New Ectodermal Dysplasia-Holoprosencephaly Syndrome Associated With 45,XY,der(15;18)(q10;q10)

Objective: we would like to report a 28-year-old Thai man with a unique combination of features. Methods: clinical, radiographic examinations, and cytogenetic analysis were performed. Results: the characteristic features consisted of microcephaly, mental retardation, neonatal hypothyroidism, partial expressive aphasia, and long fingers. The toenails and fingernails were thin, brittle and longitudinally grooved. Oral findings included single median maxillary central incisor, protruded premaxilla, absent maxillary labial frenum, highly arched and V-shaped palate, pronounced medial palatal ridge with deep furrows along the midline, and taurodontism of molars. Multiple carious teeth were noted. He was born with normal hair but kept losing hair since age 6 years. Examination at age 16 years, alopecia totalis was noted. His karyotype was 45,XY,der(15;18)(q10;q10) or 45,XY,der(15;18)(15qter->15q10::18q10->18qter). The combinations of features found in this patient appeared to be the combined effects of the missing of the genes on chromosome 18p. TGIF, the gene responsible for holoprosencephaly is mapped to 18p11.3. Linkage analysis of an autosomal dominant form of hereditary hypotrichosis simplex also maps to 18p11.32-p11.23. Conclusion: it is concluded that the unique combination of the features of ectodermal dysplasia and holoprosencephaly found in this patient was caused, at least in part, by haploinsufficiency of TGIF and the gene responsible for hereditary hypotrichosis simplex. This would suggest that this newly recognized ectodermal dysplasia-holoprosencephaly syndrome may be regarded as a contiguous gene syndrome caused by 18p11.3 deletion. This research was supported by The Thailand Research Fund (TRF).