Genetics of  Prader Willi Syndrome

 Table of contents:

Introduction:

Nature of Prader Willi Syndrome:

Etiology and Pathogenesis:

Genetics of Prader Willi Syndrome

Animal Model

Diagnostic Criteria

Case Study

Management

Conclusion

Genetics of  Prader Willi Syndrome

Diagnostic Criteria:

Differential Diagnosis: In this part of diagnosis PWS and its hypotonia compared and separated from other infantile hyptonias. The basis of separation includes congenital myotonic dystrophy, Zellweger’s Syndrome, Atonic diplegia, spinal muscle atrophy, congenital myopathies, benign congenital hypotonias and in some cases CNS anoxia. These are helpful in diagnosis of stature and muscle tone, strength and mass, reflexes, oral motor mechanism, and general CNS.

Consensus Diagnosis: It has been developed by a group of national and international experts based on 113 patients (Holm et al., 1993). They recommended three criteria to diagnose PWS and those are as follows: (1)

·        Major Criteria

·        Minor Criteria

·        Supportive Findings

Major criteria:

1.      Neonatal and infantile central hypotonia with poor suck, gradually improving with age.

2.      Feeding problems in infancy with need for special finding techniques and poor weight gain/failure to thrive.

3.      Excessive or rapid weight gain or weight-for-length chart after 12 months but before 6 years of age; central obesity in the absence of intervention.

4.      Characteristic facial feature.

5.      Hypogonadism

6.      Global development delay in a child younger than 6 years of age; mild to moderate mental retardation of learning problems in older children.

7.      Hyperphagia

8.      Deletion of 15(q11-q13).

Minor criteria:

1.      Decrease fetal movement improving with age.

2.      Characteristic behavior problems.

3.      Sleep disturbance or Sleep apnea.

4.      Short stature.

5.      Hypopigmentation.

6.      Small hands (<25^th percentile) and facts (<10^th percentile)

7.      Narrow hands with straight ulnar* border.

8.      Eye abnormalities.

9.      Thick viscous saliva with crusting at corners of the mouth.

10.  Speech articulation defect.

11.  Skin picking.

Supportive findings:

1.      High pain threshold.

2.      Decreased vomiting.

3.      Temperature instability.

4.      Scoliosis and/or kipsies.

5.      Early demarche.

6.      Osteoporosis.

7.      Unusual skill with jigsaw puzzles.

8.      Normal neuromuscular studies

Other basis of diagnosis:

White* et al. (1996): They exploited allele specific replication differences in imprinted regions for detection of unapparent dismay. To distinguish Angelman Syndrome and PWS uniparental disomy they used FISH of D15S9 and SNRPN. They noted recurrence is at high risk when the child has de novo uniparental disomy and may be 50% with biparental inheritance.

Kubota at al. (1996): They reported that FISH or UPD were not as efficient as the initial screening test, methylation analysis has the advantage of detecting all classes of molecular defects in PWS cases. They emphasized on the conventional cytogenetic analysis in parallel with DNA methylation. They noted some cases of PWS with balanced translocation or distal to SNRPN and normal methylation.