Blepharophimosis‐mental retardation (BMR) syndromes: A proposed clinical classification of the so‐called Ohdo syndrome, and delineation of two new BMR syndromes, one X‐linked and one autosomal recessive

Abstract

We report on 11 patients from 8 families with a blepharophimosis and mental retardation syndrome (BMRS) phenotype. Using current nosology, five sporadic patients have Ohdo syndrome, associated with congenital hypothyroidism in two of them (thus also compatible with a diagnosis of Young-Simpson syndrome). In two affected sibs with milder phenotype, compensated hypothyroidism was demonstrated. In another family, an affected boy was born to the unaffected sister of a previously reported patient. Finally, in the last sibship, two affected boys in addition had severe microcephaly and neurological anomalies. A definitive clinical and etiologic classification of BMRS is lacking, but closer phenotypic analysis should lead to a more useful appraisal of the BMRS phenotype. We suggest discontinuing the systematic use of the term "Ohdo syndrome" when referring to patients with BMRS. We propose a classification of BMRS into five groups: (1) del(3p) syndrome, (possibly overlooked in older reports); (2) BMRS, Ohdo type, limited to the original patients of Ohdo; (3) BMRS SBBYS (Say-Barber/Biesecker/Young-Simpson) type, with distinctive dysmorphic features and inconstant anomalies including heart defect, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism. BMRS type SBBYS is probably an etiologically heterogeneous phenotype, as AD and apparently AR forms exist; (4) BMRS, MKB (Maat-Kievit-Brunner) type, with coarse, triangular face, which is probably sex-linked; (5) BMRS V (Verloes) type, a probable new type with severe microcephaly, hypsarrhythmia, adducted thumbs, cleft palate, and abnormal genitalia, which is likely autosomal recessive. Types MKB and V are newly described here.

Young–Simpson syndrome (YSS), a variant of del(1)(p36) syndrome?

“…Since 1987, nine more YSS patients have been published [Fryns and Moerman, 1988;Cavalcanti, 1989;Bonthron et al, 1993;Nakamura and Noma, 1997;Masuno et al, 1999;Kondoh et al, 2000;Verloes et al, 2006]. The manifestations in these patients are very similar to those seen in patients with a terminal deletion of the short arm of chromosome 1.…”

“…This observation may partially explain why patients with 1p36 deletions have not been reported to have epicanthus inversus. Verloes et al [2006] suggested that YSS is probably genetically heterogeneous. We suggest, based on genetic testing along with clinical observation that YSS is due to a deletion in the terminal region on the short arm of chromosome 1.…”

“…Specifically, the congenital heart defects detected were a moderate ventricular septal defect with a large secundum type ASD [Young and Simpson, 1987], an atrioventricular canal [Bonthron et al, 1993], a patent ductus arteriosus [Nakamura and Noma, 1997], a perimembranous VSD with ostium secundum defect ASD [Masuno et al, 1999] and an ASD, ostium secundum type, perimembranous VSD, right-sided aortic arch, and a PDA that persisted beyond the neonatal period [Verloes et al, 2006]. Thus, our case is the first case of YSS associated with dilated cardiomyopathy, which is commonly seen in 1p36 monosomy patients.…”

Two-Step Surgery for Telecanthus-Epicanthus and Ptosis in Patients with Blepharophimosis

“…Bu hastalarda flafl›-l›k ve ambliyopi s›kl›¤› normal nüfusa k›yasla daha yüksek saptanm›flt›r (2). Genifl ve düz burun kökü, damak ve kulak anomalileri, sporadik olarak mental retardasyon, gonadal anomaliler rastlanan göz d›fl› bulgulard›r (4)(5)(6).…”

Blepharophimosis mental retardation syndrome Say‐Barber/Biesecker/Young‐Simpson type – New findings with neuroimaging

“…[Ohdo et al, 1986]. In 2006, a new classification of BMRS delineating five groups was introduced in which the use of the term ''Ohdo syndrome'' was suggested to remain restricted to the original patients of Ohdo [Verloes et al, 2006]. Patients sharing a characteristic facial phenotype and a combination of additional anomalies including heart defects, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism are referred to as having BMRS SBBYS type [Verloes et al, 2006].…”