Developmental Genetics and Birth Defects Flashcards
Cutaneous syndactyly
cryptoopthalamos
GU anomalies
renal agenesis
Fraser Syndrome
FRAS1, FREM2, GRIP1
Autosomal recessive
Post-axial polydactyly
dwarfism
short forearms
malformed fingernails and toenails
Ellis-van-Creveld
Chondroectodermal dysplasia
EVC EVC2 (Regulation of the SHH pathway)
Multiple dislocated joints
clubfeet
extrabones in hands and feet
spatulate blunt thumbs
frontal bossing
hearing loss
midfacehypoplasia, cleft palate
Larsen Syndrome
FLNB
AR
Pre-axial polydactyly
Duplicated thumbs
Abnormal cupped ears
imperforate anus
Townes-Brocks
SALL1
fine, sparse, depigmented, and slow growing hair; dystrophic nails; and small breasts
short stature; short feet; brachydactyly with ulnar or radial deviation of the fingers; and early, marked hip dysplasia
Trichorhinophalangeal syndrome (TRPS I)
TRPS1
TRPS II - TRPS II (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). characterized by multiple osteochondromas
rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities
Bardet-Biedl
Mutations in BBS genes lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during development and lead to abnormalities of sensory perception.
About one-quarter of all cases of Bardet-Biedl syndrome result from mutations in the BBS1 gene. Another 20 percent of cases are caused by mutations in the BBS10 gene.
preaxial polydactyly of the feet and postaxial polydactyly of the hands plus syndactyly of fingers 3-4 and toes 1-3).
wide spaced eyes
Macrocephaly
Greig Cephalopalysyndactyly
- GLI3*
- Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome. This gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells.*
- Part of the SHH pathway*
Central or post-axial polydactyly
hypothalamic hamartoma
bifid epiglottis
laryngeal cleft
pulmonary segmentation anomalies
Pallister Hall Syndrome
GLI3 , frameshift/nonsense truncating mutations
Autosomal recessive
unilateral absence of the pectoralis minor and the sternal or breastbone portion of the pectoralis major
absence of upper ribs; elevation of the shoulder blade (Sprengel deformity); and/or shortening of the arm
symbrachydactyly
Poland sequence/Syndrome
prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability
cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes
Smith-Lenli-Opitz Syndrome
elevated serum concentration of 7-DHC
DHCR7 is the only gene in which pathogenic variants are known to cause SLOS. Sequence analysis of DHCR7 detects approximately 96% of known pathogenic variants
congenital hemidysplasia with ichthyosiform nevus and limb defects
unilateral distribution of ichthyosiform (yellow scaly) skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal.
CHILD syndrome
X-linked condition that is usually male lethal during gestation and thus predominantly affects females
NSDHL pathogenic variant that results in loss of functional NSDHL protein
Pierre Robin sequence with cleft palate, shortening and bowing of long bones, and clubfeet
ambiguous genitalia or normal female external genitalia in most individuals with a 46,XY karyotype.
Campomelic Dysplasia
SOX9
SRY-related HMG-box gene 9 (SOX-9)
form of polydactyly consists of duplication of the distal phalanx, giving a ‘duck-bill’ appearance
duplication encompassing the limb-specific regulatory element (ZRS) of sonic hedgehog SHH, which lies in intron 5 of the `limb region 1 homolog’ gene, LMBR1 (7q36)
Triphalangeal thumb-polysyndactyly syndrome (TPT-PS)
autosomal dominant osteochondrodysplasia characterized by disproportionate short stature, deformity of the lower limbs, brachydactyly, loose joints, and ligamentous laxity. Vertebral anomalies, present in childhood, usually resolve with age, but osteoarthritis is progressive and severe.
Psuedoachondroplasia
COMP
myopia, cataract, and retinal detachment;
hearing loss (conductive and sensorineural)
midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence)
mild spondyloepiphyseal dysplasia and/or precocious arthritis.
Stickler Syndrome
- COL2A1 :* encodes the chains of type II collagen, a major structural component of cartilaginous tissue
- COL11A1 :* encodes for the alpha 1 chain of type XI collagen. It is presumed to play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
