Brief clinical report and review: The Marden-Walker syndrome

We have studied a sibship with one confirmed and three probable cases of the Marden-Walker syndrome (MWS). Our patient had the major manifestations of blepharophimosis and squint; narrowly arched palate with micrognathia; small mouth and mouth-breathing; facial deformities and distortions; congenital muscle weakness with resulting scoliosis; mild pectus excavatum; camptodactylies and hip and finger joints subluxation. In addition, he had small, apparently low-set and slightly malformed auricles with a unilateral preauricular tag. However, he had no apparent renal or cardiovascular involvement. Results of CPK, EMG, and of histochemical, light microscopic, and ultrastructural studies of muscle biopsy do not suggest a primary myopathy but rather CNS related weakness/hypotonia with small muscle mass and hypoactive DTRs. This pathogenetic hypothesis is confirmed by the presence of severe mental retardation and minor brain changes suggesting cortical atrophy. In five previously reported cases there has been microcephaly. Phenotype analysis does not convince that the MWS is a true malformation syndrome, but rather hints at the possibility of a congenital metabolic dysplasia. Genetic analysis demonstrates autosomal-recessive inheitance in this and two other instances; primarily sporadic occurrence leaves open the possibility of genetic heterogeneity.     

Early neurological manifestations and brain anomalies in Marden-Walker syndrome.

We report on an infant with the Marden-Walker syndrome. In addition to the consistent neurological abnormalities described previously in this syndrome, the infant had a striking neurological constellation, absence of primitive reflexes, jerky eye movements, failure to habituate to repeated stimuli, inadequate behavior development, and absence of orientation responses to visual or auditory stimuli. Muscle biopsy showed a similar pattern to the congenital fiber-type disproportion. Ultrasonograms and magnetic resonance imaging of his brain demonstrated absence of corpus callosum, colpocephaly, hypoplastic brainstem, hypoplasia of the inferior vermis and of the cerebellar hemispheres. These findings further delineate this syndrome and suggest that prenatal central nervous system (CNS) dysfunction, mainly of the cerebellum and brainstem, may play a significant role in the pathogenesis of the Marden-Walker syndrome.     

Expanded spectrum of findings in Marden-Walker syndrome

Recently, we examined a small-for-gestational age infant with blepharophimosis, congenital contractures of elbows, hips, and knees, fixed facial expression, and hypotonia. These congenital anomalies are consistent with a diagnosis of the Marden-Walker syndrome. The infant also had an omphalomesenteric duct, left hypoplastic kidney, hypoplastic right lower lobe of the lung, and displacement of the larynx to the right; these anomalies have not been described previously in this syndrome. A summary of the clinical manifestations of the previously reported patients is presented.     

A case of Marden-Walker syndrome with Dandy-Walker malformation

A 5-month-old girl with Marden-Walker syndrome is presented. This is a rare autosomal recessive syndrome. So far, approximately 20 cases have been described in the literature. The patient was hospitalized because of difficulty in feeding and slow spontaneous movements. Her parents were first cousins. She was diagnosed with clinical findings of growth and motor retardation, typical facial appearance, congenital heart disease, arachnodactyly, joint contractures, and a Dandy-Walker malformation on magnetic resonance imaging.     

Congenital myopathy with oculo-facial abnormalities (Marden-Walker syndrome)

Marden-Walker syndrome present in the neonatal period is characterized by oculo-facial abnormalities, congenital myopathy, and contractures. A newborn infant with a similar pattern of anomalies is reported, and further evidence for autosomal recessive inheritance as well as new neuropathological findings are included.     

A 26-month-old child with Marden-Walker syndrome and pyloric stenosis

We recently examined a 26-month-old boy with abnormal face, blepharophimosis, hypertelorism, apparently low-set ears, micrognathia, arachnodactyly, talipes equinovarus, and joint contractures. Subsequently he manifested failure to thrive, respiratory infections, and developmental delay. These congenital anomalies and associated findings are consistent with a diagnosis of the Marden-Walker syndrome. He also had mild pyloric stenosis and duodenal bands, not previously reported in this syndrome. This syndrome appears to be an autosomal recessive trait in some families. A summary of findings of the 16 previous published patients is presented.     

Marden-Walker syndrome: case report, literature review and nosologic discussion

Schrander-Stumpel C, de Die-Smulders C, de Krom M, Schyns-Fleuren S, Hamel B, Jaeken D, Fryns J-P. Marden-Walker syndrome: case report, literature review and nosologic discussion.
Clin Genet 1993: 43: 303–308. © Munksgaard, 1993
The Marden-Walker syndrome is characterized by psychomotor retardation, a mask-like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis and joint contractures. We report on a male patient with the clinical features of the syndrome. In addition, he had a Dandy-Walker malformation with hydrocephalus and vertebral abnormalities. During pregnancy, there were feeble fetal movements and polyhydramnios. We propose that Marden-Walker syndrome is one of the etiologic possibilities in children with the heterogeneous fetal a(hypo)kinesia deformation sequence (FADS). Differential diagnosis is discussed. The etiology is probably heterogeneous.     

Renal anomalies in Marden-Walker syndrome: A clue for prenatal diagnosis

Marden-Walker syndrome is an autosomal-recessive disorder characterized by psy-chomotor retardation, blepharophimosis, joint contractures, arachnodactyly, failure to thrive, and, infrequently, renal anomalies. We report on the prenatal diagnosis of Marden-Walker syndrome in a fetus which had had a previously affected sib with this syndrome. The ultrasonic findings indicative of the diagnosis in this fetus were in-trauterine growth retardation and renal cystic disease. We emphasize the importance of renal anomalies which, when present in combination with other ultrasound evidence of this syndrome, should be used as a clue for the diagnosis of Marden-Walker syndrome. © 1995 Wiley-Liss, Inc.     

Two brothers with the Marden-Walker syndrome: case report and review

Two brothers with blepharophimosis, congenital joint contractures, and mental retardation characteristic of the Marden-Walker syndrome are described. This sib pair strengthens the case for autosomal recessive inheritance of the syndrome.     

Marden-Walker phenotype: Spectrum of variability in three infants

The physical, radiographic, and pathologic findings in 3 new patients with Marden-Walker syndrome (MWS) are compared with those of previously described children with the syndrome. Over 75% of the children with MWS have blepharophimosis, psychomotor retardation, small mouth, micrognathia, kyphosis/scoliosis, and multiple contractures. Minimal diagnostic criteria have yet to be defined attesting to the broad range of variability and potential genetic heterogeneity in this disorder. © 1993 Wiley-Liss, Inc.     

The Dubowitz syndrome.

The Dubowitz syndrome is an autosomal recessive condition of intrauterine growth retardation, postnatal growth retardation, microcephaly, characteristic facial appearance, high-pitched hoarse voice, and borderline intelligence or mild mental retardation. Cleft palate may occur as well as hypospadias, cryptorchidism in affected males, and mild limb defects. The 13 cases reported in the European literature and eight personally examined patients are reviewed.     

The Coffin-Siris syndrome.

We report a white female infant with typical features of Coffin-Siris syndrome including thick eyebrows, flat nasal bridge, anteverted, wide nose tip, generalised hypertrichosis, scalp hypotrichosis, absence of the fifth fingernails and toenails, absence of the distal phalanges of the fifth fingers and of the second to fifth toes, small patellae, inguinal hernia, and sucking and feeding difficulties. There was decreased fetal activity and intrauterine growth retardation.