Two non-familial cases of Galloway-Mowat syndrome carrying the homozygous mutations of WDR73 and TP53RK / Dois casos não familiares de síndrome de Galloway-Mowat portadores das mutações homozigóticas de WDR73 e TP53RK

Galloway­Mowat syndrome (GAMOS) is a rare hereditary disease manifested as a combination of nephrotic syndrome and central nervous system impairment. To date, many GAMOS cases attributed to various gene mutations have been reported such as WHAMM, NUP107, WDR73, OSGEP, and TP53RK. We detected two novel homozygous mutations of WDR73 ''NM_032856:c.G287A:p.R96K'' and TP53RK ''NM_033550:c.A193O:p.K65Q'' in two female kids of the consanguineous parents from different families using whole exome sequencing. Both patients almost manifested similar neurodegenerative phenotypes, including developmental delay, microcephaly, hypotonia, and brain atrophy on magnetic resonance imaging during infancy. WDR73-positive GAMOS case manifested a lateonset minimal nephrotic syndrome at the age 4 years while TP53RK-positive case presented nephrotic syndrome at the age 1 which progressed to steroid-resistant nephrotic syndrome due to lack of remission after 4-6 weeks of initial treatment with prednisone. Despite the brain abnormalities and the onset time difference of renal abnormalities, both patients are still alive. Given the heterogeneity of the renal phenotype among GAMOS types, accurate recognition of expanding spectrum of phenotype findings and regular renal function screening are necessary for an early diagnosis and timely treatment

A síndrome de Galloway-Mowat (GAMOS) é uma doença hereditária rara que se manifesta como uma combinação de síndrome nefrótica e comprometimento do sistema nervoso central. Até o momento, foram relatados muitos casos de GAMOS atribuídos a várias mutações genéticas, como WHAMM, NUP107, WDR73, OSGEP e TP53RK. Detectamos duas novas mutações homozigóticas de WDR73 ''NM_032856:c.G287A:p.R96K'' e TP53RK ''NM_033550:c.A193O:p.K65Q'' em duas crianças do sexo feminino, de pais consanguíneos de diferentes famílias usando o exoma completo de sequenciamento. Ambos os pacientes manifestaram fenótipos neurodegenerativos semelhantes, incluindo atraso no desenvolvimento, microcefalia, hipotonia e atrofia cerebral por ressonância magnética durante a infância. O caso GAMOS positivo para WDR73 manifestou síndrome nefrótica mínima de início tardio aos quatro anos de idade, enquanto o caso positivo para TP53RK apresentou síndrome nefrótica com um ano de idade, que progrediu para síndrome nefrótica resistente a esteroides devido à falta de remissão após quatro a seis semanas de tratamento inicial com prednisona. Apesar das anormalidades cerebrais e da diferença de tempo de início das anormalidades renais, ambos os pacientes ainda estão vivos. Dada a heterogeneidade do fenótipo renal entre os tipos de GAMOS, o reconhecimento preciso do espectro em expansão dos achados fenótipos e a triagem regular da função renal são necessários para um diagnóstico precoce e tratamento oportuno

Galloway-Mowat Syndrome in an infant caused by OSGEP gene mutation: a case report and literature review / 中国新生儿科杂志

