|Year : 2017 | Volume
| Issue : 2 | Page : 124-127
Lissencephaly and nephrotic syndrome: Galloway-Mowat syndrome
Zahid Anwar1, Jamal Yaqoob2, Salah El-Morshedy1, Muslim Muhammad Al-Saadi1
1 Department of Paediatrics, Dallah Hospital, Riyadh, Kingdom of Saudi Arabia
2 Department of Radiology, Dallah Hospital, Riyadh, Kingdom of Saudi Arabia
|Date of Web Publication||13-Apr-2017|
Department of Paediatrics, Dallah Hospital, P. O. Box: 87833, Riyadh 11652
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
The Galloway-Mowat syndrome (GMS) is a rare autosomal recessive disorder which is characterized by the presence of renal and brain abnormalities. Hiatal hernia, initially thought to be a part, is longer a consistent feature of syndrome. The neurological features include microcephaly, developmental delay, seizures, hypotonia, abnormal sulci and gyri, and abnormal cerebellum. The renal finding is that of nephrotic syndrome, but histopathologically may vary to focal segmental sclerosis or mesangial sclerosis. Nephrotic syndrome is usually diagnosed before the age of 2 years and may lead to renal failure. We describe a 29-week preterm baby of unrelated parents with intrauterine growth retardation, dysmorphic features, lissencephaly, and nephrotic syndrome. Nephrotic syndrome was diagnosed at the age of 2 months. The baby had progressive neurological deterioration and died at the age of 14 weeks.
Keywords: Galloway-Mowat Syndrome, lissencephaly, nephrotic syndrome, neonate
|How to cite this article:|
Anwar Z, Yaqoob J, El-Morshedy S, Al-Saadi MM. Lissencephaly and nephrotic syndrome: Galloway-Mowat syndrome. J Clin Neonatol 2017;6:124-7
|How to cite this URL:|
Anwar Z, Yaqoob J, El-Morshedy S, Al-Saadi MM. Lissencephaly and nephrotic syndrome: Galloway-Mowat syndrome. J Clin Neonatol [serial online] 2017 [cited 2020 Sep 30];6:124-7. Available from: http://www.jcnonweb.com/text.asp?2017/6/2/124/204508
| Introduction|| |
Galloway-Mowat Syndrome (GMS; OMIM 251300) is a rare genetic disorder characterized by early onset nephrotic syndrome and neurological structural and developmental abnormalities. It was first described in 1968 and was also known as Microcephaly-Hiatal hernia syndrome  though in later case reports, hiatal hernia has not been a consistent finding. Over the years, described in around 60 cases, its spectrum has expanded to include dysmorphic features, growth retardation, and variety of neuropathological findings as well as heterogeneous renal histopathology.
It is known to be autosomal recessive with some recent studies pointing to WDR73 gene mutations which is expressed in kidneys and brain.
We describe a case from our neonatal intensive care unit (NICU) which was initially diagnosed as lissencephaly but later on developed nephrotic range proteinuria and diagnosis was revised as Galloway-Mowat Syndrome.
| Case Report|| |
A 29 + 5-week preterm, weighing 750 g was delivered to primigravida mother. The parents were Yemini in origin and were not related. The mother was 31-year-old with primary infertility for 15 years and conceived this time by in vitro fertilization. Mother had gestational diabetes controlled with diet and asthma treated with ventolin inhaler use during pregnancy. She was not immune to rubella on antenatal testing. At 29-week gestation, fetus was noted to have intrauterine growth retardation with oligohydramnios. Only one dose of dexamethasone could be given antenatally and baby was delivered by emergency Caesarean section because of fetal distress.
The baby was resuscitated, intubated, and given surfactant in the operating room. In NICU, baby was started on mechanical ventilation. On examination, baby was found to be dysmorphic with low set bat-shaped ears [Figure 1], absent red reflex, short neck, clinodactyly with clenched hands [Figure 2], single crease, poor spontaneous movements, undescended testes, arthrogryposis (limited abduction at hip, limited extension of fingers), and suspected rocker bottom feet. Based on the findings, Edward syndrome was suspected. The ophthalmological consultation revealed bilateral cataracts. Echocardiography showed only a small patent ductus arteriosus.
