Fine-Lubinsky syndrome: sibling pair suggests possible autosomal recessive inheritance

In 1983, Fine and Lubinsky reported a single patient with craniofacial anomalies, hearing loss, cataracts, microstomia, CNS anomalies, and developmental delay. Since that time, three additional patients with similar findings have been described. In each case the patients was the only affected child in his or her family. Here we describe the first brother and sister sibling pair with features suggestive of Fine-Lubinsky syndrome. Features present in one or both of our patients, and the majority of previously described individuals with Fine-Lubinsky syndrome, include: craniosynostosis/abnormal calvaria, prominent frontal bones, flat facial profiles, small noses, microstomia, hearing loss, developmental delay/mental retardation, and abnormal digits. Unusual anomalies present in our patients include marked brachydactyly of fingers and toes, camptodactyly most severely affecting the second fingers, and permanence of decidual teeth. The identification of a sibling pair with Fine-Lubinsky suggests a possible autosomal recessive inheritance pattern. It is important that parents of children with Fine-Lubinsky be informed of the increased recurrence risk associated with that type of inheritance.     

Evidence for autosomal recessive inheritance in cerebral gigantism

Three cases of cerebral gigantism, two sibs and their double first cousin, are described in a large inbred family from Israel. Two of the three were observed and diagnosed at birth and two were followed for two years. They all presented the signs and symptoms considered typical of this syndrome, as well as some of the less frequent findings. Generalized oedema and flexion contractures of the feet were observed in two of the three at birth. This has not hitherto been reported in cases of cerebral gigantism, of whom only a few have been observed and diagnosed at birth. Autosomal recessive inheritance is clearly implied in this family.     

The autosomal recessive mode of inheritance of C1 r deficiency in a large Puerto Rican family

All living members of three generations of a large family with C1 r deficiency were studied. The two index cases showed undetectable C1 r and partial deficiency of C1 s associated with cutaneous, renal and joint disease as described previously (Moncada et al., 1972). The quantitative C1 q, C1 r and C1 s studies on the parents and the normal siblings were consistent with an autosomal recessive mode of inheritance for the C1 r trait.

There was more corrleation of the C1 r levels with the C1 s levels than with the C1 q levels, compatible with a linkage of the synthesis or catabolism of C1 s with C1 r.

     

Gonadal mosaicism as a rare cause of autosomal recessive inheritance

Autosomal recessive diseases are typically caused by the biparental inheritance of familial mutant alleles. Unusual mechanisms by which the recessiveness of a mutant allele is unmasked include uniparental isodisomy and the occurrence of a de novo chromosomal rearrangement that disrupts the other allele. Gonadal mosaicism is a condition in which a postfertilization mutation is confined to the gamete precursors and is not detected in somatic tissues. Gonadal mosaicism is known to give the impression of autosomal recessive inheritance when recurrence of an autosomal‐dominant condition among offspring of phenotypically normal parents is observed. Here, we report an extremely rare event in which maternal gonadal mosaicism for a recessive mutation in COL4A4 caused the recurrence of Alport syndrome within a consanguineous family. Such rare occurrence should be taken into account when analyzing pedigrees both for clinical and research purposes.     

Additional case of opsismodysplasia supporting autosomal recessive inheritance

The authors describe clinical and radiological findings in a 2-year-old boy from consanguineous parents. A diagnosis of opsi(s)modysplasia (=delayed maturation) had been made (MIM 258480). The purpose of this paper is to draw attention to the striking radiological manifestations. Consanguinity in the parents of our case and occurrence in a brother and sister in a previous report support an autosomal recessive transmission. © 1994 Wiley-Liss, Inc.     

Evidence for autosomal recessive inheritance of costovertebral dysplasia

Hereditary costovertebral dysplasia was ascertained in five children of two related sibships in a pattern consistent with autosomal recessive inheritance. Clinical and radiological studies showed abnormalities limited to the axial skeleton and ribs. Genetic heterogeneity, evident from the fact that an indistinguishable disorder has been reported as dominant, is important in relation to genetic counseling. A phenocopy caused by teratologic agents should also be considered, since the same malformation has been produced in experimental mammals.     

Catel-Manzke syndrome: a clinical report suggesting autosomal recessive inheritance

We describe a 3-month-old male infant with cleft palate, glossoptosis, micrognathia, and bilateral clinodactyly, an association which is characteristic of Catel-Manzke syndrome. In addition, the patient had ligamentous laxity in the knee which is a rare finding of this syndrome. The mode of inheritance of Catel-Manzke syndrome is unknown. Most cases are thought to be sporadic but the present patient with consanguinity between the parents and a possibly affected sib provide support for autosomal recessive inheritance.     

