MedGen

Any holoprosencephaly in which the cause of the disease is a mutation in the SHH gene. [from MONDO]

A rare disorder characterized by the partial separation of the cerebral hemispheres. It is associated with mutations in the SIX3 gene. [from NCI]

Holoprosencephaly (HPE) is the most commonly occurring congenital structural forebrain anomaly in humans. HPE is associated with mental retardation and craniofacial malformations. Considerable heterogeneity in the genetic causes of HPE has been demonstrated (Ming et al., 2002). For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). [from OMIM]

X-linked Opitz G/BBB syndrome (X-OS) is a multiple-congenital-anomaly disorder characterized by facial anomalies (hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum), and laryngotracheoesophageal defects. Developmental delay and intellectual disability are observed in about 50% of affected males. Cleft lip and/or palate are present in approximately 50% of affected individuals. Other malformations (present in <50% of individuals) include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female heterozygotes usually manifest hypertelorism only. [from GeneReviews]

Weyers acrofacial dysostosis (WAD) is an autosomal dominant disorder with dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. Ellis-van Creveld syndrome is a similar disorder, with autosomal recessive inheritance and the additional features of disproportionate dwarfism, thoracic dysplasia, and congenital heart disease (summary by Howard et al., 1997). [from OMIM]

Holoprosencephaly-9 refers to a disorder characterized by a wide phenotypic spectrum of brain developmental defects, with or without overt forebrain cleavage abnormalities. It usually includes midline craniofacial anomalies involving the first branchial arch and/or orbits, pituitary hypoplasia with panhypopituitarism, and postaxial polydactyly. The disorder shows incomplete penetrance and variable expressivity (summary by Roessler et al., 2003 and Bertolacini et al., 2012). For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). [from OMIM]

A single maxillary central incisor positioned in the midline with morphological symmetry of the crown and bordered by lateral incisors. [from HPO]

Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head."

MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.

Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.

People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems. [from MedlinePlus Genetics]

Developmental and epileptic encephalopathy-85 with or without midline brain defects (DEE85) is an X-linked neurologic disorder characterized by onset of severe refractory seizures in the first year of life, global developmental delay with impaired intellectual development and poor or absent speech, and dysmorphic facial features. The seizures tend to show a cyclic pattern with clustering. Many patients have midline brain defects on brain imaging, including thin corpus callosum and/or variable forms of holoprosencephaly (HPE). The severity and clinical manifestations are variable. Almost all reported patients are females with de novo mutations predicted to result in a loss of function (LOF). However, some patients may show skewed X inactivation, and the pathogenic mechanism may be due to a dominant-negative effect. The SMC1A protein is part of the multiprotein cohesin complex involved in chromatid cohesion during DNA replication and transcriptional regulation; DEE85 can thus be classified as a 'cohesinopathy' (summary by Symonds et al., 2017 and Kruszka et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. [from OMIM]

Distal chromosome 19q13.11 deletion syndrome is an autosomal dominant neurodevelopmental disorder characterized by poor overall growth, slender habitus, microcephaly, delayed development, intellectual disability with poor or absent speech, and feeding difficulties. Additional features include dysmorphic facies, signs of ectodermal dysplasia, hand and foot anomalies, and genitourinary anomalies, particularly in males (summary by Chowdhury et al., 2014). [from OMIM]

X-linked holoprosencephaly-13 (HPE13) is a neurologic disorder characterized by midline developmental defects that mainly affect the brain and craniofacial structure. The severity and manifestations are variable: some patients may have full alobar HPE with cyclopia, whereas others have semilobar HPE or septooptic dysplasia. Dysmorphic features include microcephaly, hypotelorism, low-set ears, micrognathia, and cleft lip/palate. Patients with a more severe phenotype may die in the newborn period, whereas those with a less severe phenotype show global developmental delay. Additional variable features include congenital heart defects and vertebral anomalies. Phenotypic variability may be related to the type of mutation, X-inactivation status, and possible incomplete penetrance. The STAG2 protein is part of the multiprotein cohesin complex involved in chromatid cohesion during DNA replication and transcriptional regulation; HPE13 can thus be classified as a 'cohesinopathy' (summary by Kruszka et al., 2019). For a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). [from OMIM]

A multisystem malformation syndrome that has been reported in about 10 patients. The clinical features include bilateral anophthalmia, abnormal nares, central nervous system anomalies, and neurodevelopmental delay. Additional features include brachycephaly and other facial anomalies. Non-facial anomalies have also been reported: postaxial polydactyly, genital hypoplasia. All cases reported so far have been sporadic, suggesting that the syndrome may be due to a new dominant mutation. [from SNOMEDCT_US]

Multiple types of congenital heart defects-8 (CHTD8) is characterized by cardiac septal defects, double-outlet right ventricle, unbalanced complete atrioventricular canal, and valvular anomalies, as well as vascular anomalies including dextroposition of the great arteries, anomalous pulmonary venous return, and superior vena cava to left atrium defect. Patients may also exhibit laterality defects, including dextrocardia, atrial isomerism, dextrogastria, left-sided gallbladder, and intestinal malrotation (Zaidi et al., 2013; Granadillo et al., 2018). [from OMIM]

A rare genetic congenital limb malformation syndrome with characteristics of short stature, sparse scalp hair, hypoplastic, proximally placed thumbs and skin hyperpigmentation with areas of ''raindrop'' depigmentation. Presence of a single, upper central incisor has also been reported. There have been no further descriptions in the literature since 1988. [from SNOMEDCT_US]