Deafblindness is part of several genetic disorders. We investigated a consanguineous Egyptian family with two siblings affected by congenital hearing loss and retinal degeneration, initially diagnosed as Usher syndrome type 1. At teenage, severe enamel dysplasia, developmental delay, and microcephaly became apparent. Genome-wide homozygosity mapping and whole-exome sequencing detected a homozygous missense mutation, c.1238G>T (p.Gly413Val), affecting a highly conserved residue of peroxisomal biogenesis factor 6, PEX6. Biochemical profiling of the siblings revealed abnormal and borderline plasma phytanic acid concentration, and cerebral imaging revealed white matter disease in both. We show that Pex6 localizes to the apical extensions of secretory ameloblasts and differentiated odontoblasts at early stages of dentin synthesis in mice, and to cilia of retinal photoreceptor cells. We propose PEX6, and possibly other peroxisomal genes, as candidate for the rare cooccurrence of deafblindness and enamel dysplasia. Our study for the first time links peroxisome biogenesis disorders to retinal ciliopathies.

The 3-M syndrome is a rare autosomal recessive disorder. It is characterized by prenatal and postnatal growth retardation associated with characteristic features. In this study, we report on three patients from two unrelated families, including two male sibs, with the characteristic features and radiological findings of the 3-M syndrome. The main features in our cases were low birth weight, short stature, malar hypoplasia, anteverted nostrils with a fleshy nasal tip, long philtrum, pointed full chin, short broad neck, broad chest with transverse grooves of anterior thorax and hyperlordosis. An orodental examination revealed characteristic findings, some of which were not reported before. Prominent premaxilla, hypoplastic maxilla, thick patulous lips, high-arched palate, median fissured tongue, delayed eruption of teeth with enamel hypocalcification and malocclusion were present in our three studied cases. Radiographic studies showed slender long bones and ribs, a narrow pelvis and foreshortened vertebral bodies. Our reported cases are the offspring of healthy consanguineous parents, confirming the autosomal recessive pattern of inheritance in the syndrome. Cases were reported from different countries all over the world. To our knowledge, these are the first reported Egyptian patients with this rare disorder. This syndrome may be underreported because of the phenotypic overlap with other low birth dwarfism syndromes. Recent identification of a gene mutated in some cases of 3-M syndrome will aid diagnosis.

Ligneous conjunctivitis (MIM 217090) is a rare autosomal recessive hereditary disorder. We report a case with both ligneous conjunctivitis and ligneous periodontitis in association with plasminogen type I deficiency. Diagnosis was based on the clinical and histological findings and most importantly, decreased serum level of plasminogen type I.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.

Mucous membrane pemphigoid should be considered in the differential diagnosis of chronic desquamative gingivitis in childhood. Occlusive therapy with topical fluocinonide may alleviate the symptoms.