Genetics of cleft lip and cleft palate in China.

During the past 10 years, 60 cases of cleft lip with or without cleft palate [CL(P)] were recorded among 45,072 newborns at Shanghai International Peace Maternity and Infant Hospital, China. The incidence was 1.33 per 1,000 births. The family histories of 163 CL(P) patients were analyzed. The incidences of CL(P) in the first-, second-, and third-degree relatives of CL(P) patients were 11/246 (4.47%), 10/1,032 (0.97%), and 6/1,727 (0.35%), respectively. Of the 163 probands, three had a history of consanguinity of the parents (1.8%), in contrast to 0.77% in the general population. These data are suggestive of multifactorial inheritance. The heritability of CL(P) in our study calculated by Falconer's formula was 77.6%.     

Distichiasis and cleft palate

A patient with the unusual coexistence of distichiasis and cleft palate is described. Distichiasis is a rare congenital eyelid anomaly in which accessory eyelashes are present in the meibomian gland orifices. Its association with other systemic abnormalities is reviewed; the distinctions among distichiasis, trichiasis, entropion, and epiblepharon are outlined; and methods of treatment for distichiasis are described.     

Mouse genetic models of cleft lip with or without cleft palate

Nonsyndromic cleft lip and palate (CLP) is among the most common human birth defects. Transmission patterns suggest that the causes are "multifactorial" combinations of genetic and nongenetic factors, mostly distinct from those causing cleft secondary palate (CP). The major etiological factors are largely unknown, and the embryological mechanisms are not well understood. In contrast to CP or neural tube defects (NTD), CLP is uncommon in mouse mutants. Fourteen known mutants or strains express CLP, often as part of a severe syndrome, whereas nonsyndromic CLP is found in two conditional mutants and in two multifactorial models based on a hypomorphic variant with an epigenetic factor. This pattern suggests that human nonsyndromic CLP is likely caused by regulatory and hypomorphic gene variants, and may also involve epigenetics. The developmental pathogenic mechanism varies among mutants and includes deficiencies of growth of the medial, lateral or maxillary facial prominences, defects in the fusion process itself, and shifted midline position of the medial prominences. Several CLP mutants also have NTD, suggesting potential genetic overlap of the traits in humans. The mutants may reflect two interacting sets of genetic signaling pathways: Bmp4, Bmpr1a, Sp8, and Wnt9b may be in one set, and Tcfap2a and Sox11 may be in another. Combining the results of chromosomal linkage studies of unidentified human CLP genes with insights from the mouse models, the following previously unexamined genes are identified as strong candidate genes for causative roles in human nonsyndromic CLP: BMP4, BMPR1B, TFAP2A, SOX4, WNT9B, WNT3, and SP8.     

Racial differences in cephalometric measurements and incidence of cleft lip with or without cleft palate

A study was made to search for the morphological basis and, indirectly, the developmental basis for racial differences in risk of cleft lip with or without cleft palate CL(P) in Hawaii. A total of ten linear and three angular measurements read from anterior-posterior cephalographs were examined on 210 healthy adult Caucasian, Hawaiian, Japanese, Chinese, and Filipino subjects. Racial comparisons were made on these variables after adjusting for age and sex. Generally, the CL(P) high-risk group consisting of Japanese, Chinese, and Filipinos had smaller dimensions than Caucasians and Hawaiians in the variables (S-N, N-Ba) representing size of cranial base and the measurements of face height (N-A, N-ANS), palatal length (ANS-PNS), and mandibular length (Ar-Gn). Facial width relative to palatal length as measured by the ratio of bizygomatic diameter to palatal length showed a marked consistency with the racial differences in CL(P) risk. Possible significance of this finding is discussed in relation to development of the orofacial structure.