The further investigations over ensuing period showed suspected lissencephaly on brain ultrasounds, which was confirmed on brain magnetic resonance imaging as lissencephaly type 1. Radiological findings in detail showed lissencephaly (type-1 variety) with abnormal four-layered thick cortex at the level of cavum septi pellucidi, near complete agyria, hypoplastic sulci, and hypoplastic cerebellum and vermis [Figure 3] and [Figure 4]. Mild ventriculomegaly with cavum septi pellucidi was also noted.
|Figure 3: Axial fluid-attenuated inversion recover image of type-1 lissencephaly. Thick four-layered abnormal cortex (black arrow) at the level of cavum septi pellucidi (white arrow). Total cortical mantle thickness was 14.2 mm in the frontal region (which comprises of cortical zone of 1.6 mm, Sub-plate zone of 4.2 mm, Intermediate zone of 3.6 mm, and periventricular zone of 4.8 mm)|
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|Figure 4: Magnetic resonance imaging brain Sagittal T2-weighted image showing hypoplastic cerebellum (black arrow)|
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The chromosomal analysis was 46XY and baby had undescended testes in inguinal canal. Metabolic screen was negative for any metabolic derangement.
Consultant neonatologist after discussion with consultant radiologists and pediatric neurologist and literature review counseled the parents about severe morbidity and likely mortality. The parents, however, decided to continue with the routine care of the baby.
During stay in the NICU, multiple attempts to extubate the baby to nasal continuous positive airway pressure failed as baby became increasingly more bradypniec. Overall activity and movements of the limbs declined with time as well.
At around 60 days of life, baby started having edema. Investigations revealed heavy proteinuria (4+) and very high urinary albumin to creatinine ratio (up to 6276 mg/g craet.), which remained high till the time of death of baby. Multiple albumin transfusions were needed to be given to the baby for falling serum albumin levels (mostly around 28 g/L) and edema. The renal function tests (blood urea nitrogen of 1.6 mmol/L and serum creatinine of 27 umol/L) as well as urinary culture results were normal. Diagnosis was revised to Galloway-Mowat Syndrome due to the presence of nephrosis along with brain abnormalities. Trial of steroids for nephrosis was not successful. The genetic studies could not be done because of financial constraints.
The baby expired on 98th day of life for central hypoventilation and suspected sepsis.
| Discussion|| |
GAM, first reported in 1968, has been described in around 60 patients having combination of early nephrotic syndrome along with brain anomalies.
Prenatal ultrasound findings described in literature are intrauterine growth retardation, microcephaly, and oligohydramnios usually late in gestation.
The nephrotic syndrome is usually diagnosed before 2 years of life but has been reported later in few reports. The renal histology has variable findings such as minimal change disease, focal segmental glomerulosclerosis, and diffuse mesangial sclerosis. The nephrotic syndrome is typically steroid resistant., The onset of nephrotic syndrome in our baby has been at 2 months of age which is a classical finding.
The reported brain anomalies include microcephaly, convulsions, hypotonia, and hydrocephalus. The patient may develop global developmental delay and spastic quadriplegia with limited joint mobility later in the life. Brain imaging findings include abnormal cerebral sulci and gyri, ventricular dilatation, small brainstem, thin corpus callosum, delayed myelination, and cerebellar hypoplasia., Our patient had lissencephaly which is the severest form of the gyral abnormalities usually reported in the GMS.
In addition, facial dysmorphism, large ears, hypertelorism, epicanthal folds, large nose with prominent nasal bridge and tip, wide mouth, and strabismus have also been mentioned.
The congenital nephrotic syndrome can be classified as primary or secondary. It occurs secondary to congenital syphilis (typically) but can be found also in other congenital infections (toxoplasmosis, rubella, cytomegalovirus, HIV, hepatitis B) and infantile systemic lupus erythematosus. Genetic disturbances affecting the glomerular diaphragmatic membrane, mostly autosomal recessive, constitute primary congenital nephrotic syndrome. The prototype of these genetic disturbances is Finnish type congenital nephrosis which presents usually around 2 months of age and affects only kidneys in most of the cases. Other syndromes include Denys-Drash syndrome (nephrosis with rapid progression to end-stage renal disease, male pseudohermaphroditism, and Wilms' tumor), Frasier syndrome (gonadal dysgenesis with nephrosis occurring late in childhood), Nail-patella syndrome (congenital nephrotic syndrome associated with elbow and knee abnormalities) and Pierson syndrome. Pierson syndrome is characterized by congenital nephrotic syndrome starting in first 2 months of life, eye abnormalities typically microcoria (but cataracts, glaucoma, retinal detachments, and blindness may occur), and neurological disabilities and developmental delays in infancy.
Galloway-Mowat syndrome has autosomal recessive inheritance. Recently, homozygous protein truncating mutations in WDR73 were identified in some of the families. This gene maps to chromosome 15q25.2 which encodes a 378 amino acid protein., WDR73 is expressed in brain and kidneys and plays role in cell architecture and survival. Further studies are ongoing.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]