MMMM syndrome (macrocephaly, megalocornea, motor and mental retardation) and refractory epilepsy.

Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre RS, Brazil: MD, Child Neurologist; MD, Geneticist; Ph.D. Child Neurologist, Pediatric Neurology Residency Program Preceptor; Ph.D. Child Neurologist, Adjunct Professor of Pediatrics, Head of Pediatric Neurology Unit. The Neuhauser syndrome was first described in 1975. Three siblings in the same family and four other sporadic patients were found to have severe mental retardation, hypotonia, seizures, megalocornea (cornea diameter ≥13 mm) and hypoplasic irises, associated with minor dysmorphic findings, such as epicanthal folds, frontal bossing and depressed nasal bridge. Neuhauser suggested a possible recessive autosomal inheritance and called the condition MMR syndrome (megalocornea and mental retardation). Since then, several other cases with similar signs and symptoms were reported in the literature, although some also had different and additional clinical findings . For example, Tominaga et al. described hearing impairment; Balci et al. reported two cases of Neuhauser syndrome with hypoplasia of corpus callosum; Yarar et al. found associated Peter’s anomaly; and Margari et al. cited a transient hypothyroidism during a five year follow up of one case of Neuhauser syndrome. In 1990, Frydman et al. described two patients with the MMR syndrome who had macrocephaly, and called this variation of the Neuhauser syndrome as the MMMM (macrocephaly, megalocornea, motor and mental retardation) syndrome. In 1991, Kimura et al. described a patient with the MMR syndrome associated with hypothyroidism and myelination delay confirmed by cranial magnetic resonance studies. Other findings described in the literature are bifid uvula, diffuse cortical atrophy, micrognathia, scoliosis, short stature, microcrania, hypertelorism, and hypotonia. The heterogeneity of this syndrome led Verloes to suggest 5 subtypes: Subtype 1: a recessive form, as described by Neuhauser, with iris hypoplasia and minor anomalies; Subtype 2: a recessive form, as described by Franky-Temtay, with camptodactyly, scoliosis and growth retardation; Subtype 3: a recessive form, with normal irises, severe hypotonia, relative or absolute macrocephaly and other minor anomalies; Subtype 4: a possible Frydman type, with normal irises, macrocephaly and obesity; Subtype 5: provisionally unclassifiable cases. The objective of this study is to describe a case of Neuhauser-type dysmorphism with refractory epileptic seizures.