Classical West “syndrome” phenotype with a subtelomeric 4p trisomy

Abstract

We report a girl with mild mental retardation with onset of infantile spasms at age of 9 months. Treatment with a short course of adrenocorticotropic hormone (ACTH) was successful. Initially, a diagnosis of idiopathic West syndrome, with good neurological outcome and disappearance of epilepsy after treatment, was made. Conventional karyotype was normal. Reinvestigations were done at age 8 years, because of a new pregnancy. Karyotyping of both parents was done because of mild dysmorphic features in the proband, and to eliminate other causes than early age epilepsy as the etiology of her mental retardation. Parental karyotypes showed a balanced paternal translocation (4p;17q) resulting in partial 4p trisomy, without significant 17q monosomy in the proband. Chromosomal abnormalities usually lead to a severe West syndrome with poor prognosis of neurological outcome (persistent severe epilepsy, mental retardation, and behavioral disturbances). The presence of an undetected cytogenetic anomaly in our proband with transient hypsarythmia is unusual and led us to propose systematic telomeric screening in apparently "idiopathic" West syndrome patients with mild mental retardation and subtle dysmorphic features.

Microduplication of 4p16.3 due to an unbalanced translocation resulting in a mild phenotype

“…The dysmorphic features include a prominent glabella, bulbous nose with a flat nasal bridge, retrognathia, abnormal ears, and rocker bottom feet [Gonzalez et al, 1977; Patel et al, 1995]. There have been several patients with trisomy 4p described in the medical literature that have documented involvement of the WHS loci, however, almost all cases have been cytogenetically detectable duplications, and, therefore, larger than the duplication present in our case [Cotter et al, 2001; Tschernigg et al, 2002; Gerard‐Blanluet et al, 2004; Takeno et al, 2004; Bartocci et al, 2008]. Our patient has none of the severe features described in these patients.…”

Recent developments in the genetics of childhood epileptic encephalopathies: impact in clinical practice

“…However, screening for potentially deleterious CDKL5 mutations in additional WS cohorts yielded negative results. Other chromosomal anomalies associated with WS include partial 4p trisomy 32 , balanced translocations t(X;18)(p22;p11.2) 33 and t(2;6)(p15;p22.3)…”

CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental retardation in female patients

“…3 They have also been reported in association with several different chromosomal anomalies including 15q duplication 4 and subtelomeric rearrangements. 5 Mutations in three genes have been associated with X linked infantile spasms (ISSX, OMIM 308350): Aristaless related gene (ARX, OMIM 300382), 6 cyclin dependent kinase like 5 (CDKL5, OMIM 300203), 7 and the sodium channel neuronal type 1 a subunit (SCN1A, OMIM 182389). 8 Pathogenic ARX mutations have so far only been reported in males, some of whom have infantile spasms.…”