A  20 year old patient was investigated for a genetic disease.  There is gain-of-function mutation

in the FGF receptor 3 (FGFR3). The elder brother and sister are also affected by the same disease.  Which of the following findings will be obvious in this patient? 

1. Brittle bone disease
2. Ectopic lens
3. Fusion of the digits
4. Rhizomelic shortening of the limbs
5. Underdeveloped thoracic cavity

 

 

 

 

 

Answer:d

Explanation:

Achondroplasia is caused by gain-of-function point mutations in the FGF receptor 3 (FGFR3). Normally, FGF-mediated activation of FGFR3 inhibits endochondral growth.  Activation of FGFR3 exaggerates this effect, suppressing growth. Approximately 90% of cases stem from new mutations in the paternal allele.  There is rhizomelic shortening of the limbs.

 

 (Choice a) Brittle bone disease is Osteogenesis imperfect. The fundamental abnormality in Osteogenesis Imperfecta is too little bone, resulting in extreme skeletal fragility. Other findings include blue sclerae caused by decreased collagen content, making the sclera translucent and allowing partial visualization

of the underlying choroid; hearing loss related to both a sensorineural deficit and impeded conduction due to abnormalities in the bones of the middle and inner ear; and dental imperfections (small, misshapen, and blueyellow teeth) secondary to a deficiency in dentin.

 

(Choice b) Ectopic lens is found in Marfans Syndrome.

(Choice c) Fusion of digits can occur as an isolated feature.

(Choice e) Underdeveloped thoracic cavity is found in Thanatophoric dysplasia  which is the most common lethal form of dwarfism, affecting about 1 in every 20,000 live births. The patients have micromelic shortening of the limbs, frontal bossing, relative macrocephaly, a small chest cavity, and a bell-shaped abdomen. The underdeveloped thoracic cavity leads to respiratory insufficiency,

and these individuals frequently die at birth or soon after.

 

Educational Objective:

Achondroplasia is one of the most common skeletal dysplasia.  It is the major cause of dwarfism. It is an autosomal dominant inheritance.  The cartilage growth is disturbed.  Patients have shortened proximal extremities, a trunk of relatively normal length, and an enlarged head with bulging forehead and conspicuous depression of the root of the nose. The longevity, intelligence, or reproductive status is normal.