Exclusion of the dymeclin and PAPSS2 genes in a novel form of spondyloepimetaphyseal dysplasia and mental retardation.

Spondyloepimetaphyseal dysplasias (SEMD) represent a heterogeneous group of conditions composed of at least 15 well-defined entities. The classification is based on clinical, radiological and molecular findings. Among them, several conditions also include a mental retardation (MR) syndrome, namely Wolcott-Rallison syndrome, Dyggve-Melchior-Clausen syndrome (DMC) and lysosomal storage disorders. Here, we report on a novel form of SEMD with MR in two Pakistani sisters born to first-cousin parents. SEMD, MR, microcephaly, ataxia, facial dysmorphism and hirsutism of back and legs were noted in the two children. Skeletal findings included flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, small carpal bones and narrow iliac wings without lacy pelvis iliac crest. Similarities with DMC prompted us to test and eventually exclude the DMC gene, dymeclin, by direct sequencing. Similarly, we excluded the PAPSS2 gene (3'-alpha phosphoadenosine 5'-phosphosulphate synthase 2) responsible for SEMD Pakistani type. The combination of features observed in the two sisters does not fit with any previously reported SEMD and represents therefore a novel form of autosomal recessive SEMD with MR.

The nonmalformed hemisphere is secondarily impaired in young children with hemimegalencephaly: a pre- and postsurgery study with SPECT and EEG.

PURPOSE: To study separately the functional value of each cerebral hemisphere in hemimegalencephaly (HME). HME is a unique model of unilateral hemispheric lesion, but one suspects that the non-HME hemisphere also could be functionally impaired because the postsurgery outcome is less favorable than expected. METHODS: We performed simultaneous prolonged EEG and 133-xenon SPECT (single-photon emission computed tomography); we measured the absolute values of cerebral blood flow (CBF) in both hemispheres and compared them with the normal values previously acquired. Thirteen patients (aged 5-38 months) underwent 31 examinations, 20 before surgery (hemispherotomy) and 11 after. RESULTS: In the HME hemisphere, we confirmed the presurgical mixture of increased and decreased CBF due to intermittent ictal discharges. After surgery, CBF was decreased in most cases. In the non-HME hemisphere, presurgery CBF was abnormal in 60% of the patients, increased and related mostly to diffuse interictal spikes on the same side, whereas normal CBF cases had focal spikes. After surgery, CBF was normal in 82% of cases, corresponding to an EEG without diffuse spikes. In the six patients longitudinally studied, CBF dramatically decreased after surgery in the HME hemisphere, whereas in the non-HME hemisphere, CBF was mostly normal very early (three fourths before 2 months), increased as soon as 3 months, and normalized only after hemispherotomy, the more rapidly the child was operated on, the earlier it was. CONCLUSIONS: This study shows that the function of the nonmalformed hemisphere is impaired as soon as the first months of the course of HME but can be restored after surgery. Our data support the recommendations to operate on the children as early as possible.