Objective:To summarize the clinical features and pathogenic gene mutation of Galloway-Mowat syndrome (GAMOS).Methods:We retrospectively collected the medical history, physical signs, laboratory findings, imaging, and molecular data of GAMOS in an infant diagnosed at the department of Pediatrics of Women and Children's Hospital, School of Medicine, Xiamen university. Relevant literature up to December 2021, retrieved from PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang and the Chinese Medical Journal Full Text database with the terms of "Galloway-Mowat syndrome", "infant", "WDR73", "LAGE3", "OSGEP", "TP53RK" and "TPRKB".Results:The male infant with dysmorphic facial features and microcephaly at birth gradually displayed growth restriction and developmental delay. He was admitted to hospital at 3 months and 1 day due to "tachypnea for a half day", and suffered from severe pneumonia, urinary tract infection, nephrotic syndrome, repetitive convulsion, septic shock, disseminated intravascular coagulation, acute renal damage and multiple organ failure during hospitalization. He died when his family had given up treatment. Whole exome sequencing revealed a homozygous mutation c.740G>A (p.Arg247Gln) in the OSGEP gene and both of his parents were heterozygous variation carriers. In the total 14 publications (13 were in English and only 1 in Chinese) that were retrieved, with 78 patients from 58 pedigrees. Together with the index case, there were 79 patients in total. The main clinical manifestations were craniofacial and skeletal dysmorphism, as well as nervous system, renal and eye impairment. Obstetric problems were detected in 15 cases (19.0%), including intrauterine growth restriction, microcephaly, oligohydramnios and fetal distress in utero. 49 cases (62.0%) died when reported. The genetic cause of GAMOS had been reported in 79 patients: OSGEP in 36 (45.6%), WDR73 in 29 (36.7%), TP53RK in 7(8.9%), LAGE3 in 5 (6.3%), and TPRKB in 2(2.5%).Conclusions:The main clinical manifestations of GAMOS were craniofacial and skeletal dysmorphism, development delay, leukoencephalopathy, myelination defect, proteinuria and nephrotic syndrome, and associated with poor prognosis. Prenatal findings may be useful for an early diagnosis.

A Case of Galloway-Mowat Syndrome with Classic Clinical Triad in the Neonatal Period / 대한주산의학회잡지

Galloway-Mowat syndrome (GMS) is a rare autosomal recessive disorder comprising of early-onset nephrotic syndrome and central nervous system involvement including microcephaly, seizure and developmental delay. Although hiatal hernia is no longer considered essential findings for diagnosis, clinical triad of GMS included nephrotic syndrome, neurological manifestations, and hiatal hernia in the original description. We experienced a case of newborn with GMS presenting these clinical triad in neonatal period. A male infant weighing 2,250 g was born at gestational week 39+3 by cesarean section. The patient revealed mild dysmorphic facial features and microcephaly. On day 7, Nissen fundoplication was done because of hiatal hernia with gastric volvulus. At the age of 2 weeks he developed nephrotic syndrome with proteinuria and hypoalubuminemia. This is the first case of GMS that three classic findings were present in neonatal period in Korea.

A Case of Microcephaly and Early-onset Nephrotic Syndrome: Galloway-Mowat Syndrome

The Galloway-Mowat syndrome, a rare inherited disorder, is characterized by congenital microcephaly with various neurological abnormalities and early onset of nephrotic syndrome with unresponsiveness to treatment, progressive deterioration in renal function and death in early lifetime. In this report, we describe a girl with microcephaly, seizures. and psychomotor retardation who developed nephrotic syndrome at 17 months of age.

A Case of Microcephaly and Early-onset Nephrotic Syndrome: Galloway-Mowat Syndrome

The Galloway-Mowat syndrome, a rare inherited disorder, is characterized by congenital microcephaly with various neurological abnormalities and early onset of nephrotic syndrome with unresponsiveness to treatment, progressive deterioration in renal function and death in early lifetime. In this report, we describe a girl with microcephaly, seizures. and psychomotor retardation who developed nephrotic syndrome at 17 months of age.

Galloway-Mowat Syndrome in Two Siblings

We report on two Korean siblings with multiple congenital anomalies : microcephaly, gyral abnormality, minor facial anomalies, and congenital nephrotic syndrome. The first infant developed proteinuria at age 3 days. This condition appeared similar to that described by Galloway and Mowat and reviewed by Cooperstone, et al, especially the presence of abnormal gyral patterns. She died at 19 months. The second infant; the brother of the first baby had a very similar condition. These two cases may represent the first cases of Galloway-Mowat syndrome in the Korean population.