Abstract 2003

Rett Syndrome (RS) is a neurodevelopmental disorder that affects mainly, if not exclusively, girls. A necessary diagnostic criteria is deceleration of head growth during early childhood. Objective: To describe RS patients with classic clinical manifestations but without deceleration of head circumference. Method: Review of head circumference (HC) in 450 cases of RS evaluated in our institution. Ninety-eight percent have deceleration of head growth with resultant microcephaly. Twelve patients, aged 2 to 31 y/o, without evidence of deceleration of HC were identified. We documented their clinical features, EEG and MRI findings and compared them to the classic RS cases with deceleration of head growth. Results: The 12 patients identified without deceleration of head growth had classic RS features. None had ocular abnormalities, visceromegaly or neurocutaneous stigmata. They were further divided into two groups. Group1 (N=9), representing 2% of the total cases, have normal head size with no deceleration noted. Of these, 2(22%) were above the 50th percentile, 3(33%) at the 50th percentile, another 3(33%) just below the 50th percentile and 1(11%) tracking the 25th percentile for age. All of these patients have normal perinatal history, loss of purposeful hand use, stereotypic hand movement, psychomotor retardation and normal MRI. Seven out of 9 have loss of expressive language. While two, despite language delay, still have some expressive language. Six out of 9 have overt seizure disorder with typical EEG findings and 3 out of 9 have no clinical seizures. Group 2(N=3) representing 0.6% of the total cases have HC falling within -2SD from the mean since birth without subsequent deceleration noted. One patient had familial microcephaly. Two (Pts.#10 and 12) out of the three were born prematurely requiring NG feeding and phototherapy. One patient (Pt. #12) also had lipoma of the corpus callosum with rostral agenesis. Conclusion: In the absence of a biological marker, the diagnosis of RS is made on a set of established clinical criteria. Despite the absence of decelerating head growth, 12 patients in our series demonstrated classic RS features. There were no differences in perinatal history, EEG or MRI abnormalities from cases of classic RS with decelerating head growth. A subset of patients with typical clinical phenotype do not appear to have a cardinal feature of this disorder that has been a necessary criteria for its diagnosis. Whether these patients are phenocopies of RS and result from other etiologies remains to be defined when a biological marker becomes available for this disease.