A primigravid woman at 22 weeks gestation comes to the office with her partner to discuss a cleft lip and palate identified on prenatal ultrasound. The father requests a paternity test of the fetus because no one on his side of the family has ever had a cleft lip or palate. During your discussion with the family, you explain to them that children with cleft lip and palate often have no family history of the condition because it is most commonly due to which of the following?

Question

A primigravid woman at 22 weeks gestation comes to the office with her partner to discuss a cleft lip and palate identified on prenatal ultrasound.  The father requests a paternity test of the fetus because no one on his side of the family has ever had a cleft lip or palate.  During your discussion with the family, you explain to them that children with cleft lip and palate often have no family history of the condition because it is most commonly due to which of the following?

Quizplus · Accepted Answer

11ec160b_3757_e111_9249_cde10a11e040_MD0001_00 This patient has a prenatally identified cleft lip and palate with no known family history of the condition. Most cases are multifactorial and related to a combination of multiple interacting genetic and environmental factors. Cleft lip results when the maxillary prominence fails to fuse with the intermaxillary segment during the fifth or sixth week of embryonic development. Cleft palate occurs when the palatine shelves fail to fuse with each other or with the primary palate. Cleft lip and palate can occur together or in isolation. Because of the complexity of embryologic development, many genetic abnormalities (eg, genes controlling cell differentiation, communication, and migration) can lead to failure of this fusion. Environmental risk factors have also been identified (eg, antiepileptic drugs, maternal smoking, folate deficiency) that increase the risk of cleft lip and palate in genetically susceptible individuals. Genetic syndromes (with multiple inheritance patterns) are responsible for approximately 30%-50% of cleft palate cases (eg, 22q11 deletion syndrome). (Choice A) Autosomal recessive inheritance can be responsible for some forms of syndromic cleft lip and palate, which can lead to index cases with no family history. However, most cases are caused by multifactorial inheritance, particularly in the absence of other findings consistent with a genetic syndrome. (Choice B) An embryologic disruption refers to an interruption of normal organ development due to an outside influence. For instance, amniotic bands can cause constriction rings or extremity amputations. In contrast, cleft lip and palate are caused by embryologic fusion failure much earlier in fetal development. (Choice C) Conditions with mitochondrial inheritance are transmitted only by affected females to all of their offspring; therefore, a father would have no family history of the condition. Examples include mitochondrial myopathies, myoclonic epilepsy, and Leber hereditary optic neuropathy. (Choice E) In genetically normal (46, XX) female patients, a single X chromosome is normally randomly deactivated in each cell during early embryonic development. In rare cases, uneven inactivation of maternal/paternal X chromosomes (ie, skewed X-inactivation) may result in female offspring developing an X-linked recessive condition. In these conditions, an affected father with a female offspring would be expected. Educational objective: Most cases (approximately two-thirds) of cleft lip with cleft palate have multifactorial inheritance related to complex interactions of polygenetic and environmental factors.

A Primigravid Woman at 22 Weeks Gestation Comes to the Office