Double trisomy mosaicism is a rare phenomenon in live births. Cases reported in literature exhibited mainly combinations of both autosomal and sex chromosomes trisomies. Described chromosomes are mostly the same as found in single trisomies, i.e. reported combinations included often, in addition to XXX or XXY, autosomal trisomy 21,18 or less often trisomy 13 (1,5,7). Double trisomies involving the sex extra chromosome X are the most prevalent ones with various combinations of autosomal and gonosomal trisomies. Out of these, 48,XXX,+21; 48,XXX,+18 are the most common presentations in female cases (6). Clinically, it appeared that, in most cases, the extra chromosome X had not contributed to any phenotypic abnormalities, basing on the phenomenon of chromosome X-inactivation involving the extra X chromosome in triple X cell lines. (1,7,11).Trisomy 8 has been rarely described in double trisomy in liveboms, and the most reported cases are found among chromosomal aneuploidies, being cause of spontaneous abortions (4, 8). Characteristic features of mosaic Trisomy 8 syndrome (T8MS), also known as Warkany syndrome, include facial dysmorphism with long face, prominent forehead, hypertelorism with epicanthic folds, deep-set eyes, wide nasal bridge, large low-set, and dysplastic ears, thick lower lip and micrognathia, advanced growth, developmental delay, and common skeletal deformities. Dermatoglyphics are the most characteristic of the syndrome with deep longitudinal plantar furrows (9). Moderate intellectual deficiency had been typically described in T8 mosaicism individuals, but some reported cases had normal intelligence (9).We report here the first case of double trisomy mosaicism 48,XXX, +8/46,XX in a 7 years old Tunisian girl, who had clinically facial dysmorphism, growth and motor milestones delay, hypotonia and febrile seizures. We followed this patient during 5 years.Our patient, a female, was the first child born of healthy and unrelated Tunisian parents. At the time of birth her mother and father were 23 years old and 33 years old, respectively. Their second child was a healthy 1-year-old boy with apparently normal development. There was no family history of congenital abnormalities or mental retardation. The pregnancy was not regularly followed but there were no remarkable events or exposure to chemicals during pregnancy period. The patient was born at full term (40 weeks of gestation) by spontaneous vaginal delivery. She had 9 and 10 points in Apgar scale at 1 and 5 minutes of life, respectively. Birth measurements were as following: weight was 2000 g, length 38 cm and head circumference 29 cm, being all under the 3rd percentile. She was hospitalized at birth for hypotrophy but no malformations or facial dysmorphism were noted. Her two first years were marked by hypotonia, growth failure, and psychomotor delay: she laughed at six months, sat at twelve months, stood up at eighteen months, and walked alone at the age of 2 years and 1/2. She was hospitalized several times because of repetitive respiratory tract infections with or without hyperthermic seizures. An electroencephalogram was performed three times but no abnormalities were found in the intercritical periods.She was referred to our department at the age of 2 years. During her first physical exam, growth parameters were as following: weight 8 kg (At the first examination, chromosomal analysis of our propositusu0027 lymphocytes showed a mosaic karyotype with two cell lines: a double trisomie cell line and a normal cell line (48,XXX,+8 [25]/46,XX [25]) (Fig. …

Oculo-dento-digital dysplasia (ODDD) is a rare autosomal dominant disease characterized by a pleiotropic phenotype that primarily affects the eye, face, dentition and limb development with high level of penetrance and phenotypic variability ( 10). Diagnostic criteria of this disorder are facial anomalies involving ocular alterations with hypotelorism, microphtalmia and microcomea, pinched nose with hypoplastic nares and prominent columella, enamel hypoplasia and syndactyly type III, defined by bony and/or cutaneous fusion of fourth and fifth fingers and toes. Less frequent malformations including neurologic, hair and skin abnormalities can be observed as well (11,12). Neurologic manifestations in the ODDD are variable and include dysarthria, neurogenic bladder, bowel disturbances, spastic paraparesis, anterior tibial muscle weakness, and ataxia. They are classically exceptional during infancy and have a progressive onset by the second decade of life (9). In addition, intrafamilial variability of these neurologic signs has been reported in some familial ODDD cases with clinical anticipation through successive generations (2,11).ODDD is caused by mutations in GJA1 gene (Gap Junction Alpha 1) localized in 6q22.3. GJA1 involves two exons with encoding sequence starting at the exon 2. While, GJA1 has also one pseudogene GJAIP localized on 5q23, which has 97% sequence homology with GJA1 (11). This gene encodes the GJA1 protein, also named connexin 43 (Cx43), which belongs to the connexin proteins family. GJA1 is known to be the most ubiquitinously expressed connexin. All the connexin isoforms share the same architecture involving nine domains, among which six are relatively conserved, including four transmembrane and two extracellular loop domains, whereas, the three remaining domains, involving the intracytoplasmic loop domain and the amino and carboxyl termini are largely variable between connexins, and thus, are very likely responsible for specific function of each connexin isoforrn. The principal role of the connexin proteins is to constitute the gap junction channels, which are critical to electrical and metabolic intercellular exchanges, being at the base of physiologic equilibrium within different tissues and across different stages of life (13).In this study, we report the clinical and molecular findings in a three-generation Tunisian family with ODDD associated with neurologic manifestations.Table I summarizes clinical findings of the five affected individuals of this family.The proband was a female firstly referred to the department of congenital and hereditary diseases of the Charles Nicolle Hospital in Tunis for bilateral syndactyly of fingers and facial dysmorphism, seen at birth. Her family history revealed four other affected individuals having the same phenotypic anomalies. Three of them were examined and followed in our department. The pedigree of this non consanguineous Tunisian family is presented in Figure 1 (Fig. 1A).The proband (III1) was the first child of non-consanguineous parents. She was born at lull term after a normal pregnancy. Her Apgar scores were 9,10 at 1 and 5 minutes. Physical exam at birth was normal except for bilateral fingers syndactyly and facial dysmorphism. She was referred to our department at the age of one month. At that moment, all her measurements were at the 50th centile.Clinical examination showed bilateral complete syndactyly of the 4-5 fingers with camptodactyly and facial abnormalities including deep set eyes, microcomea, hypoplastic and anteverted nares with prominent columella and retrognathism. The rest of the physical exam was otherwise normal. Blood lymphocyte karyotype was normal. Radiographs of the hands revealed bilateral syndactyly of 4-5 fingers, with complete bone fusion of distal phalanges of the fourth and fifth rays. Physical examination of the proband's mother (112), maternal aunt (112), and maternal uncle (117) revealed the same facial characteristics, dental anomalies, bilateral 4-5 fingers syndactyly, and neurologic manifestations. …