Lopes-Maciel-Rodan Syndrome

A number sign (#) is used with this entry because of evidence that Lopes-Maciel-Rodan syndrome (LOMARS) is caused by compound heterozygous mutation in the HTT gene (613004) on chromosome 4p16.

Clinical Features

Lopes et al. (2016) reported an 18-year-old girl with a neurodevelopmental disorder who met diagnostic criteria for Rett syndrome (RTT; 312750). She showed developmental regression around 6 months of age, and developed complex partial seizures around 8 months. Additional features included swallowing problems, dystonia, bradykinesia, and continuous manual stereotypies without chorea. She had severe intellectual disability with poor speech, bruxism, kyphosis/scoliosis, small and cold hands and feet, diminished response to pain, and respiratory, sleep, and gait dysfunction. Brain imaging showed atrophy of the striatum, particularly the caudate nuclei, as well as mild atrophy of the cortex and cerebellar vermis.

Rodan et al. (2016) reported a consanguineous family from Ecuador in which 3 sibs had a neurodevelopmental disorder characterized by severe global developmental delay since birth, central hypotonia progressing to spastic quadriparesis, intellectual disability with poor or absent speech, and feeding difficulties. More variable features included dystonia, midline stereotypies, and high myopia. One patient had seizures and 1 patient had bruxism. One of the patients died unexpectedly at age 7 years. Two of the sibs had features reminiscent of Rett syndrome.

Inheritance

The transmission pattern of LOMARS in the family reported by Rodan et al. (2016) was consistent with autosomal recessive inheritance.

Molecular Genetics

In a girl with LOMARS, Lopes et al. (2016) identified compound heterozygous missense mutations in the HTT gene (P703L, 613004.0002 and T1260M, 613004.0003). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed, but Lopes et al. (2016) noted that the HTT gene interacts with MECP2 (300005), which is mutant in Rett syndrome. Mutations in MECP2 were excluded in the patient.

In 3 sibs, born of parents of Ecuadorian descent, with LOMARS, Rodan et al. (2016) identified compound heterozygous mutations in the HTT gene (613004.0004 and 613004.0005). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variants and studies of patient cells were not performed. Mutations in MECP2 were excluded in the sibs.