Praderwilli Syndrome

The criteria for a diagnosis of Prader-Willi syndrome (PWS) are based on a phenotypic scoring system, but incorporate genetic data. Because infants and young children have fewer symptoms than older children and adults with PWS, the scoring system differs by age group. The revised 2001 diagnostic criteria are presented in Tables 25 and 26, and have supplanted the similar 1993 system of Holm et al. Table 26 gives guidelines as to when to perform DNA testing for PWS.

RETT'S SYNDROME

Rett's syndrome (RS) has often been classified among the autistic spectrum disorders. (See "Autism Spectrum Disorders" section in Chapter 3 for alternative diagnostic criteria.) Great progress has been

Table 25

Diagnostic Criteria for Prader-Willi Syndrome Major criteria

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

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

3. Excessive or rapid weight gain on weight-for-length chart (excessive is defined as crossing two centile channels) after 12 months but before 6 years of age; central obesity in the absence of intervention.

4. Characteristic facial features with dolichocephaly in infancy, narrow face or bifrontal diameter, almond-shaped eyes, small appearing mouth with thin upper lip, down-turned corners of the mouth (three or more symptoms are required).

5. Hypogonadism—with any of the following, depending on age:

a. Genital hypoplasia, (male: scrotal hypoplasia, cryptorchidism, small penis and/or testes for age [<5th percentile]; female: absence or severe hypoplasia or labia minora and/or clitoris).

b. Delayed or incomplete gonadal maturation with delayed pubertal signs in the absence of intervention after 16 years of age (male: small gonads, decreased facial and body hair, lack of voice change; female: amenorrhea/oligomenorrhea after age 16).

6. Global developmental delay in a child <6 years of age; mild-to-moderate mental retardation or learning problems in older children.

7. Hyperphagia/food foraging/obsession with food.

8. Deletion of chromosome 15q11-13 on high resolution (>650 bands) or other cytogenetic molecular abnormality of the Prader-Willi chromosome region, including maternal disomy.

Minor criteria

1. Decreased fetal movement or infantile lethargy or weak cry in infancy, improving with age.

2. Characteristic behavior problems—temper tantrums, violent outbursts, and obsessive-compulsive behavior; tendency to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn; perseverating, stealing, and lying (five or more of these symptoms required).

3. Sleep disturbance and sleep apnea.

4. Short stature for genetic background by age 15 (in the absence of growth hormone intervention).

5. Hypopigmentation—fair skin and hair compared with family.

6. Small hands (<25th percentile) and/or feet (<10th percentile) for height age.

7. Narrow hands with straight ulnar borders.

8. Eye abnormalities (esotropia, myopia).

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

10. Speech articulation defects.

11. Skin picking. Supportive findings

1. High pain threshold.

2. Decreased vomiting.

3. Temperature instability in infancy or altered temperature sensitivity in older children and adults.

4. Scoliosis and/or kyphosis.

5. Early adrenarche.

6. Osteoporosis.

7. Unusual skill with jigsaw puzzles.

8. Normal neuromuscular studies.

To score, major criteria are weighted at 1 point each, and minor criteria are weighted at 1/2 point each. Supportive findings increase the certainty of diagnosis but are not scored. For children 3 years of age or younger, 5 points are required, 4 of which should come from the major group. For children older than 3 years of age and for adults, a total score of 8 is required and major criteria must comprise 5 or more points of the total score.

Adapted with permission from Gunay-Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB. The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 2001;108:92, and from the American Academy of Pediatrics.

Table 26

Criteria to Prompt DNA Testing for Prader-Willi Syndrome

Age at assessment features sufficient to prompt DNA testing

A. Birth-2 years

1. Hypotonia with poor suck.

1. Hypotonia with history of poor suck.

2. Global developmental delay.

1. History of hypotonia with poor suck (hypotonia often persists).

2. Global developmental delay.

3. Excessive eating (hyperphagia, obsession with food) with central obesity if uncontrolled.

D. 13 years through adulthood

1. Cognitive impairment; usually mild mental retardation.

2. Excessive eating (hyperphagia, obsession with food) with central obesity if uncontrolled.

3. Hypothalamic hypogonadism and/or typical behavior problems (including temper tantrums and obsessive-compulsive features).

Adapted with permission from Gunay-Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB. The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics 2001;108:92, and from the American Academy of Pediatrics.

made in unraveling the molecular and genetic basis of RS, leading to its inclusion here as a genetic disorder. Based on current molecular biological information, RS should be viewed as a neuro-developmental disorder instead of a degenerative disorder. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are the molecular basis for more than 80% of girls fulfilling criteria for classic RS.

