Neu-Laxova syndrome: report of a case from Turkey

Kuseyri F, Bilge I, Bilgiç L, Apak MY. Neu-Laxova syndrome: report of a case from Turkey.
Clin Genet 1993: 43: 267–269. © Munksgaard, 1993
We describe a case of Neu-Laxova syndrome in a newborn female who was born at full-term to consanguineous Turkish parents. The pathological and radiological features are described.     

Neu-Laxova syndrome: prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations.

A diagnosis of the Neu-Laxova syndrome (NLS) was made by ultrasonography at 32 wks of gestation. Ultrasonographic examination showed intrauterine growth retardation (IUGR), Dandy-Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of limbs. The findings in this case are consistent with NLS; however, they did not fit any of Curry's [1982] groups. Massive swelling of hands and feet were among the main manifestations in classic NLS cases. In the case presented herein, edema was noted only in the scalp. This might shed further light on the question of variability vs. heterogeneity in the NLS. This case shows the existing possibility of an early diagnosis of NLS and adds Dandy-Walker anomaly and choroid plexus cysts as new findings to this syndrome.     

An apparently new autosomal recessive syndrome with facial dysmorphism, macrocephaly, myopia and Dandy-Walker malformation

In this report we describe an apparently new MCA-MR syndrome with Dandy-Walker malformation in three severely mentally retarded siblings born to normal, non-consanguineous parents. In addition, they presented macrocephaly, facial dysmorphism, extreme myopia and brachytelephalangy with short and broad finger-nails.     

Oculocerebral syndrome with hypopigmentation (Cross syndrome): report of a new case

A syndrome of ocular and cutaneous hypopigmentation, severe mental retardation with spastic tetraplegia and athetosis was first observed by Cross in three siblings of an inbred Amish family. Since then, seven other patients, three sporadic and four with familial recurrence, have been reported in the literature, confirming the autosomal recessive inheritance. The clinical spectrum of the syndrome has been expanded to include true developmental defects of the CNS such as cystic malformation of the posterior fossa of the Dandy-Walker type. We report a new case of Cross syndrome.     

The Neu–Laxova syndrome in female sibs: Clinical and pathological features with prenatal diagnosis in the second sib

We report on affected sisters with the Neu–Laxova syndrome. Prenatal diagnosis of the condition was achieved by serial ultrasound examinations which demonstrated abnormal fetal growth in the second affected fetus before 24 weeks gestation.     

Dandy-Walker malformation in Ellis-van Creveld syndrome

We report on 2 Old Order Amish patients with Ellis-van Creveld (EvC) syndrome and the Dandy-Walker malformation; a similar case is noted in the literature. Pedigree analysis of our patients documents extensive inbreeding in successive generations. Considering the rarity of EvC syndrome and Dandy-Walker malformation as isolated malformations, the appearance of both in our 2 patients plus the patient in the literature suggests that Dandy-Walker malformation may be a manifestation in the EvC syndrome. However, in this isolate the coincidental occurrence of 2 rare recessive traits cannot be excluded.     

An autosomal recessive ectodermal dysplasia syndrome of hypotrichosis,onychodysplasia, hyperkeratosis,kyphoscoliosis, cataract,and other manifestations

We describe a 20-year-old woman with generalized trichodysplasia, dry skin with scaling, hyperchromic spots on limbs, hyperkeratosis (particularly intense on soles), dermatoglyphic abnormalities, onychodysplasia, shortness of stature, kyphoscoliosis, unusual facial appearance, minor malformations of limbs, bilateral nuclear cataract, narrow palpebral fissures, entropion, trichiasis, etc. The condition is probably due to an autosomal recessive gene. The patient is the only affected member in a sibship of four whose parents are second cousins.     

Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): Molecular genetics,clinical experience,and fetal morphology

Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases and has a high infant mortality. Prenatal diagnosis using fetal sonography can be unreliable, especially in early pregnancy. The ARPKD locus has been mapped to proximal chromosome 6p allowing haplotype-based prenatal diagnosis in “at-risk” families. From December 1994 to March 1997, we received 258 inquiries regarding prenatal evaluation and we have completed analyses in 212 families. To date, 65 prenatal analyses have been performed in 57 families. In the majority of the requesting families (45/57), the index children are deceased and their DNA was extracted from paraffin-embedded tissue. Eighteen fetuses were homozygous for the disease-associated haplotypes. In 12 of these fetuses, pathoanatomical examination demonstrated typical ARPKD changes consisting of dilated collecting ducts and the characteristic hepatic ductal plate malformation. These changes were detected in two fetuses as early as 13 weeks gestational age. These cases represent the earliest demonstration of ARPKD-associated histopathology reported to date. One high risk fetus was carried to term and turned out to be unaffected. However, the diagnosis of ARPKD remained doubtful in the index patient. Forty-three fetuses were either heterozygous or homozygous for a nondisease-associated haplotype and all infants born were phenotypically unaffected at birth. In four cases, a recombination event occurred between the flanking markers and no genotypic prediction was possible. Three of these pregnancies were terminated and necropsy of the fetuses confirmed ARPKD, while one fetus was carried to term and showed no abnormalities at birth. These results show that haplotype-based prenatal testing is feasible and reliable in pregnancies “at risk” for ARPKD. An absolute prerequisite for these studies is an accurate diagnosis of ARPKD in previously affected sib(s). Am. J. Med. Genet. 76:137–144, 1998. © 1998 Wiley-Liss, Inc.     

Prenatal diagnosis of cystic kidney disease with ventriculomegaly: A report of six cases in two related sib ships

In 2 consanguineous relationships, a Cape Verdian man fathered six fetuses (5 male) with fetal ventriculomegaly and echodense fetal kidneys as visualized by ultrasonography between 16 and 32 weeks. During prenatal monitoring, an increased alpha fetoprotein level and abnormal acetyl-cholinesterase were detected at amniocentesis in 5 of 6 affected fetuses. Chromosomes were normal. Five pregnancies resulted in elective termination; one child was still-born prematurely. Hydrocephalus and cystic disease of the (renal) cortico medullary areas were found. One fetus had polydactyly. The differential diagnosis and prenatal diagnosis of this presumably autosomal recessive syndrome are discussed.     

Prenatal diagnosis of the prune belly syndrome

A male fetus with prune belly syndrome was diagnosed by ultrasound at 30 weeks of gestation. The diagnosis was confirmed after birth.     

Two sisters with clinical diagnosis of Wiskott-Aldrich syndrome: Is the condition in the family autosomal recessive?

We report two sisters in a family representing manifestations of Wiskott-Aldrich syndrome' (WAS), an X-linked immunodeficiency disorder. An elder sister had suffered from recurrent infections, small thrombocy-topenic petechiae, purpura, and eczema for 7 years. The younger sister had the same manifestations as the elder sister's for a 2-year period, and died of intracranial bleeding at age 2 years. All the laboratory data of the two patients were compatible with WAS, although they were females. Sialophorin analysis with the selective radioactive labeling method of this protein revealed that in the elder sister a 115-KD band that should be specific for sialophorin was reduced in quantity, and instead an additional 135-KD fragment was present as a main band. Poly-merase chain reaction (PCR) analysis of the sialophorin gene and single-strand conformation polymorphism (SSCP) analysis of the PCR product demonstrated that there were no detectable size-change nor elec-trophoretic mobility change in the DNA from both patients. The results indicated that their sialophorin gene structure might be normal. Studies on the mother-daughter transmission of X chromosome using a pERT84-MaeIII polymorphic marker mapped at Xp21 and HPRT gene polymorphism at Xq26 suggested that each sister had inherited a different X chromosome from the mother. Two explanations are plausible for the occurrence of the WAS in our patients: the WAS in the patients is attributable to an autosomal gene mutation which may regulate the sialophorin gene expression through the WAS gene, or, alternatively, the condition in this family is an autosomal recessive disorder separated etiologically from the X-linked WAS. © 1995 Wiley-Liss, Inc.     

Marden—Walker syndrome versus isolated distal arthrogryposis: Evidence that both conditions may be variable manifestations of the same mutated gene

In this report we present evidence that Marden-Walker syndrome and isolated distal arthrogryposis may be variable manifestations of the same entity.
We describe the clinical and pathological findings in two affected siblings, the first two children of normal, non-consanguineous parents. The first child, a female, presented a typical Marden–Walker syndrome with Dandy–Walker type CNS malformation, corpus callosum hypoplasia and enlarged ventricles. In the second pregnancy, echographic examination revealed joint contractures of the hands and feet. Feto-pathological examination revealed a normocephalic male fetus with severe distal arthrogryposis. There was no facial dysmorphism and pathological examination of the brain, the spinal cord and muscle was normal.     

Congenital cutis laxa with ligamentous laxity and delayed development, Dandy-Walker malformation and minor heart and osseous defects

We present a female infant exhibiting congenital cutis laxa with retardation of growth and motor development, ligamentous laxity and congenital dislocation of the hips. This connective tissue disorder was associated with Dandy-Walker malformation, atrial and ventricular defect and minor bone abnormalities including multiple wormian bones, abnormal tubulation of long bones and absent twelfth pair of ribs. This association is believed to be unique.     

