Case:Patient 2, female, 2.5 years old
DiseaseAssertion:CDKL5 Disorder
FamilyInfo:De Novo with an unremarkable family history.
ParentalGenotype:Not provided
CasePresentingHPOs:HP:0032792, HP:0007359, HP:0011154, HP:0002194, HP:0010862, HP:0000750, HP:0012434, HP:0000710, HP:0100023, HP:0000252, HP:0009062, HP:0010845, HP:0020174, HP:0010841.
CaseHPOFreeText:
Patient history
@ 2 months to 2.5 years - Patient 2 experienced tonic and focal seizures with autonomic symptoms.
@ 2 years - Patient 2 was diagnosed with CDKL5 disorder.
Patient 2 had severe delayed gross motor development, severe delayed fine motor development, severe delayed language development and delayed social development. Patient 2 had hyperoral and hand flapping stereotypies. She also had microcephaly (< 2 SD) and axial hypotonia.
Patient 2 was given a brain EEG which detected Delta slowing of the background followed by generalized attenuation during seizures and multifocal interictal
epileptiform abnormalities.
@ 2.5 years - Patient 2 experienced seizures in clusters.
Treatments
Antiepleptic treatments included:Phenobarbital, Topirimate, Clobazam, Valproate, Keppra, Vitamin B6,
Phenytoin, Lamotrigine, Nitrazepam, Oxcarbazepine,
Mirtazipine, KCI, Levetiracetam, ant ketogenic diet.
Patient 2 was also treated with Carnitine. Patient 2's seizures seem to have changed in type over time but continued.
Other testing
Tests were conducted on Patient 2 to obtain data in the following areas: NBS, lactate, lipoprotein profile, plasma and urine amino acids, urine organic acids, acylcarnitine profile, total and free serum carnitine levels, plasma ammonia, total plasma homocysteine, serum CK, liver enzymes, urine alpha-AASA, creatine, biotinidase, VLCFA, Batten disease screen, CSF analysis
(amino acids, lactate, glucose, protein, cell count,
neurotransmitters), MRI-brain with spectroscopy, and
karyotype.
CaseNotHPOs:Not provided
CaseNotHPOFreeText:Not provided
CasePreviousTesting:Patient 2 was given a gene sequence test for the genes SCNIA and MECP2. No gene mutation was found for these two genes.
PreviouslyPublished:Not previously published
GenotypingMethod:Patient 2 was given a CDKL5 gene sequence test. The test detected a mutation in the CDKL5 gene.
Gene:CDKL5
Variant:c. 2480_2486dupCAGATCT. frameshift
The authors state that CDKL5 gene sequencing detected a de novo duplication in exon 17,
c. 2480_2486dupCAGATCT, resulting in a frameshift (Boston University School of Medicine, Center for Human Genetics, Boston, MA). This is a novel change that has not been reported before in ExAC. Only pathogenic point mutations in exon 17 have previously been
reported. In a patient with a previously reported frameshift mutation in exon 18, a truncated CDKL5 transcript was detected. A truncated protein would lack the C-terminus and would not localize correctly in the cell, as demonstrated in vitro. Accordingly, any reading frame altering mutations proximal to exon 18 are null-variants. Therefore, this mutation is classified as pathogenic according to ACMG criteria.
HGVS:Not provided
ClinVarID:547188
NM_001323289.2 (CDKL5): c. 2480_2486dup (p. Gln830fs)
Allele ID: 538303
CAID:Not found
gnomAD:Not found
MultipleGeneVariants:Not provided