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| Fetal anomalies v1.70 | ATP7A |
Zornitza Stark changed review comment from: Well established gene-disease association, IUGR is a feature.; to: Well established gene-disease association, IUGR is a feature. Treatment: subcutaneous injections of copper histidine or copper chloride ClinGen has assessed as moderate evidence for actionability. Neonatal treatment with subcutaneous copper-histidine (initiated before 30 days of life) is recommended for asymptomatic males with a diagnosis of MD, but is not recommended for symptomatic boys or after 30 days of life. Treatment should be continued indefinitely. In an open-label clinical trial, 12 patients with MD treated with copper-histidine within 22 days of life had 92% survival after a mean follow-up of 4.6 years compared to 13% in a historical control group of 15 patients treated after a late diagnosis (mean age at diagnosis: 163 ± 113 days, range: 42 to 390). Two of the 12 patients with earlier treatment had normal neurological development. A second open-label trial of 35 presymptomatic patients receiving copper-histidine at less than a month of age reported significant improvement of four major neurodevelopmental (gross motor, fine motor/adaptive, personal/social, and language) domains and a non-significant lower mortality (28.5% vs 50%) at age of 3 years (or age of death) compared to 22 patients treated later and after onset of symptoms. |
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| Fetal anomalies v0.4253 | SYT2 |
Belinda Chong gene: SYT2 was added gene: SYT2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SYT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SYT2 were set to 25192047; 32776697; 32250532; 30533528 Phenotypes for gene: SYT2 were set to Myasthenic syndrome, congenital, 7, presynaptic, MIM# 616040; Myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive MIM#619461 Review for gene: SYT2 was set to GREEN gene: SYT2 was marked as current diagnostic Added comment: Myasthenic syndrome bi-allelic #619461- Decreased fetal movements Mono-allelic disease, PMID 25192047 and 30533528: dominant missense variants in SYT2 reported as a rare cause of distal motor neuropathy and myasthenic syndrome, manifesting with stable or slowly progressive distal weakness of variable severity along with presynaptic NMJ impairment in three families. These variants are thought to have a dominant-negative effect on synaptic vesicle exocytosis, although the precise pathomechanism remains to be elucidated. Bi-allelic disease: 32250532 and 32776697, 8 individuals from 6 families, with biallelic loss of function variants in SYT2, clinically manifesting with severe congenital onset hypotonia and weakness, with variable degrees of respiratory involvement. Electrodiagnostic findings consistent with a presynaptic congenital myasthenic syndrome (CMS) in some. Treatment with an acetylcholinesterase inhibitor pursued in 4 indviduals showed clinical improvement with increased strength and function. Sources: Literature |
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| Fetal anomalies v0.3915 | ALB |
Krithika Murali gene: ALB was added gene: ALB was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ALB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALB were set to 23730173; 15300429; 31057599 Phenotypes for gene: ALB were set to Analbuminemia- MIM#616000 Review for gene: ALB was set to GREEN Added comment: Biallelic variants associated with congenital analbuminaemia. Prenatal features include IUGR and oligohydramnios. Allelic condition OMIM# 615999 Mono-allelic disease and dysalbuminemic hyperthyroxinemia: gain-of-function mechanism, missense variants of ALB with increased affinity for thyroid hormones. Immunoassay methods may show variably elevated free thyroid hormone levels. Individuals are euthyroid and identification is important to avoid unnecessary medical or surgical treatment. Sources: Literature |
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| Fetal anomalies v0.3718 | KMT2E |
Zornitza Stark changed review comment from: 38 individuals from 36 families reported. Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. Additional common features include autism, macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. The four individuals with missense variants presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E postulated to explain this divergence in phenotype.; to: Micro/macrocephaly reported, see below, age of onset uncertain. Non-specific brain abnormalities also. 38 individuals from 36 families reported. Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. Additional common features include autism, macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. The four individuals with missense variants presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E postulated to explain this divergence in phenotype. |
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| Fetal anomalies v0.3662 | GATM | Zornitza Stark Marked gene: GATM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3662 | GATM | Zornitza Stark Gene: gatm has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3662 | GATM | Zornitza Stark Phenotypes for gene: GATM were changed from ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY to Cerebral creatine deficiency syndrome 3, MIM# 612718 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3661 | GATM | Zornitza Stark Publications for gene: GATM were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.3660 | GATM | Zornitza Stark edited their review of gene: GATM: Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1634 | ATM | Zornitza Stark Marked gene: ATM as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1634 | ATM | Zornitza Stark Gene: atm has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1634 | ATM | Zornitza Stark Phenotypes for gene: ATM were changed from ATAXIA-TELANGIECTASIA to Ataxia-telangiectasia, MIM# 208900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1633 | ATM | Zornitza Stark reviewed gene: ATM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Ataxia-telangiectasia, MIM# 208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1220 | CHRNA3 |
Zornitza Stark changed review comment from: Five individuals from three unrelated families.; to: Five individuals from three unrelated families. Onset is in utero or early childhood. Affected individuals have impaired neuronal bladder and ureteral innervation causing coordination defects that result in secondary structural defects of the renal system, including hydronephrosis, vesicoureteral reflux (VUR), and small kidneys, that may result in chronic kidney disease as well as recurrent urinary tract infections (UTIs). Surgical treatment of VUR is not effective. Most individuals also have additional autonomic features, most commonly impaired pupillary reflex and sometimes orthostatic hypotension. |
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| Fetal anomalies v0.1136 | CA5A | Zornitza Stark changed review comment from: Episodic metabolic decompensation rather than true ID, majority have had normal neurological outcome with appropriate treatment of acute crises.; to: Episodic metabolic decompensation, majority have had normal neurological outcome with appropriate treatment of acute crises. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.825 | MAPKAPK5 |
Zornitza Stark gene: MAPKAPK5 was added gene: MAPKAPK5 was added to Fetal anomalies. Sources: Expert Review Mode of inheritance for gene: MAPKAPK5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAPKAPK5 were set to 33442026 Phenotypes for gene: MAPKAPK5 were set to Developmental delay, variable brain anomalies, congenital heart defects, dysmorphic Review for gene: MAPKAPK5 was set to GREEN Added comment: 3 individuals from 2 families with severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet. Exome sequencing identified different homozygous truncating variants in MAPKAPK5 in both families, segregating with disease and unaffected parents as carriers. Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization. Sources: Expert Review |
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| Fetal anomalies v0.764 | ABCD4 |
Zornitza Stark changed review comment from: Described clinical features include feeding difficulties, failure to thrive, hypotonia, seizures, developmental delay, and hematological abnormalities. Normal neurodevelopmental outcomes with treatment reported. At least 6 affected individuals reported.; to: Described clinical features include feeding difficulties, failure to thrive, hypotonia, seizures, developmental delay, and haematological abnormalities. Normal neurodevelopmental outcomes with treatment reported. At least 6 affected individuals reported. Congenital anomalies are very rarely reported, uncertain if they are part of the phenotype. |
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| Fetal anomalies v0.0 | GATM |
Zornitza Stark gene: GATM was added gene: GATM was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: GATM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GATM were set to ARGININE:GLYCINE AMIDINOTRANSFERASE DEFICIENCY |
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| Fetal anomalies v0.0 | ATM |
Zornitza Stark gene: ATM was added gene: ATM was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ATM were set to ATAXIA-TELANGIECTASIA |
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