Overgrowth Flashcards
What is hyperphagia
Excessive hunger/overeating
What are causes of obesity?
Hyperphagia
Short Stature
Low tone
Food quality
MC4R deficiency
“Semidominant”–partial phenotype with one copy, severe phenotype with both
Recessive form: hyperphagia, extreme obesity, early onset
2-5% of total early onset obesity
Dominant: Hyperphagia, binge eating
Which disorder has hyperphagia and early onset obesity, frequent infections, hypogonadotropic hypogonadism, and hypothyroidism?
Leptin Deficiency
Dominant form: Hyperphagia and early onset obesity
AR: also has frequent infections, hypogonadotropic hypogonadism, and hypothyroidism
Treatable with leptin replacement
Which disorder accounts for 3% of cases with severe obesity?
Leptin Receptor Deficiency
In which disorder are patients usually pale and red-headed, present with adrenal insufficiency (low BP, salt wasting) and prolonged jaundice
POMC deficiency (AR)
Pro-opio-melano-cortin
Melano-patient usually pale and red-headed
Cortin-corisol; presents with adrenal insufficiency (low BP, salt wasting) and prolonged jaundice
Which disorder has malabsorptive diarrhea, low blood sugar after eating, obesity
PSCK1 Deficiency (AR)
PSCK1 processes propeptide hormones into their mature form
What are some causes of macrosomia?
Infant of Diabetic Mother
Beckwith Wiedemann
Sotos syndrome
NFIX related disorders
Weaver syndrome
PTEN-hamartoma syndrome
Simpsom Golabi Behmel
Gorlin
Perlman
What is macrosomia?
Increased height, weight, and head size (>97th %tile)
What are the results of diabetes in a pregnant person (mild cases)?
Birthweight >4kg
Low blood sugar due to high levels of circulating insulin
Prolonged jaundice, high blood counts
Septal hypertrophy of the heart
Long term outcome is good
What are the results of diabetes in a pregnant person (severe cases)?
Birthweight > 4kg
Holoprosencephaly
Caudal regression syndrome
Proximal femoral deficiency
What are the main characteristics of Beckwith Wiedemann syndrome?
Fetal overgrowth
Omphalocele
Internal organ overgrowth
Hemihyperplasia
Macroglossia
Proptosis
Prolonged hypoglycemia
Risk of Wilms tumor and hepatoblastoma (screen every 3 mos)
What are the screening guidelines for BWS?
AFP every 3 months for first 4 years of life (have to BWS-based values–AFP is much higher at baseline)
Renal ultrasound every 3 months for first 8 years (then annually till mid-adolescence)
What percentage of Sotos syndrome is caused by LoF mutations?
90%
In Japan whole gene deletions more likely
What is the phenotype of Sotos syndrome?
Increased birthweight
Continued increased height
Advanced bone age
Large, narrow head
Bossing of forehead, bitemporal narrowing
Receding hairline
In time, elongated chil
What is the phenotype of Sotos?
Neonatal hypotonia
Birth anomalies (PDA, ASD, renal, scoliosis)
50% seizures
Feeding difficulties –> sometimes present as FTT
DD (clumsy with poor coordination)
97% with ID (30% mild, 40% mod, 20% severe)
What is the tumor risk for Sotos syndrome?
3% risk for tumors
- Neuroblastoma
- Sacrococcygeal teratoma
- Presacral ganglioneuroma
- Acute lymphocytic leukemia
- Small cell lung cancer
Tumor screening not effective for early detection or intervention
What is the genetic cause of Marshall-Smith?
NFIX (AD)
De novo
What is the phenotype of Marshall-Smith syndrome?
Large body size
Accelerated bone age
Dysmorphic findings
-Connective tissue-like
-Hypermobility
-Blue Sclerae
FTT
Macrocephaly, high forehead
Proptosis/prominent eyes
Short nose, underdeveloped midface, long narrow face
Micrognathia
Resp problmes/laryngomalacia
Decreased muscle mass
CC abnormality
ID
What is the genetic cause of Weaver syndrome?
EZH2 (AD)
What is the phenotype of Weaver syndrome?
Similar to Sotos (typically milder ID)
20% with normal intelligence
Overgrowth, advanced bone age
Camptodactyly
Fleshy ears, micrognathia, “stuck-on” chin
Tumor frequency ~4%
- neuroblastoma, acute lymphoblastic leukemia, ovarian endodermal sinus tumor, sacrococcygeal teratoma, and lymphoma
- no tumor screening
What is the phenotype of PTEN Harmartoma syndrome?
Macrosomia, but with normalized height
Head remains large (+5SD)
Skin
What is the phenotype of PTEN Harmartoma syndrome?
Macrosomia, but with normalized height
Head remains large (+5SD)
Skin papules and lipomata
Autism + macrocephaly (+3 SD)
Widely variable presentation within families
What is the screening in patients with PTEN for children <18years?
Yearly thyroid US (from time of dx)
Skin check w/physical exam
What is recommended screening for women with PTEN
30 years:
Monthly breast self-examination
Annual breast screening (MRI or mammogram)
35 years:
Transvaginal US or endometrial biopsy
Colonoscopy (male as well)
40 years:
Renal imaging (q2y)(males as well)
Family hx:
Screening 5-10 years prior to youngest age of dx
What is the genetic change in Simpson Golabi Behmel syndrome?
GPC3 (X-linked LoF); Dup of GPC4 (2 cases)
What is the phenotype of Simpson Golabi Behmel syndrome?
Pre- and postnatal overgrowth (often with polyhydramnios)
Macrocephaly
Coarse facial features: hypertelorism, epicanthal folds, midline groove in lower lip
Postaxial polydactyly, syndactyly, broad hands, nail hypoplasia
Organomegaly, supernumerary nipples
CHD, Cardiac conduction defects
Cryptorchidism, hernia
Diaphragmatic hernia (~30%)
Cleft lip or palate (~25%)
ID from mild to severe
What tumor screening do you perform in Simpson Golabi Behmel syndrome?
Wilms
Hepatoblastoma
Same strategy as Beckwith Wiedemann syndrome
What are the genetic changes in Gorlin syndrome?
LoF in PTCH1 or SUFU
What is the minor criteria for Gorlin syndrome?
Macrocephaly
Childhood meduloblastoma (5%)
Lympho-mesenteric or pleural cysts
Cleft lip/palate
Vertebral/rib anomalies
Preaxial or postaxial polydactyly
Ovarian/cardiac fibromas
Ocular anomalies
What is the major criteria for Gorlin syndrome?
Calcification of the falx cerebi
Jaw keratocyst
Palmar/plantar pits (>=2)
Multiple basal cell carcinomas (>5 lifetime) or a BCC before age 30 years
First degree relative with NBCCS
What are the features of Perlman syndrome?
Polyhydramnios
Neonatal macrosomia
Visceromegaly
Renal dysplasia (cystic)
Nephroblastomatosis
Predisposition to Wilms tumor (64%)
Cryptorchidism
High neonatal mortality
ID
What is the genetic cause of Perlman syndrome?
DIS3L2 (AR)
What is the genetic cause of Proteus syndrome?
Somatic mosaic variant in AKT1
What is the phenotype of Proteus syndrome?
Disfiguring overgrowth
Cerebriform overgrowth of palms/soles (Moccasin soles)
