Sonic Hedgehog deletion and distal trisomy 3p in a patient with microphthalmia and microcephaly, lacking cerebral anomalies typical of holoprosencephaly

Case Report 3p partial trisomy and 13q partial monosomy with congenital malformations and psychomotor developmental delay

“…Most of the clinical manifestations described in our patient are known to occur in both trisomy 3p and monosomy 13q syndromes, individually. Other phenotype manifestations are compatible with the clinical alterations related to 3p trisomy patients (Reiss et al, 1986;Chen et al, 2008;Ginocchio et al, 2008;Tan et al, 2011;Han et al, 2012), and some are related to 13q monosomy (Schinzel, 1983;Brewer et al, 1998;Brooks et al, 2006;Ballarati et al, 2007;Quélin et al, 2009), as shown in Tables 1 and 2. The partial 13q monosomy commonly produces malformations such as microcephaly, ear abnormalities, retrognathia, hypertelorism, palate fissures, hypotonia, and skeletal abnormalities, as well as psychomotor development delay and heart defects ( Table 1). The partial 3p trisomy has been known as a syndrome with multiple congenital abnormalities and intellectual deficiency, characterized by micrognathia, short neck, hypertelorism, large mouth with downturned angles, prominent philtrum, speech delay, congenital heart disease, and neuropsychomotor retardation.…”

“…Moderate mental retardation, hypotonia, hypertelorism, foot anomalies, skeletal abnormalities (Ballarati et al, 2007) Dysmorphic facial features, hypertelorism, cleft lip and palate, large low-set ears, short neck, single transverse palmar creases in both hands, hypochromic gray irides and pin point pupils, dysgenesis of the corpus callosum (Han et al, 2012) 3p23 Death during the first 2 years of life, psychomotor retardation, braquicephaly, square-shaped face, hypertelorism, micrognathia, short neck, congenital heart disease, frontal bossing, palate fissure, temporal depression, fingertip whorls (Reiss et al, 1986) 3p24.2 Cleft palate and hypotonia with gross motor and fine motor delay, speech delay, moderate atrial septal defect, recurrent otitis media (Tan et al, 2011) 3p25 After-birth death, psychomotor retardation, frontal bossing, square-shaped face, hypertelorism, micrognathia, congenital heart disease, temporal depression (Reiss et al, 1986) 3p26.3 Microcephaly, bilateral microphthalmia, retinochoroidal coloboma, malformed and posteriorly rotated ears, retrognathia, speech delay, "cupid's bow" superior lip, single palmar crease, flat feet, nail fragility, optic nerve hypoplasia, delayed bone age (Ginocchio et al, 2008) Finally, it should not be neglected that the father has a balanced translocation involving chromosomes 3 and 13, and even though he does not manifest any phenotypic abnormality, he has a higher probability of reproductive problems including miscarriages and descendants with chromosome abnormalities. The risk to carriers of balanced translocations has been shown to vary according to the chromosomal segments involved in the structural rearrangement.…”

Cryptic 7q36.2q36.3 deletion causes multiple congenital eye anomalies and craniofacial dysmorphism

“…The report of overlapping deletions in other patients supports the pathogenic role of submicroscopic chromosomal rearrangements involving 7q36 [Frints et al, 1998;Horn et al, 2004;Ginocchio et al, 2008]. Our patient's presentation appears partially congruent with that of another patient with a partially overlapping deletion; particularly ocular anomalies associated with SHH loss-of-function mutations and holoprosencephaly [Pineda-Alvarez et al, 2011].…”

“…In silico analysis indicates that the last four genes listed are involved in development. Larger 7q36.3-qter deletions have been described in the literature [Frints et al, 1998;Horn et al, 2004;Ginocchio et al, 2008]. Most of these patients presented significant psychomotor development delay, failure to thrive, microcephaly, holoprosencephaly spectrum disorders and associated brain malformations.…”

7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly Case

“…Although the most severe forms of HPE cases involve 7q deletion and 3p duplication [Chen et al, 1999], others are accompanied by 2q, 2p, 8p, 18q, 1q, and 22q duplication [reviewed in Ayub et al, 2016]. There are at least 3 exceptional cases of patients without HPE, despite being carriers of a 7q deletion and other chromosome duplications [Kuller et al, 1992;Ginocchio et al, 2008;Ayub et al, 2016]. This could be explained by the fact that none of the genes involved in brain development are present in the duplicated region.…”