Isotretinoin-like syndrome is a phenocopy of the isotretinoin embryopathy. It has been described in six male patients, three of them being siblings born to nonconsanguineous parents. It has characteristics of the same anomalies as those described after maternal treatment with the drug isotretinoin: malformations of the face (small, malformed, or missing ears, micrognathia, cleft palate), conotruncal heart defects, aortic arch anomalies, and central nervous system anomalies (hydrocephalus and posterior fossa abnormalities). As the syndrome has only been reported in males, X-linked recessive inheritance is possible but autosomal recessive inheritance cannot be ruled out.

Microtia-anotia (M-A) can occur either as an isolated defect or in association with other defects. Only in a minority of cases has a genetic or environmental cause been found; in these cases, M-A is usually part of a specific pattern of multiple congenital anomalies. For instance, M-A is an essential component of isotretinoin embryopathy (243440), is an important manifestation of thalidomide embryopathy, and can be part of the prenatal alcohol syndrome and maternal diabetes embryopathy. M-A occurs with a number of single gene disorders, such as Treacher Collins syndrome (154500), branchiootorenal/branchiootic syndromes (see 113650 and 602588), oculoauricular syndrome (612109), microtia with hearing impairment and cleft palate (612290), or chromosomal syndromes, such as trisomy 18. M-A also occurs as part of seemingly nonrandom patterns of multiple defects, such as Goldenhar syndrome (164210) (Mastroiacovo et al., 1995). Alasti and Van Camp (2009) reviewed the genetics of microtia and microtia-associated syndromes and discussed their clinical aspects in relation to the causative genes. They stated that the estimated prevalence of microtia is 0.8 to 4.2 per 10,000 births, that it is more common in males, and that it can have a genetic or environmental predisposition. Reviews Ronde et al. (2023) reviewed the international classification and clinical management strategies for craniofacial microsomia and microtia (CFM; see 164210), and tabulated survey responses from 57 professionals involved in management of CFM patients. The authors noted that although the International Consortium for Health Outcomes Measurement (ICHOM) criteria for CFM exclude isolated microtia from the phenotypic spectrum of CFM, the question of whether isolated microtia can be considered the mildest form of CFM is debated in the literature. No consensus was reached in their survey, as a majority of respondents agreed with the ICHOM criteria but also considered isolated microtia to be a mild form of CFM.

Treacher Collins syndrome (TCS) is characterized by bilateral and symmetric downslanting palpebral fissures, malar hypoplasia, micrognathia, and external ear abnormalities. Hypoplasia of the zygomatic bones and mandible can cause significant feeding and respiratory difficulties. About 40%-50% of individuals have conductive hearing loss attributed most commonly to malformation of the ossicles and hypoplasia of the middle ear cavities. Inner ear structures tend to be normal. Other, less common abnormalities include cleft palate and unilateral or bilateral choanal stenosis or atresia. Typically intellect is normal.

Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA.

Craniofacial microsomia is a term used to describe a spectrum of abnormalities that primarily affect the development of the skull (cranium) and face before birth. Microsomia means abnormal smallness of body structures. Most people with craniofacial microsomia have differences in the size and shape of facial structures between the right and left sides of the face (facial asymmetry). In about two-thirds of cases, both sides of the face have abnormalities, which usually differ from one side to the other. Other individuals with craniofacial microsomia are affected on only one side of the face. The facial characteristics in craniofacial microsomia typically include underdevelopment of one side of the upper or lower jaw (maxillary or mandibular hypoplasia), which can cause dental problems and difficulties with feeding and speech. In cases of severe mandibular hypoplasia, breathing may also be affected.\n\nPeople with craniofacial microsomia usually have ear abnormalities affecting one or both ears, typically to different degrees. They may have growths of skin (skin tags) in front of the ear (preauricular tags), an underdeveloped or absent external ear (microtia or anotia), or a closed or absent ear canal; these abnormalities may lead to hearing loss. Eye problems are less common in craniofacial microsomia, but some affected individuals have an unusually small eyeball (microphthalmia) or other eye abnormalities that result in vision loss.\n\nAbnormalities in other parts of the body, such as malformed bones of the spine (vertebrae), abnormally shaped kidneys, and heart defects, may also occur in people with craniofacial microsomia.\n\nMany other terms have been used for craniofacial microsomia. These other names generally refer to forms of craniofacial microsomia with specific combinations of signs and symptoms, although sometimes they are used interchangeably. Hemifacial microsomia often refers to craniofacial microsomia with maxillary or mandibular hypoplasia. People with hemifacial microsomia and noncancerous (benign) growths in the eye called epibulbar dermoids may be said to have Goldenhar syndrome or oculoauricular dysplasia.

The Cincinnati type of acrofacial dysostosis is a ribosomopathy characterized by a spectrum of mandibulofacial dysostosis phenotypes, with or without extrafacial skeletal defects (Weaver et al., 2015). In addition, a significant number of neurologic abnormalities have been reported, ranging from mild delays to refractory epilepsy, as well as an increased incidence of congenital heart defects, primarily septal in nature (Smallwood et al., 2023).