The Floating-Harbor syndrome: two affected siblings in a family

In this report we describe two siblings with pre-and postnatal growth retardation and clinical signs and symptoms most compatible with the diagnosis of Floating-Harbor syndrome. The oldest sibling, a girl, died in the first year of life from recurrent infections. The younger sibling, a male, is now 16.5 years old and mildly mentally retarded.     

Prenatal growth retardation, microphthalmos/iris coloboma, cloudy cornea, urogenital anomalies and microcephaly. A possible new sublethal syndrome

We present the findings of a "new" sublethal MCA syndrome in three siblings, one female and two boys, the only children of healthy, non-consanguineous parents. In addition to prenatal growth retardation and early demise, they presented the same pattern of multiple malformations: relative microcephaly with bird-headed face, microphthalmos/coloboma iris/cloudy corneae, genital anomalies with hypospadias and cryptorchidism in the two males. Associated anomalies included: cardiac defects (2/3), unilateral cleft lip/cleft palate (1/3), anal stenosis (2/3) and unilateral renal agenesis (1/3).     

A new short rib syndrome: Report of two cases

We describe two unrelated malformed infants who died shortly after birth and who had multiple congenital anomalies including hydrops and ascites, facial abnormalities (with median cleft of the upper lip), narrow thorax, protuberant abdomen, and short, bowed limbs. Postmortem radiographs showed very short ribs and disproportionately short long tubular bones; no metaphyseal abnormalities were present. Comparison with earlier described short-rib/short-rib-polydactyly syndromes suggest that the disorder present in our two cases is a new type of short-rib syndrome. One of our patients was born to a consanguineous couple; in a subsequent pregnancy, real-time ultrasonography in the second trimester showed that the female fetus had the same abnormalities as its sib. Diagnosis was confirmed after elective abortion. This suggests that this short-rib syndrome may be an autosomal recessive disorder.     

Hutchinson-Gilford progeria syndrome: report of a Libyan family and evidence of autosomal recessive inheritance

A Libyan family with the Hutchinson-Gilford progeria syndrome affecting three children of two sisters is described. The proband was ascertained because of repeated unhealing fractures. The pattern of inheritance appeared autosomal recessive.     

Familial Dandy-Walker malformation associated with macrocephaly,facial anomalies,developmental delay,and brain stem dysgenesis: Prenatal diagnosis and postnatal outcome in brothers. A new syndrome?

Brothers are reported with an apparently new constellation of manifestations including Dandy-Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X-linked recessive. An extensive review of the differential diagnosis of DWC is provided. © 1994 Wiley-Liss, Inc.     

Animal models: Prenatal diagnosis of Chediak-Higashi syndrome in the cat by evaluation of cultured chorionic cells

The autosomal recessive disease Chediak-Higashi syndrome (CHS) is a progressive and generally fatal disease of humans. The under lying genetic defect in CHS is unknown and prenatal diagnostic methods have not been applied to this disease. The purpose of this study was to determine if CHS chorionic cells expressed a characteristic of CHS—enlarged lysosomes—that would permit the prenatal diagnosis of the disease. Cats with CHS, which have been shown to be homologous with human CHS, were used as the model system in this study. Chorionic tissue samples were obtained from CHS and control cat fetuses and cultures of cells were established. Acid phosphatase was utilized as a marker of lysosomes and cultures of chorionic fibroblasts from CHS and control fetuses were stained histochemically for acid phosphatase. The diameter of the largest lysosomes in 150 cells of each fetus was determined. The mean (±SD) diameter (in μm) of the largest lysosomes of normal fetuses was 0.9 ± 0.13 (range 0.5–7.0 μm), whereas the mean diameter of lysosomes in CHS chorionic cells was 3.9 ± 0.65 μm (range 0.5–25 μm). These means were significantly different (P < 0.0001). These data suggest that it should be possible to diagnose human CHS in the first trimester by chorionic villus sampling.     

Microcephaly,microphthalmia, congenital cataract,optic atrophy,short stature,hypotonia, severe psychomotor retardation,and cerebral malformations: a second family with micro syndrome or a new syndrome?

We report on four children of both sexes from a highly inbred family with hypotonia, spastic diplegia, microcephaly, microphthalmia, congenital cataract, optic atrophy, ptosis, kyphoscoliosis, short stature, severe mental retardation, and cerebral malformations. Six other children may also have been affected. The differential diagnosis and the possibility of a second family with the micro syndrome are discussed.