PEDIATRIC DENTISTRY/Copyright ]989 byThe American Academy of Pediatric Dentistry

Volume 11, Number 2

Rett syndromema rare and often misdiagnosedsyndrome: case reportMichael A. Buccino, DDS, MSD James A. Weddell, DDS, MSD

Abstract

Rett syndrome is a recently discovered, progressiveneurological disorder that occurs exclusively in females earlyin life. Females with this rare and often misdiagnosed clinicalentity have unusual but distinctive oral~digital habits.Dentists aware of Rett syndrome and its distinctmanifestations will be able to aid in early diagnosis andtreatment of those afflicted.

A case report of a 4-year, 3-month-old white female withRett syndrome and review of pertinent literature arepresen ted. The previously reported oral~digital habits and oralmanifestations of Rett syndrome are listed along with otherunreported oral findings. Many of these oral manifestationsare not unique to Rett syndrome. There is a likelihood that theymay be related to trauma secondary to the excessive oral/digital habits, poor gait, and seizure activity.

Rett syndrome is a progressive neurologicaldisorder that occurs exclusively in females and ischaracterized by normal early development followedby a progressive loss of acquired functions.

The purpose of this paper was to review this raresyndrome and increase awareness of the syndromesmanifestations among dental professionals, therebyaiding early diagnosis and treatment.

A case report of a 4-year, 3-month-old white femalewith Rett syndrome and review of pertinent literatureare presented. The previously reported oral/digitalhabits and oral manifestations of Rett syndrome arelisted along with other unreported oral findings.

The International Retts Syndrome Association hasnoted that Rett syndrome often is misdiagnosedbecause there appears to be a lack of awareness of thesyndrome by the professional.

Literature Review

Diagnostic Criteria and Characteristic FeaturesRett syndrome first was described by Rett (1966).

reported a progressive neurological disorder thatoccurred exclusively in girls and which had its onset

near the end of the first year of life or during the first 6months of the second year of life. Characteristic featuresincluded autistic behavior, dementia, apraxia of gait,loss of facial expression, and stereotyped use of thehands.

Leiber and Olbrich (1972) first described thiscondition in detail in their catalog of syndromes as "Rettsyndrome." Hagberg et al. (1983) brought the syndrometo the attention of neurologists worldwide when theydescribed 35 cases from Sweden, France, and Portugalwith a uniform and striking progressiveencephalopathy. Hagberg (1985) published the firstdiagnostic criteria for Rett syndrome (Table 1).

One year later, A1-Mateen et al. (1986) summarizedthe characteristics of Rett syndrome into 3 phases (Table2, next page) and reinforced the previous findings ofRett (1966) and Hagberg et al. (1983). They identified 2 previously unreported features of Rettsyndrome: an extrapyramidal disorder and lacticacidemia.

The first recognized cases of Rett syndrome in theUnited States were reported by Holm in 1985. Murphy

TABLE 1. Rett Syndrome: Diagnostic Criteria forInclusion

1. Sex - Female2. Normal prenatal and perinatal period - Essentially normal psy-

chomotor development through the first 6, often 12-18 monthsof life

3. Normal head circumference at birth - Deceleration of head growth(and therefore, by inference, brain growth) between ages months-4 years.

4. Early behavioral, social, and psychomotor regression - Loss ofachieved abilities, evolving communication dysfunction, de-mentia

5. Loss of acquired purposeful hand skill - Through ages 1-4 years6. Hand wringing-clapping-"washing hand" stereotypes - Appearing

between ages 1-4 years7. Appearance - Gait apraxia and truncal apraxia/ataxia appearing

between ages 1-4 years8. Diagnosis - Tentative until 3-5 years of age.

(Hagberg et al. 1985)

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TABLE 2. Characteristic Features of Rett Syndrome

First Phase

Stagnation of development acquisitions (4-18 months of age) Insidious, occasionally acute, regression (18-36 months of age) Impairment or loss of speech Autistic behavior with distinctive hand movements (hand-wash-

ing automatism) Frequent hyperventilation

Second Phase

Minor motor seizures (onset at 24 years of age) Loss of purposeful use of extremities (apraxia) Extrapyramidal symptoms (choreoathetosis and dystonia in 50%

of cases)

Chronic Phase

Progressive muscle wasting and spasticity Plateau of head circumference (as early as 1 year of age) Plateau of weight and usually height (after 10 years of age)

(A1-Mateen et al. 1986)

et al. (1986) stated that Rett syndrome: has beenidentified in 4 of the 7 continents; is seen across all social,religious, and ethnic groups; and has eluded all effortsto unravel its suggested genetic cause. Budden (1986)wrote that individuals with Rett syndrome frequentlyhave been misdiagnosed as having mental retardation,cerebral palsy, and, most commonly, autism. Hagbergand Witt-Engerstrom (1986) stated that Rett syndromecan be misdiagnosed as infantile autism, childhoodpsychosis, spinocerebellar degeneration, neuraxonaldystrophy, hypotonic or ataxic cerebral palsy, minormotor epilepsy, toxic encephalitic process, infantileceroid lipofuscinosis, phenylketonuria, tuberoussclerosis, mental retardation, heredoataxias, orleukodystrophies.

