Genetic Conditions Organized by Presenting Symptoms Flashcards
Chromosomal instability syndromes most commonly have what pattern of inheritance?
Autosomal recessive
What are chromosomal instability syndromes?
A group of disorders that are largely autosomal recessive and have an increased frequency of chromosomal breaks.
List four chromosomal instability syndromes.
Ataxia-telangiectasia, Bloom syndrome, Fanconi syndrome, and xeroderma pigmentosum.
What is the most common craniofacial malformation?
Cleft lip and/or cleft palate
Which ethnic group has the highest rates of cleft lip/palate? The lowest rates?
Native Americans have the highest rates of cleft lip/palate, while African Americans have the lowest rates.
What is the definition of a sequence as it relates to congenital anomalies?
A sequence refers to a pattern of anomalies that result from a single identifiable event in development. It does not necessarily have an underlying genetic abnormality.
What is the primary embryologic defect in patients with Pierre Robin sequence?
Mandibular hypoplasia.
Describe the sequence progression and resultant physical abnormalities associated with Pierre Robin sequence.
Mandibular hypoplasia > tongue displacement > interrupted closure of the lateral palatine ridges > U-shaped cleft palate. On exam, this presents as micrognathia, retrognathia, glossoptosis (displacement of the tongue into the airway), respiratory distress, and feeding problems. Respiratory distress can lead to pHTN.
What is the amniotic band sequence?
Absence or malformation of a body part due to amniotic band adherance during fetal development. This can present as disruptive clefts of the face and palate, constriction rings of the limbs and/or digits, and amputations.
What is the relationship between hemifacial microsomia and Goldenhar syndrome?
Goldenhar and hemifacial microsomia are considered to be the same disorder, but the term “Goldenhar syndrome” is used only if epibulbar dermoids are present.
What is hemifacial microsomia?
It is the association of external ear anomalies (microtia, anotia, canal atresia, and/or preauricular tags) with maxillary and/or mandibular hypoplasia.
List 3 congenital anomalies which can occur in conjunction with hemifacial microsomia.
Cervical vertebral anomalies, cardiac defects, and renal anomalies.
Describe the findings typical of a patient with Goldenhar syndrome.
Hemifacial microsomia (external ear abnormalities + maxillary and/or mandibular hypoplasia), epibulbar lipodermoids (lateral-inferior fibrous-fatty masses on the globe), vertebral defects, cardiac anomalies, and renal anomalies.
What syndrome is characterized by branchial cleft fistulas or cysts, preauricular pits, cochlear and stapes malformations, mixed sensory and conductive hearing loss, and renal dysplasia/aplasia?
Branchio-Oto-Renal syndrome.
What is the inheritance pattern for Branchio-Oto-Renal syndrome?
Autosomal dominant
Describe the features typical of patients with Treacher-Collins syndrome.
Micrognathia, zygomatic arch clefts, various forms of ear malformations, down-sloping palpebral fissures, and colobomata of the lower eyelids. Conductive hearing loss is often present as well.
What is the inheritance pattern in Treacher-Collins syndrome?
Autosomal dominant
Define craniosynostosis.
The early, pathologic fusion of calvarial sutures.
What is the most common suture involved in single-suture craniosynostosis?
The saggital suture.
What is the male:female ratio for isolated saggital craniosynostosis?
5:1 male:female ratio
List, in descending order of frequency, the four types of single-suture craniosynostoses.
Saggital > coronal > metopic > lambdoid
What type of head growth is seen with early fusion of the saggital sutures?
Saggital craniosynostosis results in excessive anterior/posterior growth with a resulting long, narrow head shape with frontal and occipital prominence. This is known as scaphocephaly or dolichocephaly. ***Pic?
What type of head growth is seen with early fusion of the coronal or sphenofrontal sutures?
Coronal craniosynostosis results in unilateral flattening of the forehead, elevation of the ipsilateral orbit and eyebrow, and a prominent ear on the affected side, known as frontal plagiocephaly. ***Pic?
Which forms of craniosynostosis are more common in females?
Coronal and sphenofrontal craniosynostosis
What type of head growth is seen with early fusion of the metopic sutures?
Metopic craniosynostosis results in a keel-shaped forehead and hypotelorism, known as trigonocephaly. ***Pic?
What is the appearance of an infant with early fusion of the coronal, sphenofrontal, and frontoethmoidal sutures? What is the name for this head shape?
This combination of synostoses results in a cone-shaped head, known as turricephaly. ***Pic?
What is positional plagiocephaly?
The postnatal flattening of the skull that is caused by the infant’s preference of sleeping/resting position.
Where would you expect to see flattening of the skull in infants with plagiocephaly due to torticollis?
These infants typically have flattening of the occipitoparietal area.
What form of craniosynostosis can have a similar clinical appearance as that of plagiocephaly?
Lambdoid craniosynostosis
How would one differentiate between positional plagiocephaly and lambdoid craniosynostosis on exam?
The ipsitateral ear is displaced anteriorly in positional plagiocephaly vs posterior/inferior for lambdoid synostosis; ipsilateral frontal prominence is present in plagiocephaly but not synostosis; contralateral occipitoparietal prominence is present in lambdoid synostosis but not plagiocephaly; lambdoid ridge and submastoid prominences are seen in synostosis but not plagiocephaly; positional plagiocephaly stops progressing after 7 months because children aren’t lying on their heads as often, while lambdoid synostosis continues to progress after 7 months.
What is the most common type of skeletal dysplasia?
Achondroplasia
Describe the findings in achondroplasia.
Disproportionately short stature with rhizomelic shortening (short lengths of the most proximal (“root”) segments of the upper arms and legs compared to the distal segments), lumbar lordosis, trident hands, macrocephaly, and characteristic facial findings (flat nasal bridge, prominent forehead, and midface hypoplasia). ***Image 22-11
What is the inheritance pattern in achondroplasia, and what gene is responsible?
It is an autosomal dominant disorder in which most individuals have a de novo mutation of FGFR3 (fibroblast growth factor receptor 3) on chromosome 4p16.3.
What risk factor is associated with increased risk for a child being born with achondroplasia?
Increased paternal age
What skull structural abnormality can occur in infants with achondroplasia?
Foramen magnum stenosis and/or craniocervical junction abnormalities can occur in infancy and cause compression of the upper cord - resulting in apnea, quadriparesis, growth delay, and hydrocephalus.
List 5 x-ray findings characteristic of individuals with achondroplasia.
Squared-off iliac wings, flat and irregular acetabulum roofs, thick femoral necks, “ice-cream scoop” shaped femoral heads, and rhizomelic shortening.
What are the thanatophoric dysplasias?
There are two types (1 and 2), which are both caused by FGFR3 mutations. Most cases are lethal, but those who survive to infancy present with macrocephaly with very short limbs.
What physical exam findings can help to differentiate between Thanatophoric Dysplasia Type 1 and Type 2?
Individuals with Type 1 have bowed femurs, while those with Type 2 have straight femurs. Type 2 infants also have a “cloverleaf” skull caused by premature closure of the sagittal, coronal, and lambdoid sutures.
List 3 characteristic x-ray findings associated with Thanatophoric Dysplasia.
Platyspondyly (flatness of the body of the vertebrae), flared metaphyses of the long bones, and short iliac bones. Individuals with Type 1 have bowed femurs as well.
