Recent experience with Rett syndrome at a tertiary care center
S. Kumar, M. Alexander, C. Gnanamuthu
Department of Neurological Sciences, Christian Medical College, Vellore - 632004, India.
Rett syndrome (RS), a neurological developmental disor- and Witt-Engerstrom.6 The clinical characteristics are summarized
in Table 1. All children had uneventful antenatal and perinatal peri-
der, is one of the commonest causes of cognitive impair-
ods and a period of normal development, ranging from the first seven
ment in girls and women. These patients are often initially
to 18 months. During the period of normal development, three chil-
misdiagnosed as idiopathic mental retardation, cerebral dren were able to walk without support. They also attained a vo-
palsy, or autism. Despite several reports from the West, there cabulary of 8-10 words. Family history was negative in all.
are very few reports from the Indian population. We present Later in the course of illness, the complaints were an inability to
four female children with RS and emphasize the importance use hands for purposeful movements, social withdrawal, problems
of early diagnosis. with communication and regression of acquired motor and language
skills. They had marked communication problems and the vocabu-
Key Words: Rett syndrome, Mental retardation, Clinical di-
lary regressed to one-two words in three children and four-six words
agnosis. in one. They had difficulty in comprehending spoken language but
could respond to loud noise and bright light. Stereotypic hand move-
ments were noted in all the children. The stereotypic movements
included beating hands on the abdomen in one (Case 1), repeated
Introduction closing and opening of hands in one (Case 2), slapping own face with
hands and wringing movements in one (Case 3) and repeated inap-
propriate hand clapping in one (Case 4). Gait problems, apraxia,
Rett syndrome (RS), one of the commonest causes of pro-
was noted in all the children. One child (Case 1) had mild swaying to
found cognitive impairment in girls and women, was first rec- either side, whereas 2 children (Cases 2 and 3) had broad-based
ognized in the 1960s and the first report form India was in unsteady gait with repeated falls. One child (Case 4) had an unusual
1994.1 Though RS has a prevalence of 1 per 10000 to 1 per way of turning to one side before getting up from the squatting posi-
22000,2 in India it is confined to very few case reports.3-4 Prob- tion to avoid falling. Side-to-side ‘rocking’ was seen in two children
ably, this may be related to underdiagnosis of the condition or (Cases 1 and 2). All children had cognitive impairment and had no
misdiagnosis of these children as cerebral palsy1 or autism. bowel and bladder control. Two patients had history of seizures. One
The current report summarizes our recent experience with child (Case 1) had myoclonic jerks whereas another child (Case 4)
had generalized tonic-clonic seizures. Two patients had bruxism. One
RS and discusses the clinical diagnosis.
patient had hearing loss.
Three children (Cases 1, 2, and 3) had microcephaly. Weight and
Case Report height were below the 50th percentile in all the four children. None
had any dysmorphic features. Muscle wasting and hypotonia was
Retrospective review of the case records of inpatients in the neu- noted in one child and one child had spasticity.
rology wards during the period 2001-2002, identified four female Brain CT was normal in three children, in Case 2 MRI showed
children with RS. The mean age at presentation was 33 months (23- frontal lobe atrophy and thinning of the anterior corpus callosum.
42 months). Diagnosis was based on the criteria proposed by Hagberg EEG was abnormal in all the four children (multifocal epileptiform
Table I: Clinical characteristics of patients with Rett syndrome in our series
Sr. No. Age Normal development Small head Stereotypic ‘Rocking’ Communication Cognitive
(mon) till (months) size hand movements trunk movements dysfunction regression
1. 35 18 + + + + +
2. 42 17 + + + + +
3. 23 7 + + - + +
4. 33 13 - + - + +
Consultant Neurologist, Department of Neurological Sciences, Christian Medical College Hospital, Vellore - 632004, Tamilnadu, India.
494 Neurology India December 2004 Vol 52 Issue 4
Kumar S, et al: Rett syndrome
activity in Cases 1 and 3 and focal epileptiform discharges in Cases abnormalities are reported in almost all cases and findings
2 and 4). CSF analysis including measles antibody titer was normal. vary with the age of the patient and the clinical stages of RS.2
Genetic analysis was not performed in our cases. EEG was abnormal in all our cases.
Rett syndrome is a genetic disorder transmitted in an X-
Discussion linked dominant fashion, 99% of the cases are sporadic, and
familial recurrence is seen in less than 1%.3 Mutations in the
Rett syndrome is characterized by profound cognitive im- MECP2 gene, located in the region Xq28, have been identi-
pairment, problems with communication, stereotypic hand fied in 70-80% of patients.12 Genetic studies are not essential
movements, and pervasive growth failure that follow a nor- for diagnosis in the majority, children with mild or atypical
mal period of development during the first six to 18 months of symptoms may require molecular genetic studies. Angelman
life.2 Diagnosis of RS is based on clinical criteria,5 as only 70- syndrome and RS may have phenotypic and EEG similari-
80% of patients with typical RS phenotype have mutations in ties. In such cases molecular genetic studies may differenti-
the RS gene. Our patients fulfilled all the essential and exclu- ate the disorders.
sion criteria. Supportive criteria noted in our patients were Treatment is symptomatic and supportive. Long-term man-
bruxism (50% of patients) and growth retardation (100% of agement involves physical and occupational therapy, speech
patients). therapy, nutritional support, seizure control and orthopedic
Clinical features of RS are classified into four stages.6 First intervention. Patients need scoliosis surveillance and surgery
stage is the stagnation period with onset between six and 18 is recommended when the curve passes 40 degrees, which is
months of age. It lasts for weeks to months and is character- associated with good outcome.13 Feeding problems may ben-
ized by developmental delay without regression. Second stage efit with changing the food texture and may require alternate
starts between one and four years of age and is characterized routes of feeding in some cases.
by regression of motor and language milestones. Stage Three In conclusion, RS is probably underdiagnosed in our coun-
or pseudostationary stage may last for several decades and is try and should be suspected in appropriate clinical situations
seen in girls with preserved ambulation. Communication may as the diagnosis can be made clinically. It should be differen-
even improve but the motor functions worsen. Stage four is tiated from cerebral palsy and autism, as the therapeutic ap-
characterized by loss of ambulation. The transition from one proach and outcomes differ.
stage to the next does not occur abruptly. All our cases were
seen in the first two stages. References
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Neuroimaging studies in RS have shown generalized cer-
ebral atrophy predominantly affecting the frontal lobes.11 EEG Accepted on 31.01.2004.
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