• a unit of heredity
• functional unit of strands of DNA
• tens of thousands of genes in the human genome pool

• a linear double strand of DNA
• each chromosome contains thousands of genes
• humans have 46 (23 pairs) of chromosomes
• chromosomes contain the complete set of instructions for cell replication & differentiation
• chromosomes 1-22 have 2 copies - one from each parent - called autosomes
• last set called the sex chromosomes - again one from each parent - may be either X (female) or Y(male)

• change in the # of copies
• monosomy - only 1 chromosome instead of 2 in the set
• trisomy - extra copy of the chromosome in the set
• survival is rare in situations of monosomy, but possible with trisomy
• most common trisomy condition is trisomy 21 which results in Down's syndrome
• deletions
• part of a chromosome is separated or lost
• results in multiple malformations & developmental handicaps in child
• duplications
• duplicates of parts of the chromosome occur
• inversions
• portion of chromosome are rotated 180 degrees
• translocations
• transfer of genetic material between 2 or more chromosomes

Genetic disorders

• all individuals carry genes with mutations capable of causing disease
• however, since you have 2 copies of each gene one complete copy is usually sufficient
• traits governed by identified genes are said to be either recessive or dominant
• recessive traits become expressed only if both genes have same mutations (homozygous)
• dominant traits will be apparent even if only 1 gene in the pair has the mutation (heterozygous)

• autosomal recessive inheritance
• gene is found on one of the autosomes (chromosomes 1-22)
• requires both copies of gene to be affected with the mutation for expression of the trait/abnormality
• carriers have one abnormal copy of a gene but no detectable abnormalities
• carriers are said to be heterozygous i.e. have 2 different copies of a particular gene
• common autosomal recessive diseases include (1) cystic fibrosis (2) sickle cell anemia (3) Tay-Sachs
• autosomal dominant inheritance
• trait is apparent when only 1 gene is affected with the mutation/abnormality
• above would be case of heterozygous individual
• expression of the trait/abnormality is more severe in those that have 2 affected genes (homozygous)
• X-linked inheritance
• mutant genes occur on the X chromosome
• many X-linked recessive conditions - only a few X-linked dominant conditions
• females often have no effects or milder effects if the mutation is a recessive X-linked gene (have 1 healthy gene on the other X chromosome)
• males do not have another X chromosome so do not have another gene
• therefore X-linked recessive disorders affect males almost exclusively
• X-linked dominant disorders are rare & usually lethal to males
• multifactorial inheritance
• result of interaction of multiple genes with environmental influences
• teratogens - environmental factors known to increase risks of birth defects
• cleft lip with or without cleft palate, cleft palate alone and VPI are all examples of multifactorial inheritance
• common teratogens for birth defects include ethanol, cigarette smoke, seizure medications, congenital infections

• result from either malformation, dysplasia, deformation
• morphogenesis - process of embryonic tissue formation
• dysmorphogenesis - errors in the process of tissue formation
• dysmorphic features - features that are abnormally formed
• causes may be external(nongenetic) or intrinsic (genetic, developmental abnormalities)
• malformation
• result of abnormal developmental process that has genetic etiology
• cleft lip & many cases of cleft palate may be the result of a malformation
• dysplasia
• abnormal organization of cells into tissues
• also related to genetic factors
• example is craniosynotoses - premature fusion of 1 or more cranial sutures
• deformation (deformity)
• physical forces in fetal environment cause abnormal shape of a completely formed organ or structure
• usually from external agent - teratogen
• cleft palate could be caused by non-genetic forces & be considered a deformation

• syndromes - pattern of multiple anomalies that have a common known or suspected cause
• sequence - pattern of multiple anomalies that arise from a single known prior anomaly i.e. the first anomaly causes others to occur
• association - pattern of multiple anomalies in 2 or more individuals where the pathogenesis is not known, genetic etiology can't be determined also no developmental or teratogenic cause

• cleft occurs in the primary palate (lip, median alveolar ridge, premaxilla)
• common birth defect with racial differences in incidence
• 1 in 800 Caucasian
• 1 in 2000 African  & African American
• 1 in 500  Asian
• 1 in 300  Native American
• boys affected more than girls
• left-side more common than right
• most cases are isolated with no associated syndromes or other birth defects
• there is a substantial genetic link in many families
• over 180 syndromes do have cleft lip as part of the syndrome

• cleft occurs in the secondary palate (hard palate & velum)
• cleft of palate without co-occurring cleft lip occurs in 1 in 2000 live births
• more likely to be associated with syndrome or other congenital anomaly than Cleft lip
• 376 syndromes, excluding the chromosome disorders have cleft palate as part of the syndrome
• may be considered a malformation but may also be due to disruption of normal development (deformation) - hard to distinguish