Joint dislocation and cerebral anomalies are consistently associated with oral-facial-digital syndrome type IV

We present a female patient with the oral-facial-digital syndrome type IV. Our report, the tenth in the literature, describes the typical manifestations of the syndrome, combined with malformations and deformations which have not always been described in the previously reported cases. They include cerebral and renal anomalies, anal atresia and dislocation of elbows and knees.     

Possible new type of oral-facial-digital syndrome with retinal abnormalities: OFDS type (VIII)

The most recent classification of the oral-facial-digital syndromes (OFDS) includes 7 types distinguishable by different clinical signs. We describe 2 brothers presenting oral, facial, and digital anomalies and an additional manifestation consisting of specific retinal abnormalities, i.e., retinochoroideal lacunae of colobomatous origin. Our patients may be affected with a new type of OFDS, i.e., OFDS type VIII, characterized by eye abnormalities in addition to other manifestations that partially overlap with those of OFDS type II. Given that there are 2 affected brothers, we cannot distinguish between autosomal and X-linked recessive inheritance.     

Discordance of oral-facial-digital syndrome type 1 in monozygotic twin girls.

The oral-facial-digital syndrome type 1 (OFD1) includes limb, facial, intraoral malformations and the gene for the disorder was recently mapped to Xp22.3-p22.2. We report on monozygotic twin girls discordant for OFD1. Monozygosity is supported by placental pathology (monochorionic diamniotic) and molecular studies with probability of dizygosity <1 x 10(-6). The affected twin has oral cavity abnormalities including median cleft lip, cleft palate, lobulated hamartomatous tongue, aberrant hyperplastic oral frenula, alveolar notches, and absent lateral incisors. Facial manifestations include telecanthus, hypoplastic alae nasi, and transient neonatal facial milia. The patient also has short and deviated fingers with partial cutaneous syndactyly. At 10 years, she has not had central nervous system or kidney problems. X-inactivation study revealed similar X-inactivation patterns in the lymphoblasts of both twins. We conclude that skewed X-inactivation is an unlikely cause for the discordance, which is more likely due to a postzygotic mutation in the affected twin.     

Polycystic kidney disease in a patient with the oral-facial-digital syndrome - type I.

Bilateral polycystic kidneys and chronic renal failure were observed in a 48-year-old woman with the classic clinical features of the oral-facial-digital syndrome, Type I (OFD-I). Since this association has been previously reported in two other patients, these findings suggest that polycystic kidneys may be a hitherto unrecognized manifestation of the oral-facial-digital syndrome.     

Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome.

The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a large deletion at 17q11.2, encompassing the entire NF1 gene. The other symptoms in the two cases were similar to the features reported in Weaver syndrome. Although the combination of NF1 and an overgrowth syndrome resembling Weaver syndrome in this family may be fortuitous, we favour the hypothesis that the deletion of the entire gene has caused this combined phenotype. Possible pathogenetic mechanisms are discussed. The observation suggests a relation between NF1 with an extraordinarily large gene deletion and a Weaver(-like) syndrome. This warrants investigation for deletions in the 17q11.2 region in Weaver(-like) syndrome patients.     

Otopalatodigital syndrome type II associated with omphalocele: Report of three cases

We present 3 patients with otopalatodigital (OPD) syndrome type II and omphalocele; 2 of the cases are brothers. There are now 6 known cases of OPD type I or II with omphalocele. We propose that this combination is not co-incidental and discuss mechanisms that may result in the combination of OPD, omphalocele, and other midline defects. © 1993 Wiley-Liss, Inc.     

Intracardiac epithelial cyst in association with an atrioventricular canal defect

An epithelial cyst within the heart is an uncommon occurrence. Cysts associated with cardiac malformations are very rare. We present a case of an epithelial cyst in the interatrial septum of a premature infant in association with a persistent atrioventricular canal defect.     

On lumping and splitting: a fetus with clinical findings of the oral-facial-digital syndrome type VI, the hydrolethalus syndrome, and the Pallister-Hall syndrome.

The three midline malformation complexes, the oral-facial-digital syndrome type VI (OFDS VI) or Váradi syndrome, the hydrolethalus syndrome (HS), and the Pallister-Hall syndrome (PHS) have been described as distinct genetic entities. Here, we report a fetus with a combination of clinical findings of all 3 syndromes similar to the twin fetuses described in the accompanying paper (Hingorani et al., 1991). The phenotypic overlap in these fetuses with the OFDS VI, HS, and PHS raises the question as to whether or not they indeed represent separate genetic entities as previously assumed.     

Hypothalamic hamartoma in oral-facial-digital syndrome type VI (Váradi syndrome)

Oral-facial-digital syndrome (OFDS) type VI (Váradi syndrome) is an autosomal recessive trait of orofacial anomalies, cerebellar dysgenesis, and polysyndactyly. Developmental anomalies of the posterior fossa, including cerebellar hypoplasia and variants of the Dandy-Walker complex, are the most common central nervous system malformations reported in patients with this syndrome. We report hypothalamic hamartoma, supernumerary maxillary incisor, and precocious puberty in a boy with OFDS type VI. We propose that hypothalamic hamartoma is an occasional manifestation of OFDS type VI. © 1994 Wiley-Liss, Inc.     

Nonrandom association of atrioventricular canal and del (8p) syndrome.

We describe a patient with partial deletion of the short arm of chromosome 8 with an atrioventricular canal. This type of congenital heart defect was found in 4 of the 7 previously reported del (8p) children with a congenital heart defect in which the cardiac assessment was complete. The prevalence of an atrioventricular canal in this aneuploidy is high and suggests a nonrandom association of the 2 anomalies.     

Six patients with oral-facial-digital syndrome IV: The case for heterogeneity

The oral-facial-digital syndromes (OFDS) have in common minor facial and oral anomalies (including tongue lobulation and/or hamartomas, accessory frenula, and alveolar anomalies) and variable digital defects such as polydactyly. The classification based on the presence of additional findings [Toriello, 1988, 1993] is not perfect, as many reported examples of a particular OFDS have some other condition. Here we describe six children, all diagnosed as having OFDS IV (OFDS with tibial defects), whose manifestations illustrate the apparent genetic heterogeneity. Am. J. Med. Genet. 69:250–260, 1997. © 1997 Wiley-Liss, Inc.     

Oral-facial-digital syndrome VII is oral-facial-digital syndrome I: a clarification

We report on further clinical findings in the one single family in the literature classified as oral-facial-digital (OFD) type VII in order to demonstrate that the diagnosis in this kindred should, in fact, be OFD type I. The mother and the daughter described in the original report have since developed polycystic kidney disease. In addition, the daughter recently had a daughter of her own with central nervous system, oral and digital anomalies. Linkage studies have shown that all the affected women share the same haplotype across the previously identified region Xp22.2p22.3 to which OFD I maps. Although the pedigree was too small for a significant lod score, the combination of clinical and molecular information clearly shows that the disease in this family is OFD I. We report this family in order to clarify and simplify the classification of the oral-facial-digital syndrome spectrum and to recommend the removal of OFD VII from the classification system of the oral-facial-digital syndromes.