Original articleEpilepsy and neurological findings in 11 individuals with 1p36 deletion syndrome☆
Introduction
Mental retardation (MR) is one of the most frequent causes of serious neurological handicap that occurs in 2–3% of the human population. The underlying causes of MR are heterogeneous and may involve genetic and/or environmental factors. The causes of mental retardation are unexplained in more than half of all cases. The study of MR etiology has always been a challenge [1]. Attention has recently focused on cryptic subtelomeric chromosome rearrangements as a cause of dysmorphology and mental retardation [2], [3], [4], [5]. Technological advancement in the development of subtelomere fluorescence in situ hybridization (FISH) probes and the clinical application of detection kits for subtelomere rearrangements has enabled large-scale surveys of patients with mental retardation and/or multiple congenital anomalies. Cryptic subtelomeric rearrangements now account for 5–7.4% of moderately or severely mentally handicapped children, who had no identifiable causes [5].
Terminal deletion of 1p is recognized as a syndrome with multiple congenital anomalies and mental retardation [6], [7], [8], [9]. The syndrome is characterized by severe mental retardation, growth retardation, intractable seizures, hypotonia, precocious puberty, characteristic facial appearance, and cardiomyopathy. The prevalence of the syndrome is estimated to be one in 5000–10,000, making it the most common terminal deletion syndrome. Maternally derived de novo deletions are significantly more frequent than paternally derived deletions. The deletion size varies in each family, providing phenotypic variability as a result of haploinsufficiency of different genes. The critical region for moderate to severe mental retardation is defined distally by D1S243 and proximally by D1S468 [7]. In most cases, FISH confirmed the deletion with probes D1Z2 and p58. The subtelomere assay using the Chromophore Multiprobe-T Cytocell device (Cytocell) is also used to detect the 1p36 deletion in patients with unclassified multiple congenital anomalies/mental retardation (MCA/MR) syndromes [4]. Disadvantages of these methods for widespread screening are the cost and the fact that it is not available to all clinical settings [10].
To elucidate the clinical characteristics of the newly delineated 1p36 deletion syndrome, we studied 11 Japanese patients with the 1p36 deletion syndrome and reviewed the clinical findings. We further refined the common critical deletion interval among patients with the disorder. This information is important for health practitioners and families supporting patients with the disorder.
Section snippets
Patients and methods
Eleven Japanese patients with the 1p36 deletion syndrome were included in this study. Of the 11 patients, 9 were diagnosed clinically according to facial appearance, neurological features and characteristic physical symptoms. Diagnoses were confirmed by FISH analysis with the midisatellite probe p1-79/D1Z2 (ATCC, Rockville, MD), which maps to 1p36.3. Cases 8 and 10 were diagnosed by standard G-bands by trypsin using Giemsa (GTG) technique and high resolution banding procedures. All patients
Results
Phenotypic data based on medical records was analyzed for 11 patients (four male and seven female). The clinical details are summarized in Table 1. Severe developmental delay and feeding difficulties were common to all cases during the infantile period. Prenatal growth retardation was noted in patients with a visible deletion within 1p36.3 detected by standard GTG technique (patient 8 and 10). This observation may not be significant in the 1p36 deletion syndrome as prenatal growth retardation
Discussion
The 11 patients described in this study all have severe mental retardation and similar facial features, but other congenital anomalies are variable. Two patients had a deletion within 1p36 that was detected by standard GTG technique. The other 9 patients had submicroscopic deletions confirmed using FISH using the D1Z2 probe.
The mutations in all patients were sporadic, and the possibility of cryptic translocation was not evaluated. Growth parameters were prenatally retarded in patients with
Acknowledgements
The Kawano Masanori Memorial Foundation for Promotion of Pediatrics supported this study. The authors are grateful to Dr Yoshikatsu Eto (Jikei University) for his valuable comments. The authors also wish to thank the patients and their families for contribution to this study.
References (16)
- et al.
Subtle chromosomal rearrangements in children with unexplained mental retardation
Lancet
(1999) - et al.
Chromosome 1p36 deletions: the clinical phenotype and molecular characterization of a common newly delineated syndrome
Am J Hum Genet
(1997) - et al.
Physical map of 1p36, placement of breakpoints in monosomy 1p36, and clinical characterization of the syndrome
Am J Hum Genet
(2003) - et al.
Diagnostic evaluation of developmental delay/mental retardation: an overview
Am J Med Genet
(2003) - et al.
The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation
Nat Genet
(1995) - et al.
Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis
J Med Genet
(2000) - et al.
Study of 250 children with idiopathic mental retardation reveals nine cryptic and diverse subtelomeric chromosome anomalies
Am J Med Genet
(2002) - et al.
Molecular refinement of the 1p36 deletion syndrome reveals size diversity and a preponderance of maternally derived deletions
Hum Mol Genet
(1999)
Cited by (38)
Electroclinical features of epilepsy associated with 1p36 deletion syndrome: A review
2018, Epilepsy ResearchMicroarray analysis of 50 patients reveals the critical chromosomal regions responsible for 1p36 deletion syndrome-related complications
2015, Brain and DevelopmentCitation Excerpt :Patients with this syndrome exhibit common clinical features, including intellectual disability (ID) and characteristic craniofacial features; such as straight eyebrows, deep-set eyes, epicanthus, and a pointed chin [6–9]. Although the levels of ID vary among patients, craniofacial features are commonly seen [10]. The patients with the 1p36 deletion syndrome also show many other complications, including hypotonia, seizures, hearing loss, structural heart defects, cardiomyopathy, ophthalmological abnormalities, and behavior abnormalities [7].
Monosomy 1p36 - A multifaceted and still enigmatic syndrome: Four clinically diverse cases with shared white matter abnormalities
2014, European Journal of Paediatric NeurologyCitation Excerpt :All aforementioned genes were observed to be deleted in our patients. The prevalence of epilepsy in 1p36 deletion syndrome has been estimated as 44–58%.5,12,14 In most patients, epilepsy starts within the first six months of life, neonatal seizures and seizure onset after ten years tend to be the exceptions.12,14
Clinical review of genetic epileptic encephalopathies
2012, European Journal of Medical GeneticsCitation Excerpt :Epilepsy is usually well controlled with conventional anticonvulsants, but there are some reports of refractory cases of infantile spasms treated with vigabatrin and/or steroids [156,157]. Some experts advocate the short term use of corticotropin [158] or steroids for effective control of infantile spasms [157]. Brain MRI findings may include cortical atrophy and thin corpus callosum.
- ☆
The Paper is based on the Lecture given at the Sixth Annual Meeting of the Infantile Seizure Society, Tokyo, March 15–16, 2003.