Early onset or syndromic epilepsy
Gene: ALPL
AD and AR hypophosphatasia (HPP). Litmanovitz et al, 2002 (11999978) lethal perinatal HPP with two missense variants. Fukazawa et al 2018 (28802630) - newborn with infantile HPP and seizures - hom for a fs variant. Belachew et al, 2013 (23479201) 2 month old boy with infantile HPP and seizures - found to be a compound het for 2 diff fs variants. Guzel Nur et al, 2016 (27086862) - infantile HPP patient who presented with pyridoxine-responsive seizures - identified a novel hom del of 2 AA. Oyachi et al, 2018 (30083035) Newborn with HPP, seizures from day 2 - treated with drugs from day 4, compound het - missense and a fs variant, parents carriers, the fs variant has been observed previously and account for 40.9% of severe alleles in the Japanese population . Whyte et al, 2019 (30979546) retrospective study of a large cohort of paediatric patients with perinatal and infantile hypophosphatasia- vit B6 depend seizures seen in 10/38 cases (26%) - no genetic analysis done on these patients as far as i can tell. 100s of mutations listed on HGMD Pro in assocation with hypophosphatasia. All of these cases with epilepsy are AR, suggests that the AR conditionas are assoc with epilepsy not AD.Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Epilepsy can be associated with hypophosphatasia; no further literature identified. From reviews below, appears to have sufficient evidence for a green gene.Created: 23 Aug 2019, 10:12 a.m. | Last Modified: 23 Aug 2019, 10:12 a.m.
Panel Version: 1.256
AR infantile hypophosphatasia and AR childhood phosphatasia assoc with epilepsy. Tenorio et al, 2017 - over 300 diff mutations in ALPL reported, disease severity variable and common clinical features are defects in bone and tooth mineralisation along with the biochemical hallmark of decreased serum alkaline phosphatase activity - no mention of seizures in any of the patient phenotypic information in this paper.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hypophosphatasia, adult 146300; Hypophosphatasia, childhood 241510; Hypophosphatasia, infantile 241500; Odontohypophosphatasia, 146300;
Publications
Kept rating as Green based on post-Webex reviews from Helen Lord and Alison Callaway.Created: 7 Sep 2019, 9:55 a.m. | Last Modified: 7 Sep 2019, 9:55 a.m.
Panel Version: 1.264
Comment on mode of inheritance: Updated Mode of Inheritance from 'BOTH monoallelic and biallelic' to 'BIALLELIC' based on Post-Webex review by Helen Lord: AR but not AD Hypophosphatasia is associated with seizures.Created: 7 Sep 2019, 9:52 a.m. | Last Modified: 7 Sep 2019, 9:52 a.m.
Panel Version: 1.264
Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset that were re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
PMID:30979546: Whyte et al., 2019 report Vitamin B6-dependent seizures in 10/38 (26%) of patients: 7 patients had documented seizures and 3 patients had a family history of seizures based upon medical records.Created: 22 Jul 2019, 11:16 a.m. | Last Modified: 27 Aug 2019, 10:18 a.m.
Panel Version: 1.258
PMID:30083035: Oyachi et al., 2018 report a newborn girl with compound het variants in ALPL (c.1559delT/p.Ser188Pro). The patient had seizures on days 2-4, treated with pyridoxine.Created: 22 Jul 2019, 11:11 a.m. | Last Modified: 22 Jul 2019, 11:11 a.m.
Panel Version: 1.172
PMID:27086862 (2018) report a female infantile hypophosphatasia patient who presented with pyridoxine-responsive myoclonic seizures and a novel homozygous mutation in the ALPL gene(c.799_804delCACTTC). Parents were heterozygous for the variant.Created: 22 Jul 2019, 11:11 a.m. | Last Modified: 22 Jul 2019, 11:11 a.m.
Panel Version: 1.172
Comment on publications: ALPL is called by its alias TNSALP in many publications.Created: 9 Jul 2019, 8:06 p.m. | Last Modified: 9 Jul 2019, 8:06 p.m.
Panel Version: 1.147
Comment on phenotypes: Hypophosphatasia, adult 146300 AD, AR;Hypophosphatasia, childhood 241510 AR;Hypophosphatasia, infantile 241500 AR;Odontohypophosphatasia 146300 AD, ARCreated: 17 Jul 2018, 9:37 a.m.
Comment on list classification: Based on review by Dr Arianna Tucci (Genomics England Clinical Fellow and Curator)Created: 17 Jul 2018, 9:34 a.m.
Associated with the phenotype in OMIM. seizures can be part of the phenotype. Note that seizures in are refractory to conventional antiepileptic drugs, but are responsive to pyridoxine.Created: 5 Jul 2018, 1 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hypophosphatasia
Tag drug-indication was removed from gene: ALPL.
Mode of inheritance for gene: ALPL was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Source Wessex and West Midlands GLH was added to ALPL.
Source NHS GMS was added to ALPL.
Publications for gene: ALPL were set to 11999978; 28802630; 23479201; 27086862; 30655187; 30083035
Publications for gene: ALPL were set to 11999978; 28802630; 23479201
Publications for gene: ALPL were set to
Arianna Tucci: Associated with the phenotype
Gene: alpl has been classified as Green List (High Evidence).
Phenotypes for gene: ALPL were set to Hypophosphatasia, adult 146300 AD, AR; Hypophosphatasia, childhood 241510 AR; Hypophosphatasia, infantile 241500 AR; Odontohypophosphatasia 146300 AD, AR
Mode of inheritance for gene: ALPL was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: alpl has been classified as Green List (High Evidence).
Expert Review Amber was added to ALPL. Panel: Genetic Epilepsy Syndromes
ALPL was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
ALPL was created by Sarah Leigh