69 Oro-facio-digital Syndrome, Type I
Oro-facio-digital Syndrome, Type I 785
OFD1, oral-facial-digital syndrome type I, Papillon-Leage/Psaume syndrome
Flat midface, thin nose, short upper lip/midline cleft, lobulated tongue, digital anomalies, mental retarda- tion
Frequency: 1 in 50,000 births. Over 250 cases record- ed.
Genetics
Most cases sporadic; X-linked dominant (OMIM 311200), disease-gene, OFD1 (formerly named Cxorf5/71–7a), maps to Xp22.2–22.3; lethal in hem- izygous males.
Clinical Features
• Flat midface
• Lateral displacement of inner canthi
• Broad nasal root, thin nose, lack of nasal alar flare, small nostrils
• Short upper lip, small midline pseudocleft, lobu- lated tongue, tongue hamartomas, ankyloglossia, multiple hyperplastic oral frenula, cleft palate, absent lateral incisors
• Hypoplasia of the mandible
• Brachydactyly, syndactyly, clinodactyly, postaxial polydactyly, preaxial polysyndactyly of the hallux
• Variable mental retardation
• Milia, dry skin, alopecia of the scalp
• Polycystic kidneys
• CNS anomalies Differential Diagnosis
• Other oro-facio-digital syndromes
Radiographic Features Skull
• Increased nasion-sella-basion angle (on average 144°, normal value 131°)
• Malposition of the teeth
• Microcephaly, frontal bossing
• Short mandible Extremities
• Clinodactyly
• Syndactyly
• Brachydactyly
• Camptodactyly
• Adactyly
• Cone-shaped epiphyses
• Polysyndactyly of the hallux (unilateral)
• Irregular reticulated areas of radiolucency in the shaft of the bones
• Irregular mottling of metacarpals and phalanges
• Metaphyseal rarefaction
• Shortness of tubular bones Generalized Bone Defects
• Osteoporosis
• Irregular mineralization of hand and foot bones
Bibliography
Anneren G, Arvidson B, Gustavson KH, Jorulf H, Carlsson G.
Oro-facio-digital syndromes I and II: radiological methods for diagnosis and the clinical variations. Clin Genet 1984;
26: 178–86
Baraitser M. The orofaciodigital (OFD) syndromes. J Med Genet 1986; 23: 116–9
Feather SA, Woolf AS, Donnai D, Malcolm S, Winter RM. The oral-facial-digital syndrome type 1 (OFD1), a cause of polycystic kidney disease and associated malformations, maps to Xp22.2-Xp22.3. Hum Mol Genet 1997; 6: 1163–7 Ferrante M, Giorgio G, Feather SA, Bulfone A, Wight V, Ghiani
M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Odent S, Le Marec B, Malcolm S, Winter R, Ballabio A, Franco B. Identi- fication of the gene for oral-facial-digital type I syndrome.
Am J Hum Genet 2001; 68: 569–76
Gorlin RJ, Psaume J. Orodigitofacial dysostosis – a new syn- drome. J Pediatr 1962; 61: 520–30
Odent S, Le Marec B, Toutain A, David A, Vigneron J, Treguier C, Jouan H, Milon J, Fryns JP, Verloes A. Central nervous system malformations and early end-stage renal disease in oro-facio-digital syndrome type I: a review. Am J Med Genet 1998; 75: 389–94
Salinas CF, Pai GS, Vera CL, Milutinovic J, Hagerty R, Cooper JD, Cagna DR. Variability of expression of the orofaciodigi- tal syndrome type I in black females: six cases. Am J Med Genet 1991; 38: 574–82
Toriello HV. Heterogeneity and variability in the oral-facial- digital syndromes. Am J Med Genet (Suppl) 1988; 4: 149–59 Toriello HV. Oral-facial-digital syndromes, 1992. Clin Dysmor-
phol 1993; 2: 95–105
Vaillaud JC, Martin J, Szepetowski G, Robert JM. Le syndrome oro-facio-digital. Etude clinique et génétique à propos de 10 cas observés dans une même famille. Rev Pediatr 1968; 4:
383–92
O
Oro-facio-digital Syndrome, Type I 786
Fig. 69.1 a, b. Patient 1, 7 months. a Tongue is lobulated, with a small hamartoma protruding from its left anterior border.
Note also small midline cleft, short upper lip, absence of later- al incisors, and broad nasal root with thin nose and lack of nasal alar flare. b Osseous and cutaneous syndactyly of fingers
3 and 4, and cutaneous syndactyly of fingers 4 and 5. Hand is brachydactylous, with prominent shortening of the 1st and 2nd digit. (Courtesy of Dr. M.C. Digilio, Ospedale Bambino Gesù, Rome)
a b
Fig. 69.2. Patient 2, 2 weeks. The characteristic reticular pat- tern of radiolucencies and spicule-like formation is evident on the metacarpals and phalanges in this child. (Reprinted, with permission, from Anneren et al. (1984)
