Autosomal recessive acro‐fronto‐facio‐nasal dysostosis associated with genitourinary anomalies

We report on two brothers, born to double first cousin Jordanian Arab parents, with a syndrome comprising severe hypertelorism with upslanted palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Both have severe myopia, mild to moderate sensori-neural hearing loss and borderline intelligence. Results of chromosome analysis were normal as was a FISH assay for subtelomeric rearrangements. The father has mild hypertelorism but the family history is otherwise unremarkable. We think that this represents a previously unrecognized autosomal or X-linked recessive syndrome.

Section: Discussionmentioning

confidence: 97%

Severe hypertelorism, midface prominence, prominent/simple ears, severe myopia, borderline intelligence, and bone fragility in two brothers: New syndrome?†

Hamamy¹,

Teebi

Oudjhane

et al. 2007

“…Differential diagnosis includes AFFND, which in original description included two types, probably the spectral variations of a single condition. Type I (OMIM 201180) consisted of short stature, hypertelorism, broad and bifid nasal tip, cleft lip and/or palate, postaxial camptobrachypolysyndactyly, other skeletal anomalies and ID (Richieri‐Costa et al, ), whereas the later described type II (OMIM 239710) consisted of facial midline defects, polysyndactyly, and genitourinary anomalies, but not ID (Richieri‐Costa, Montagnoli, & Kamiya, ). Only a few patients with AFFND have been reported after the first description (Balci et al, ; Chaabouni et al, ; Guion‐Almeida & Richieri‐Costa, ; Naguib, ; Prontera et al, ; Teebi, ).…”

Section: Discussionmentioning

confidence: 99%

Homozygous indel mutation in CDH11 as the probable cause of Elsahy–Waters syndrome

Taşkıran

Karaosmanoğlu

Koşukçu

et al. 2017

Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Other findings included bilateral partial cutaneous syndactyly of 2nd and 3rd fingers, history of impacted teeth with dentigerous cyst in the elder one, and intellectual disability (mild and borderline). The sisters were considered to have Elsahy-Waters syndrome. In order to elucidate the underlying molecular cause, sisters and their healthy parents were genotyped by SNP arrays, followed by homozygosity mapping. Homozygous regions were further analyzed by exome sequencing in one affected individual. A homozygous indel variant segregating with the condition was detected in CDH11 (c.1116_1117delinsGATCATCAG, p.(Ile372MetfsTer9)), which was then validated by using Sanger sequencing. CDH11 encodes cadherin 11 (osteo-cadherin) that regulates cell-cell adhesion, cell polarization and migration, as well as osteogenic differentiation. Further experiments revealed that CDH11 expression was decreased in patient-derived fibroblasts as compared to the heterozygous parent and another healthy donor. Immunostaining showed absence of the protein expression in patient fibroblasts. In addition, cell proliferation rate was slow and osteogenic differentiation potential was delayed. We consider that this study reveals loss-of-function mutations in CDH11 as a probable cause of this phenotype. Next generation sequencing in further patients would both prove this gene as causative, and finely delineate this clinical spectrum further contributing in identification of other possibly involved gene(s).

“…In the three reports, patients are born of consanguineous parents, with familial recurrence in some cases [Naguib, 1988;Richieri-Costa et al, 1989]. We suggest an autosomal recessive inheritance for this condition based on parental consanguinity and multiple affected male and female siblings.…”

Section: Discussionmentioning

confidence: 86%

“…AFFND type II (OMIM 239710) includes facial midline defects, polysyndactyly and genitourinary anomalies. The second type of AFFND is not associated with mental retardation [Richieri-Costa et al, 1989]. Naguib [1988] also described a presumably autosomal recessive new hypertelorism-hypospadiaspolysyndactyly syndrome in three males and a female sibling.…”

Section: Introductionmentioning

confidence: 94%

Autosomal recessive acro‐fronto‐facio‐nasal dysostosis associated with genitourinary anomalies: A third case report

Chaâbouni

Mâazoul

Hamida

et al. 2008

We report on a 22-day-old Tunisian boy born to consanguineous (first-cousin) parents (F = 1/16). The patient presents wide forehead with frontal encephalocele, wide anterior fontanel, marked hypertelorism, coloboma of the upper lids, proptosis, congenital glaucoma, broad nose, syndactyly between fingers 3 and 4, hypoplastic 3rd, 4th and 5th toes with nail dysplasia, hypospadias with cleft glans, bifid scrotum. Brain MRI showed right frontal encephalocele with anomalies of the cortical gyration without any corpus callosum abnormality. Normal chromosomes and parents' consanguinity are suggestive of autosomal recessive inheritance. Facial midline anomalies associated with limb and genitourinary anomalies is very uncommon. We present the third case reported in the literature.