Important clinical criteria that aid in the syndromesdiagnosis include autism, loss of hand use andlanguage. The most frequent misdiagnosis of Rettsyndrome is infantile autism (Budden 1966). Kerr andStephenson (1985) recommend that Rett syndromeshould be considered whenever girls are referred witha diagnosis of autism. Naidu (1986) concludes that theloss of hand use and language before the age of 2 yearsare the most outstanding early clinical indices ofsuspicion.

Other clinical findings in children with Rettsyndrome include: a shift from left-handedness toright-handedness near age 7 (Nomura et al. 1984; Olssonand Rett 1986); a possible defect in the specialized unitsof the inferior colliculus or higher auditory centerswhich subserve frequency sweep discrimination (Lennet al. 1986); self-injurious hand biting (Iwata et al. 1986);stereotypic hand washing; apnea during activewakefulness, causing episodes of severe cerebral

hypoxia (Cirignotta et al. 1986); and an abnormalelectroencephalogram (EEG) portraying rhythmicalslowing (Niedermeyer et al. 1986).

Olsson and Rett (1987) speculate that thecharacteristic hand washing stereotypies are due to aregression of acquired cognitive skills to the fourthstage of sensorimotor intelligence as described byPiaget (1952). These automatisms are a result of severemental and motor regression and fulfill Piagetsdescription of primary circular reactions. Lenn (1986)felt that the stereotypic hand washing is mostsuggestive of involvement of the basal ganglia.

Etiology and PathogenesisThe etiology of Rett syndrome is unknown

(Bachmann et al. 1986; Harris et al. 1986; Nomura andSegawa 1986). Rett (1966) originally attributed disorder to hyperammonemia, but this symptom is nolonger essential in the diagnosis. The conditionresembles a metabolic disorder; however, laboratoryand metabolic studies have revealed inconsistentresults.

During Rett syndromes 23-year-old history, manyother possible etiologies have been theorized. Holm(1985) speculated that the syndromes etiology may a new mutation caused by the environment. Hagberg etal. (1983) speculate that the disorder is caused by dominant mutation on an X chromosome, which islethal in males.

Another hypothesis of the pathogenesis of Rettsyndrome suggests that symptoms result from anabnormality in the dopamine system, a neuro-transmitter system which regulates the control ofvoluntary movements in the extrapyramidal system(Harris et al. 1986). Nomura et alo (1985) speculate that Rett syndrome progresses, the dopamine systembecomes hyperactive due to postsynaptic super-sensitivity caused by hypoactive dopamine neurons.

Nomura and Segawa (1986) have clinical andpolysomnographic data that support the hypothesisthat Rett syndrome is due to a disorder of thenoradrenergic, serononergic, and dopaminergicsystems arising in the locus ceruleus, raphe nuclei, andsubstantia nigra, respectively.

The incidence of the condition is approximately I in15,000 live female births (Kerr and Stephenson 1985;Hagberg 1985). Budden (1986) diagnosed 13 caseswithin a 9-month period and therefore suggests that thefrequency of the disorder is higher. Moser (1986) statedthere have been approximately 605 "classic" cases ofRett syndrome reported in the world, and of these,approximately 190 have been diagnosed in the UnitedStates. Life span appears to be unaffected although lifetables have not yet been established; however, the

152 Rett Syndrome--Case Report: Buccino and Weddell

pathogenesis of this syndrome is progressive (Naidu etal. 1986).

Treatment

Treatment of the syndrome includes physical andoccupational therapy to develop and maintain muscletone, function, and contact (Hanks 1986). Music therapyhas been used to lengthen attention span (Hanks 1986;Wesecky 1986). Various medications (ethosuximide,clonazepam, metharbital, ACTH, ketogenic diet,phenobarbital, phenytoin, clorazepate, valproate, andespecially carbamazepine) have been prescribed forseizure control (Budden 1986; Haas et al. 1986;Philippart 1986).

Oral ManifestationsThe oral manifestations of Rett syndrome have been

reported only in the medical literature. The previouslyreported oral manifestations and oral/digital habitsinclude: bruxism, drooling, h