric is Greek and means 'death bearing.' Infants with thanatophoric dysplasia are often stillborn or perish shortly after birth due to respiratory failure. There are, however, a few people who survive into childhood with extensive medical assistance.

The U.S. Social Security Administration (SSA) has included Thanatophoric Dysplasia, Type 1 as a Compassionate Allowance to expedite a disability claim.

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Thanatophoric dysplasia occurs in approximately one in every twenty-to-fifty thousand newborns. Medical researchers have described two major forms of the condition; Type I and II.

• Type I thanatophoric dysplasia is marked by the presence of thigh bone curvature and a flattening of the person's spine bones, referred to as 'platyspondyly.'
• Type II thanatophoric dysplasia is marked by straight thigh bones and a moderate to severe abnormality of the person's skull, referred to as a 'cloverleaf skull.'

Causes of Thanatophoric Dysplasia

Type I and II thanatophoric Dysplasia are caused by mutations in the FGFR3 gene. The gene provides instructions for producing a protein for developing and maintaining a person's brain tissue and bone. Mutations in the FGFR3 gene cause the protein to become over-active, leading to severe disturbances in the person's bone growth, characteristic of the condition. Medical science does not know how mutations to the FGFR3 gene cause abnormalities related to the condition and a person's skin and brain.

Thanatophoric dysplasia is considered by the medical community to be a form of autosomal dominant disorder because one mutated copy of the FGFR3 gene in each person's cells is enough to cause the condition. Nearly every person with thanatophoric dysplasia has the disorder due to new mutations in the FGFR3 gene; it happens in people with no history of the disorder in their family. No people with thanatophoric dysplasia are known to have had children. The disorder must therefore have not been passed between generations. The names also know as thanatophoric dysplasia:

• Dwarf, thanatophoric
• Thanatophoric dwarfism
• Thanatophoric short stature

Symptoms of Thanatophoric Dysplasia

Unfortunately, newborns with thanatophoric dysplasia are often stillborn or die shortly after birth. Death in the neonatal period is often due to severe respiratory distress caused by a reduced thoracic capacity and Hypoplastic lungs or respiratory failure caused by brain stem compression. There are some rare reports of newborns with thanatophoric dysplasia surviving into early childhood. Female and male newborns are affected equally by the condition. Additional symptoms of thanatophoric dysplasia include:

• Protuberant abdomen
• Generalized hypotonia
• Severe growth deficiency
• Narrow, bell-shaped thorax with short ribs
• Brachydactyly with a trident hand configuration
• Flat faces with low nasal bridge and proptosis eyes
• Macrocephalic head with frontal bossing and large anterior fontanel
• Cloverleaf-shaped skull due to premature closure of the cranial sutures
• Marked bilateral shortening of the limbs (micromelia) with redundant skin folds

Diagnosing Thanatophoric Dysplasia

The types of thanatophoric dysplasia may be diagnosed by the features each type presents. For example, the appearance of either curved or straight bones in the person indicates the disorder. Thanatophoric dysplasia type I is the more common of the two types and is characterized by an average-shaped skull and long curved bones, with the person's femur being the most affected. Thanatophoric dysplasia type II is associated with the presence of a cloverleaf-shaped skull and straight femurs. This is the observation of clinical overlap between the two subtypes.

The pathophysiology of thanatophoric dysplasia is notable. FGFR3 is a part of the tyrosine kinase receptor family. Usually, FGFR3 is a negative regulator of bone growth. Mutations in thanatophoric dysplasia that code for FGFR3 cause a gain in function, sending negative signals to the person's cartilage cells. This happens when ligand binding within the chondrocytes induces receptor homodimerization and heterodimerization. This, in turn, activates tyrosine kinase function, which then potentiates several effects on the person's cell growth and differentiation.

Medical researchers suggest that mutations in FGFR3 lead to cysteine residues forming disulfide bonds between extracellular domains of mutant monomers. Activation of the homodimer receptor complex increases its stability, promoting translocation of the complex into the nucleus, which can interfere with terminal chondrocyte differentiation. Because of this, generalized disorganization of Endometrial ossification at the person's bone growth plate occurs, something that is readily identifiable.

Most people who experience severe fetal skeletal dysplasia may achieve a prenatal diagnosis through ultrasonography during the second or third trimester of pregnancy. Unfortunately, diagnosing thanatophoric dysplasia using only ultrasonography can be difficult. The key findings of ultrasonography include:

• Micromelia
• Bowed femurs
• Macrocephaly
• Polyhydramnios
• Ventriculomegaly
• Cloverleaf-shaped skull
• Well-ossified skull and spine
• Platyspondyly of the vertebrae
• Narrow chest cavity with shortened ribs
• Growth deficiency with limb length of less than 5%

A chromosome analysis and molecular testing for FGFR3 with targeted and sequence mutation analysis can help diagnose thanatophoric dysplasia. Two-dimensional ultrasonography can reveal polyhydramnios, ventriculomegaly, growth deficiency, narrowing of the person's thorax, micromelia, and flattening of the person's vertebrae. Three-dimensional ultrasonography can reveal scapular anomalies, the fetal face, and chest hyperplasia.

Postnatal radiographs and additional imaging studies may reveal irregular metaphyses of the person's long bones and rhizomelic shortening of bones. These studies can also reveal platyspondyly, wide intervertebral spacing, skull enlargement and a small foramen magnum, brain stem compression, hydrocephalus, temporal lobe malformations, brainstem hypoplasia, or neuronal migration abnormalities. Histologic evaluation of the person's long bone structure can show disruption of endochondral ossification.

Treatment of Thanatophoric Dysplasia

Inpatient care is needed for newborns with thanatophoric dysplasia. Intubation may be needed as a form of aggressive treatment for respiratory distress; admission to a neonatal unit is required. If aggressive treatment is deferred, palliative treatment consists of keeping the newborn comfortable, warm, and nourished. At this time, medication therapy is not a part of the care provided in association with thanatophoric dysplasia directly. However, medications might be indicated for treating concurrent medical conditions associated with the disorder.

Author Credentials:

Thomas C. Weiss is a researcher and editor for Disabled World. Thomas attended college and university courses earning a Masters, Bachelors and two Associate degrees, as well as pursing Disability Studies. As a Nursing Assistant Thomas has assisted people from a variety of racial, religious, gender, class, and age groups by providing care for people with all forms of disabilities from Multiple Sclerosis to Parkinson's; para and quadriplegia to Spina Bifida. Explore Thomas' complete biography for comprehensive insights into his background, expertise, and accomplishments.

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Cite This Page (APA): Weiss, T. C. (2010, April 3 - Last revised: 2023, February 1). Thanatophoric Dysplasia: Causes, Symptoms, Treatment. Disabled World. Retrieved September 20, 2024 from www.disabled-world.com/disability/types/thanatophoric-dysplasia.php

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