Philippines

Synonyms: Orofacial clefts, cheilognathopalatoschisis ¹
 
Definition: Bilateral cleft lip with or without cleft palate is a  defect in the upper lip and alveolar ridge caused by failure of normal migration or fusion of the maxillary processes and the medial nasal process ².

Case report: This is the ultrasound scan done on a 27 year old G1,P0 who presented for the first time at 28 weeks of gestation. She had no significant medical history.

The image demonstrates bilateral hypoechoic defects in the upper lip just beneath both the nares. Sagittal  view of the fetal face showed premaxillary protrusion. Transverse axial views were not available. No other anomalies were detected.

Prevalence: Orofacial clefts are common in Asians with a prevalence of 15-20:10,000 births. Prevalence in whites is 10:10,000 births and 3:/0,1000 for blacks ³. 
 
Etiology: The cause is multifactorial. In 36 Filipino families with 3 or more affected members, chromosomes 6p23, 2p13, 1p36 were implicated ⁴. Several orofacial cleft (OFC) gene loci have been mapped to chromosomes 6p24 (OFC1), 2p13 (OFC2), 19q3 (OFC3)  and 4q (OFC4). Aside from genetic factors, environmental factors like maternal smoking may increase the risk for isolated cleft lip and palate especially  for infants with transforming growth factor alpha allele ⁵.

Sonographic findings: Coronal view of the fetal face shows bilateral hypoechoic defects in the upper lip just beneath both nares. Sagittal view of the fetal face shows premaxillary protrusion positioned anterior and inferior to the fetal nose. Transverse axial plane shows disruption in the normally smooth C shaped contour of the alveolar ridge ⁶.

Standardized 3- D multiplanar images allow a systematic evaluation of lip defects and abnormalities of the maxillary tooth-bearing alveolar ridge. The accuracy of adjunctive 3D ultrasound is superior to 2D ultrasound alone for extensive prenatal diagnosis of cleft lip with or without cleft primary palate ⁷. 

Doppler ultrasound may aid in prenatal diagnosis by demonstrating abnormal flow from the buccal cavity into the nasal fossa. This would aid in demonstrating small defects in the palate that may be missed with conventional 2-D ultrasound ⁸.

Associated anomalies: An abnormal karyotype with their attendant anatomic abnormalities is associated with 15% of fetuses with bilateral cleft lip and palate. Trisomy 13 fetuses display the most pronounced defects, predominantly median clefts. Fetuses with Trisomy 18 present with larger clefts compared with fetuses with normal karyotype ⁹.   
For fetuses with normal chromosomes, the risk of an associated anatomic abnormality increases with the severity of the cleft . Twenty percent  of fetuses with bilateral cleft lip/palate will have  other anatomic abnormalities compared with only 5% for those with unilateral cleft lip ¹⁰. The most common anatomic abnormalities associated with orofacial clefts are congenital heart (eg  ASD)  and central nervous system defects. Other anomalies that may be detected are limb, gastrointestinal tract and renal abnormalities. 

Recurrence risk: The risk of recurrence depends on the number of affected relatives. The risk is  4% with one affected parent; 4% with  one sibling; 9% if with  2 affected siblings and 17% if one sibling and 1 parent are affected; 60 % if two parents plus one affected sibling ¹¹.

Management: Management would depend on the severity of the cleft and  the presence of other significant anomalies. For isolated  cleft lip with or without cleft palate, various surgical techniques have been devised for correcting the deformity postnatally.

References:
1. Bull, HG, Lenzen C.: Differential Diagnosis and Treatment of Cheilognathopalatoschisis. Zetralbl Gynakol. 2003 Oct.; 125  (10): 398-403
2. Melnick M.: Cleft lip and palate: Etiology and Pathogenesis. Kenahan PA, Rosenstein SW, Dado DV (eds): Cleft lip and palate: A system of management, Baltimore MD, Williams and Wilkins, 1990 p. 2.
3. Gorlin RJ, Cohen MM Jr., Levin CS: Orofacial clefting syndromes: General Aspects. In Gorlin RJ, Dohen MM Je. Levin LS (ed): Syndrome of the Head and Neck 3rd ed. New York, Oxford Universitiy Press, 1990 0. 693
4. Schultz, R.E.; Cooper ME; Daack-Hirsch, S; Shi, M; Nepomucena, B; Graf, K.A.; O'Brien ,EK; O'Brien , SE; Marazita, ML; Murray JC: Targeted scan of fifteen regions for nonsyndromic cleft lip and palate in Filipino families. Am. J. Med. Genet. 125A:17-22, 2004.
5. Shaw G.M.; Wasserman, C.R.; Lammer, E.J.; O'Malley. C.D. Murrey, J.C.; Basart, A.M.;Tolarova, M.M.: Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants. Am. J. Hum. Genet. 58: 551-561, 1996. PubMed ID: 8644715
6. Callen
7. Mittermayer C., Blaicher W., Brugger P.C. Beraschek G., Lee A.: Foetal facial clefts: prenatal evaluation of lip and primary palate by 2D and 3D ultrasound. Ultraschall Med. 2004 Apr; 25 (2):120-5.
8. Aubry MD,  Aubry JP: Prenatal diagnosis of cleft palate: contribution  of color Doppler ultrasound. Ultrasound Obstet Gynecol. 1992 May 1;2(3):221-4.
9. Berge SJ, Plath H, Reich RH, Hansmann M: Significance of prenatal diagnosis of lip-jaw-palatal clefts. Mund Kiefer Gesichtschir 2002 Mar 6 (2) 85-90.
Berge SJ
10. Babcock, CJ: The Fetal Face and Neck: Facial Clefts. In  Callen, PW (ed): Ultrasonography in Obstetrics and Gynecology 4th ed.  WB Saunders Company , 2000 p.  324.
11. Jurkiewicz MJ, Krizek TJ, mathes SJ, Ariyan S (eds): Plastic Surgery: Principles and Practice. St. Louis, MO, CV Mosby, 1990.