A 30-year-old otherwise healthy woman gave birth to a full-term girl with a midline cleft lip. The mother denied any drug exposure or viral illness during pregnancy. Her family history was significant for midline cleft lip in a maternal great aunt.
At birth, the infant weighed 3,954 g and had a head circumference of 35 cm. The patient had Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. Physical examination results were remarkable for sacral dimple, a 2-vessel umbilical cord, umbilical hernia, and an incomplete midline cleft lip with a 2 cm mucosal tag at the frenulum. Despite the cleft lip and mucosal tag, the baby was able to breastfeed.
Results of basic laboratory studies, including complete blood count, complete metabolic panel, and neonatal screening, were normal. Head ultrasonography results showed ventriculomegaly but no signs of bleeding. Results of abdominal ultrasonography were normal. The patient was discharged home 3 days later.
At the 1-week follow-up visit, the patient was doing well and continued to breastfeed exclusively. Physical examination showed no change in her cleft lip and mucosal tag. The patient was referred to plastic surgery for repair of her cleft lip and to genetics for testing for genetic abnormalities.
A week later, the patient was seen in the clinic for poor weight gain. The infant had gained only 1 pound in 1 week. The mother denied feeding difficulties, vomiting, or diarrhea in the child. Magnetic resonance imaging of the brain revealed agenesis of the corpus callosum with associated colpocephaly of approximately 3 mm. A thyroglossal duct cyst was seen at the base of the girl’s tongue. Genetic testing results revealed duplication of the short stature homeobox (SHOX) gene.
Based on the family history, physical examination findings, and genetic test results, the patient received a diagnosis of oral-facial-digital syndrome type I (OFD I). Given her family history, an X-linked dominant pattern of inheritance is likely.
OFD I is a rare, X-linked genetic disorder with an estimated annual incidence of 1 in 250,000 live births.1 The condition is lethal in males and results from de novo in utero mutation of the oral-facial-digital syndrome 1 gene (OFD1, formerly CXorf5) on chromosome arm Xp22.2
OFD I is associated with dysfunction of the primary cilia and is characterized by multiple abnormalities, including oral (cleft of the hard or soft palate; lobed tongue; hematomas or lipomas of the tongue; accessory gingival frenula; dental abnormalities), facial (median cleft or pseudocleft of the upper lip; micrognathia; ocular hypertelorism or telecanthus; hypoplasia of the alae nasi), digital (brachydactyly, syndactyly, clinodactyly, or polydactyly); brain (corpus callosum agenesis, intracerebral cysts, cerebellar agenesis with or without Dandy-Walker malformation); and kidney (polycystic kidney disease) abnormalities.3 Mild mental retardation is reported in as many as 50% of patients with OFD I.4
Diagnosis of OFD I usually is at birth and is based on typical clinical characteristics of the syndrome and genetic testing for the mutated OFD I gene.
Treatment of OFD I centers on repair of the abnormalities, removal of any accessory teeth, and orthodontia for any malocclusion.5 Treatment of seizures and/or renal disease, if present, also is required. Many patients will require speech therapy. Regular follow-up is recommended to screen for the development of renal disease, speech difficulties, or hearing abnormalities.
Salinas CF, Pai GS, Vera CL, et al. Variability of expression of the orofaciodigital syndrome type I in black females: six cases. Am J Med Genet. 1991;38(4):574-582.
Diz P, Álvarez-Iglesias V, Feijoo JF, et al. A novel mutation in the OFD1 (Cxorf5) gene may contribute to oral phenotype in patients with oral-facial-digital syndrome type 1. Oral Dis. 2011;17(6):610-614.
Oral-facial-digital syndrome. In: Jones K. Smith’s Recognizable Patterns of Human Malformation. 6th ed. Philadelphia, PA: Elsevier Saunders; 2006:292-295.
Toriello HV, Franco B. Oral-facial-digital syndrome type I. In: Pagon RA, Adam MP, Bird TD, et al, eds. GeneReviews. Seattle: University of Washington. http://www.ncbi.nlm.nih.gov/books/NBK1188/. Published July 24, 2002. Updated February 28, 2013. Accessed September 4, 2013.
Öztürk F, Doruk C. Orthodontic treatment of a patient with oral-facial-digital syndrome. Am J Orthod Dentofacial Orthop. 2012;141(4 suppl):S110-S118.