Hutchinson-Gilford progeria syndrome (HGPS)

-

What is progeria?

It is also known as Hutchinson-Gilford progeria syndrome (HGPS).It is a rare, fatal, disorder characterized by  segmental premature aging disease

What is the pattern of inheritance?

Autosomal Dominant

What causes this disorder?

LMNA gene single base mutation  results in the production of a mutant lamin A protein called progerin . 

Lamin A is an intermediate filament inner nuclear membrane protein found in most differentiated cells of the body.

What are the clinical features?

Children develop the appearance of accelerated aging, but both clinical and biologic overlaps with aging are segmental, or partial. 

Physical appearance changes dramatically each year that they age

What is the effect on IQ?

Normal 

Which organs are not affected by progeria?

Liver
Kidney 
GIT
Thyroid
Immune
CNS(except for stroke)

What are the ophthalmic effects?

exposure keratopathy 

What is the effect on hearing?

Low-tone conductive hearing loss is pervasive in progeria and indicative of a stiff tympanic membrane and/or deficits in the middle ear bony and ligamentous structures.

What are the CVS effects?

Approximately 80% of progeria deaths are caused by heart failure, possibly precipitated by events such as superimposed respiratory infection or surgical intervention. 

Progeria is a primary vasculopathy characterized by pervasive accelerated vascular stiffening, followed by large- and small-vessel occlusive disease from atherosclerotic plaque formation, with valvular and cardiac insufficiency in later years.

Risk of stroke 

Poor sexual development

What are the characteristic laboratory features?

Low serum leptin (>90% of cases)
Insulin resistance (60% cases)
relatively high platelet

Normal lipid panels, normal RFT,LFT

What are other senile syndromes?

Wiedemann-Rautenstrauch syndrome
Restrictive dermatopathy
Werner syndrome
Cockyane syndrome
Rothmung thompson 
Nester Guillermo progeria syndrome.


What are the treatment options ?


Growth hormone supplementation
Aspirin 

Inhibitor of posttranslational farnesylation of progerin -- Lonafarnib

Ongoing trial of Lonafarnib and everolimus

Trial of lonafarnib with provastatin (to lower cholesterol) and zoledronate(for osteoporosis) resultes in no benefits.

Comments

Post a Comment

Popular posts from this blog

Congenital Hypertrophic Pyloric Stenosis

-
Image
What are the parts of pylorus? The incisura angularis divides the stomach into a body to the left and a pyloric portion to the right. The sulcus intermedius further divides the pyloric portion of the stomach: the pyloric vestibule to the left, denoted by an outward convexity of the greater curvature. The pyloric antrum or pyloric canal to the right The pyloric antrum is 2.5 cm and terminates in pyloric orifice into duodenum.   What happens to the normal anatomical structural in CHPS? In infants with IHPS, the pyloric ring is no longer identifiable as a clearly definable separation between the normally distensible pyloric antrum and the duodenal cap. Instead, a channel of variable length (1.5–2.0 cm) corresponding to the pyloric canal separates the normally distensible portion of the antrum from the duodenal cap. ·          Infantile hypertrophic pyloric stenosis  was first fully described by  Harald Hirschsprung  i...
Read more

HYPOTHYROIDISM CLINICAL FEATURES

-
Image
     1.       What are the clinical features of congenital hypothyroidism in a newborn? The clinical manifestations are commonly subtle in newborns with congenital hypothyroidism (CH).   Newborns with CH may be asymptomatic because of presence of maternal T 4 (which contributes to approximately one-third of circulating T 4 in a newborn) and residual functioning thyroid tissue.   FEATURES AT BIRTH   The classical symptoms of congenital hypothyroidism include ·          lethargy, ·          hoarse cry, ·          feeding difficulty, ·          constipation not responding to treatment, and increased somnolence.   The characteristic signs of CH include ·          Prolonged neonatal jaundice, ·   ...
Read more

Febrile Seizure: Review

-
Image
Febrile Seizures   What is febrile seizure? Febrile seizures are seizures that are caused by a sudden spike in body temperature with fevers greater than 38C or 100.4F, with no other underlying seizure-provoking causes or diseases such as the central nervous system (CNS) infections, electrolyte abnormalities, drug withdrawal, trauma, genetic predisposition or known epilepsy. There shouldn't be any prior history of afebrile seizure as in such case the fever might be the cause of breakthrough seizure. however , there are no consensus regarding inclusion or exclusion of children with neurodevelopment disorder such as Autism spectrum disorder which has the predisposition to seizures. Age of presentation: As per American academy of Pediatrics: 6 months to 5 years (however cases unto 7 years of age have been diagnosed as FS) As per earlier definition ILAE - infant up to age of 1 month can be diagnosed as FS. As per NIH (National Institute of Health) children between 3 months and 5 years ...
Read more