Elsahy-Waters syndrome: Evidence for autosomal recessive inheritance

Elsahy-Waters or branchioskeletogenital syndrome is a rare MCA/MR syndrome characterized by moderate mental retardation, hypospadias and characteristic craniofacial morphology, which includes brachycephaly, facial asymmetry, exotropia, hypertelorism/telechantus, broad nose, concave nasal ridge, underdeveloped midface, prognathism, and radicular dentin dysplasia. Here we report on a 44-year-old woman and her 45-year-old brother, born to consanguineous parents, who show a striking resemblance to the earlier described patients. The hitherto reported patients were male and in one pedigree parents were consanguineous. The present report of an affected woman and her brother, born to consanguineous parents, supports autosomal recessive inheritance of this condition. We provide a short review of all previously reported patients with Elsahy-Waters syndrome and related entities.     

The Aarskog syndrome in a large family, suggestive for autosomal dominant inheritance

A large family in which the Aarskog syndrome is transmitted in three generations was studied. In affected males, a large variability of expression was observed, while females show minor signs only. However it is sometimes possible to identify individual females as carriers. The observation of male to male transmission and the absence of symptoms in some daughters of affected male persons suggest a sex-influenced autosomal inheritance in this family. This may suggest heterogeneity in the Aarskog syndrome, since in most families described an X-linked recessive mode of inheritance was indicated.     

Choanal atresia: Evidence for autosomal recessive inheritance

Three individuals with choanal atresia were born in an inbred kindred. This report shows that nonsyndromal choanal atresia can be transmitted as an autosomal recessive trait. © 1992 Wiley-Liss, Inc.     

Frontofacionasal dysplasia: evidence for autosomal recessive inheritance

We report on a 2-month-old girl whose parents are first cousins. The patient has severe craniofacial anomalies characterized by: encephalocele, hypertelorism, midface hypoplasia, hypoplasia of frontal bone on the left side, malformed left eye, absent inner eyelashes, irregular S-shaped palpebral fissures, deformed nostrils, hypoplastic right nasal wing and cleft lip, and clefts of premaxilla, palate and uvula. No other malformations were observed. This association of anomalies suggests the diagnosis of frontofacionasal dysplasia. Parental consanguinity suggests autosomal recessive inheritance.     

Uncomplicated familial hypospadias: evidence for autosomal recessive inheritance

Uncomplicated hypospadias was found in eight members of a large, consanguineous Bedouin family. Virilization and fertility were normal in the only postpubertal individual. The inheritance is most likely autosomal recessive and we suggest that in some of the familial cases in which polygenic or multifactorial inheritance was previously proposed, homozygosity for recessive genes may be responsible for the increased risk to siblings. Dominantly transmitted hypertelorism with diastema was an independent and coincidental finding in this family.     

Choanal atresia: evidence for autosomal recessive inheritance.

Three individuals with choanal atresia were born in an inbred kindred. This report shows that nonsyndromal choanal atresia can be transmitted as an autosomal recessive trait.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome: confirmation of autosomal recessive inheritance.

We report two female sibs with the megacystis-microcolon-intestinal hypoperistalsis syndrome. The parents are first cousins. These cases, together with three other published reports of affected sibs, confirm the autosomal recessive inheritance of the syndrome.     

A novel oculo-oto-facial dysplasia in a Native Alaskan community with autosomal recessive inheritance

We describe a novel autosomal recessive malformation syndrome in four related individuals from a geographically isolated Native Alaskan community, who have facial defects similar to those of individuals with Treacher Collins (TCS) and Miller syndrome. Distinctive findings include malar and mandibular hypoplasia, lower eyelid coloboma, choanal atresia, orofacial clefting, and external ear malformation with preauricular tags. Intellect is normal and profound mixed hearing loss has been observed in affected adults. Variable extracranial findings include atrioseptal defect, renal dysplasia, and imperforate anus, however, no limb defects have been observed. Cranial imaging studies demonstrate relative prominence of the zygoma, inferior orbital maxillary hypoplasia, and lateral orbital wall defects with an accessory superior bony projection off the zygoma lateral to the orbital rim. We propose that these individuals have inherited a novel autosomal recessive condition we have termed oculo-oto-facial dysplasia (OOFD) with unique radiographic findings.     

Two new cases of Cumming syndrome confirming autosomal recessive inheritance

We report on two stillborn sisters with generalized hydrops, campomelia, cervical lymphocele, and polycystic dysplasia of kidney, liver, and pancreas. This syndrome conforms to that first described by Cumming et al. [Am. J. Med. Genet. 25:783-790, 1986]. This observation provides additional support for the notion that this syndrome has an autosomal recessive pattern of inheritance.