In September 2001, the International Rett's Syndrome Association convened a panel of international experts, with the aim to establish as simple a dataset as possible to assist physicians in making the clinical diagnosis of RS. The meeting resulted in an updated set of diagnostic/clinical criteria based on observations and knowledge gained from understanding the natural history of RS, and from new information based on the discovery of the MECP2 gene. The new criteria include information on atypical or borderline variants of RS, which is important for increasing physician awareness and for expanded understanding of RS.

It is important to emphasize that at our present level of knowledge, the diagnosis of RS remains a clinical one, and is not made solely based on MECP2 mutations. RS can occur with or without mutations in MECP2, and MECP2 mutations can occur without the diagnosis of RS. Therefore, consensus on the diagnostic criteria for classic and variant forms of RS is essential, and these criteria must be applied consistently for the accuracy of phenotype-genotype correlation studies (Tables 27 and 28).

Table 27

Diagnostic Criteria for Rett's Syndrome

Necessary criteria

1. Apparently normal prenatal and perinatal history.

2. Psychomotor development largely normal through the first six months or may be delayed from birth.

3. Normal head circumference at birth.

4. Postnatal deceleration of head growth in the majority.

5. Loss of achieved purposeful hand skill between ages 6 months and 2.5 years.

6. Stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing, and washing/ rubbing automatisms.

7. Emerging social withdrawal, communication dysfunction, loss of learned words, and cognitive impairment.

8. Impaired (dyspraxic) or failing locomotion. Supportive criteria

1. Awake disturbances of breathing (hyperventilation, breath-holding, forced expulsion of air or saliva, air swallowing).

2. Bruxism.

3. Impaired sleep pattern from early infancy.

4. Abnormal muscle tone successively associated with muscle wasting and dystonia.

5. Peripheral vasomotor disturbances.

6. Scoliosis/kyphosis progressing through childhood.

7. Growth retardation.

8. Hypotrophic small and cold feet; small, thin hands. Exclusion criteria

1. Organomegaly or other signs of storage disease.

2. Retinopathy, optic atrophy, or cataract.

3. Evidence of perinatal or postnatal brain damage.

4. Existence of identifiable metabolic or other progressive neurological disorder.

5. Acquired neurological disorder resulting from severe infections or head trauma.

Adapted with permission from Hagberg B, Hanefeld F, Percy A, Skjeldal O. An update on clinically applicable diagnostic criteria in Rett syndrome. Eur J Pediatr Neurol 2002;6:293-297, and from Elsevier.

Table 28

Revised Delineation of Variant Phenotypes of Rett's Syndrome

Inclusion criteria

1. Meet at least three main criteria.

2. Meet at least five supportive criteria. Six main criteria

1. Absence or reduction of hand skills.

2. Reduction or loss of babble speech.

3. Monotonous pattern to hand stereotypies.

4. Reduction or loss of communication skills.

5. Deceleraton of head growth from first years of life.

6. Rett's syndrome disease profile: a regression stage followed by a recovery of interaction contrasting with slow neuromotor regression.

Eleven supportive criteria

1. Breathing irregularities.

2. Bloating/air swallowing.

3. Teeth grinding, harsh-sounding type.

4. Abnormal locomotion.

5. Scoliosis/kyphosis.

6. Lower limb amyotrophy.

7. Cold, purplish feet, usually growth-impaired.

8. Sleep disturbances including night screaming outbursts.

9. Laughing/screaming spells.

10. Diminished response to pain.

11. Intense eye contact/eye pointing.

Adapted with permission from Hagberg B, Hanefeld F, Percy A, Skjeldal O. An update on clinically applicable diagnostic criteria in Rett syndrome. Eur J Pediatr Neurol 2002;6:293-297, and from Elsevier.

Proposed Diagnostic Criteria for Schwannomatosis

Definite

Possible

Age over 30 years, two or more non-intradermal schwannomas, at least one with histological confirmation, no evidence of vestibular tumor on high-quality MRI scan, and no known constitutional NF2 mutation

Natural Weight Loss

Natural Weight Loss

I already know two things about you. You are an intelligent person who has a weighty problem. I know that you are intelligent because you are seeking help to solve your problem and that is always the second step to solving a problem. The first one is acknowledging that there is, in fact, a problem that needs to be solved.

Get My Free Ebook


Post a comment