Orofaciodigital Syndrome VI

Alternative Names

  • Oral-Facial-Digital syndrome, Type VI
  • OFDS VI
  • Varadi-Papp Syndrome
  • Varadi Syndrome
  • Polydactyly, Cleft Lip/Palate or Lingual Lump, and Psychomotor Retardation
Back to search Result
WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

277170

Mode of Inheritance

Autosomal recessive

Description

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.

Molecular Genetics

In the mouse the homeobox containing Engrailed gene (En-1) is specifically expressed across the midbrain-hindbrain junction, the ventral ectoderm of the limb buds, and in regions of the spinal cord. Mice homozygous for a mutation in this gene die within a day of birth and have multiple abnormalities. These include abnormally shaped forelimbs (postaxial digit and digit fusion) and absent cerebellum, colliculi, and third and fourth cranial nerves in the midbrain. The homologous human EN-1 gene is expressed mainly in the cerebellar vermis and deep cerebellar nuclei of the midgestation human fetus. The DNA sequence is highly conserved between the mouse En-1 and human EN-1 genes and thus the genes could be functionally similar in the two species.

Epidemiology in the Arab World

View Map

Other Reports

Egypt

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. 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.  Al-Gazali and colleagues indicated that these cases may represent a new autosomal recessive midline defect syndrome with features overlapping orofaciodigital syndrome type VI.

Kuwait

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.]

Saudi Arabia

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.

© CAGS 2022. All rights reserved.