The oral-facial-digital syndromes are a group of heterogeneous genetic disorders having in common facial anomalies, oral abnormalities, and digital malformations. Varadi-Papp syndrome, or oral-facial-digital syndrome type VI, is a rare autosomal recessive disorder distinguished from other oral-facial-digital syndromes by metacarpal abnormalities with central polydactyly and cerebellar malformations, mainly vermis aplasia/hypoplasia. Other findings include renal agenesis or dysplasia, highly arched/cleft palate, tongue clefts, tongue nodules, hyperplastic frenula, cleft lip, and broad nasal tip.
Al-Gazali et al. (1999) reported two sibs with features overlapping those of orofaciodigital syndrome type VI (Varadi-Papp syndrome). The parents were unrelated Egyptians of normal phenotypes, who were residents of the United Arab Emirates. The second child of the couple had dysmorphic features which included antimongoloid slant of the palpebral fissures, unilateral choanal atresia with absent nasal sputum, low set ears, bilateral undescended testes, and a small phallus. The baby died at 36 hours of age of undetermined cause. On the other hand, the two surviving patients (a female and a male) presented at birth with oculomotor abnormalities, dysmorphic facial features, and dysgenesis of the cerebellar vermis. The oculomotor abnormalities in the patients were suggestive of third nerve paralysis, which was unilaterall in the elder sister and bilateral in the younger brother. There were minimal oral manifestations (high arched palate) in both of them and one had postaxial polydactyly of both hands and one foot. In addition, there was evidence of aplasia of the pituitary gland on MRI scan in both of them with evidence of hypopituitarism. Both responded well to hormone replacement therapy with improvement in their linear growth and mental ability. Al-Gazali and colleagues indicated that these cases may represent a new autosomal recessive midline defect syndrome with features overlapping orofaciodigital syndrome type VI.
Sabry et al. (1997) reported the case a Bedouin boy suffering from multiple congenital abnormalities/mental retardation (MCA/MR). The subject was born with a birth weight of 3,300g to second cousin healthy parents with four healthy children and one stillborn boy who experienced unspecified multiple congenital abnormalities. The patient underwent feeding difficulty, tongue lobules/nodules, postaxial polydactyly of the left hand, "central" polydactyly of the right hand, and corpus callosum hypoplasia which were similar features of Varadi-Papp syndrome (OFD VI). Furthermore, the subject experienced the occurrence of ridged metopic suture, retarded global development and the occurrence of a small nose with depressed nasal bridge which overlaps with Optiz trigonocephaly (C Syndrome). Sabry et al. (1997) concluded that the common features among OFD VI and C Syndrome consisted of small penis and testes, short stature/failure to thrive, strabismus, ear abnormality, and hypotonia.
Abu-Henedi et al. (2001) described a 2.5 year old Kuwaiti boy suffering from unusual facial features, psychomotor retardation, limb malformations and other abnormalities analogous to Varadi-Papp syndrome. The subject was born with a birth weight of 4.0kg to healthy consanguineous parents with the father aged 26 years and the mother 24 years, he was the third sibling after two healthy girls. The patient suffered from central polydactyly with Y-shaped exterior of the third metacarpal bone of both hands and reduplicated halluces which were revealed through hand/feet radiography. He also experienced cerebellar vermis hypoplasia, dilatation of cerebral ventricles, and large ostium primum (ASD). Chromosomal analysis was employed and revealed normal male karyotype (46, XY). Abu-Henedi et al. (2001) concluded that the patients' phenotype is greatly related to Varadi-Papp Syndrome (OFD-VI).
[Abu-Henedi MM, Al-Awadi SA, Bastaki L, Al-Naggar RL. Varadi-Papp syndrome (OFD-VI) in a Kuwaiti boy. Egyptian J Med Human Genet. 2001; 2(2):59-62.]
Al-Qattan and Hassanian (1997) described a patient with clinical features consistent with both orofaciodigital syndrome type I (Papillon Leage-Psaume syndrome) and type VI (Varadi-Papp syndrome). The palmar/nail abnormality in the patient was associated with loss of active flexion of the interphalangeal joints. However, a careful review of the radiological findings in the hands placed the final diagnosis as a new mutation of orofaciodigital syndrome type I.
[See: Egypt > Al-Gazali et al., 1999].