Down Syndrome/Trisomy 21 Full trisomy 21 94% Mosaic trisomy 21 2.4% Translocation 3.3% Translocations Parent carrier t(21q;21q) 100% recurrence Parent carrier t(14q;21q)1/3 chance of having affected child Heart defect: Endocardial cushion defect Special Olympics: Atlantoaxial instability IF THE PATIENT HAS A TRANSLOCATION THE PARENTS KARYOTYPE SHOULD BE CHECKED
Risk Table for Down Syndrome Maternal AgePrevalence at Live Birth 251/1350 301/890 351/355 401/97 451/23 Note from Caroline: You need to know these numbers cold! Note from Rachel: I’d rather memorize developmental milestones or stick a fork in my eye!
CRANIOSYNOSTOSIS premature fusion of 1 or more cranial sutures, often resulting in an abnormal head shape Simple 1 fused suture Complex > 1 suture Syndromic Complex+other malformations Should be recognized before 5 mo of age
The craniofacial syndrome associated with cervical spine fusion, OM, and syndactyly. – Aperts 71% of patients with this CFS have Chiari I type malformations and hydrocephalus – Crouzon What cutaneous finding is associated with Crouzon syndrome? – Acanthosis nigricans Which CFS is associated with medially deviated great toes & broad radial thumbs? – Pfeiffer Syndrome
You see a baby in the NICU with feet like this… What lab test would confirm the diagnosis? Chromosomes (45, XO)
Turner Syndrome / 45,X0 It is the most common chromosomal defect in spontaneous abortions Short stature, webbed neck, delayed secondary sexual characteristics, short 4 th -5 th metacarpals, widely space nipples, pedal edema, cubitus valgus Most common cardiac defect in TS Coarctation of the aorta.
Edwards Syndrome/Trisomy 18 Rocker bottom feet Clenched fists, hypoplastic nails Short sternum, prominent occiput, microcephaly. Horseshoe Kidney
Inheritance Autosomal Dominant Diagnostic criteria: Abnormalities of the thumb triphalangia hypoplasia aplasia Congenital heart disease. atrial septal defects arrhythmia Holt-Oram Syndrome
A 4 year old boy presents because he’s been falling a lot per his parents. His dad is mad because the child “walks like a girl on his tippy toes.” What diagnosis should you suspect? – Duchenne’s Muscular Dystrophy Can someone demonstrate a physical exam finding seen in this disease? – Gower sign What would be the diagnostic finding on muscle biopsy? – Absence of dystrophin
Duchenne Muscular Dystrophy Gower sign Pseudohypertrophy of the calves Duchenne Muscular dystrophy is the most common hereditary muscular disease, a X linked recessive disorder inherited by more than 1:4000 boys.
Patient started having difficulties in school when he was eight years old. His teacher noted that he seemed to be irritable and impulsive; she raised the possibility of attention deficit disorder. In addition, Ronnie was noted to have mild difficulties with spelling and composition. Although he was requiring some additional help with these tasks, his IQ was normal (104) and he had been progressing academically with his peer group. He was tall for his age (95th percentile in height). He had no physical or medical problems. A detailed evaluation by a psychologist revealed some impulsivity, but insufficient findings to support a diagnosis of attention deficit disorder. Tutoring was arranged, and he continued to progress adequately in school. At age 14 years, he develops gynecomastia. At this point, he is seen by an endocrinologist. What is the diagnosis ? Klinefelter Syndrome Treatment: TESTOSTERONE
You also need to know Normal testicular volume Age, yr Length, cm (mean ± SD) Volume, mL (approximate) < 21.4 ± 0.4 2 - 41.2 ± 0.2 4 - 61.5 ± 0.61 6 - 81.8 ± 0.3 8 - 102.0 ± 0.52 10 - 122.7 ± 0.75 12 - 143.4 ± 0.810 14 - 164.1 ± 1.020 16 - 185.0 ± 0.529 18 - 205.0 ± 0.329
McCune Albright Syndrome Café au Lait spot with irregular borders like the coast of Maine polyostotic fibrous dysplasia : abnormal fibrous tissue growth in many bones. Normal bone is replaced by irregular masses of fibroblast cells. Precocious Puberty Appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal Males <9 years Females < 8 years
Cri du Chat/ Deletion 5p One of the most common human deletion syndromes with an incidence 1 in 20,000 to 1 in 50,000 births The syndrome was discovered in France in 1963 by a team headed by the late Jerome Lejeune. The peculiar cry of affected infants sounded to Lejeune like the meowing of a Parisian cat. The syndrome involves severe developmental and mental retardation and a characteristic constellation of congenital malformations: microcephaly round face hypertelorism micrognathia epicanthal folds low-set ears hypotonia motor and mental retardation Although the majority of patients die in early childhood, some survive into adulthood and exhibit an IQ below 20.
This girl has hearing problems but otherwise does well in school. What is her diagnosis? Treacher Collins What might clue you in on family history? Multiple family members with hearing aids
Noonan Syndrome Clinical Features Short stature Congenital heart defect (Pulmonary Stenosis) Webbed neck Superior pectus carinatum, inferior pectus excavatum, Apparently low-set nipples; Developmental delay of variable degree; Cryptorchidism; Characteristic facies: low-set, posteriorly rotated ears; vivid blue or blue-green irises; wide-spaced eyes with epicanthal folds thick or droopy eyelids. Coagulation defects AKA as Male Turner, but don’t be fooled it can be present in females due to AD inheritance. 3 genes associated: PTPN11, KRAS, SOS1
You have an obese 6 year old male who was brought in because his mom is frustrated that he is always waking up and stealing food from the kitchen at night even though he’s on a diet. What is the mechanism of action for the diabetes he will likely develop? – It’s type 2 DM due to insulin resistance What other complications is he at risk for? – GH deficiency, hypogonadism, osteoporosis, hypothyroidism, SCFE, sleep apnea….
Clinical Features Severe DDM Profound speech impairment Ataxia and other movement disorders Inappropriate laughter Short attention span Microcephaly and seizures Wide spaced teeth Hypopigmentation Angelman Syndrome Remember IMPRINTING 2 alleles from MOM PWS 2 alleles from DAD AS
Clinical Features Macroglossia Omphalocele Macrosomia Hypoglycemia Hemihypertrophy Hypospadias Indentation on posterior helix Beckwith Wiedemann Syndrome
Inheritance autosomal dominant Clinical Features aplasia or hypoplasia of the thymus (immunodeficiency) aplasia, or hypoplasia of the parathyroid glands (Hypocalcemia) conotruncal cardiac defects Hearing loss, CL/CP, velopharyngeal incompetence, prominent nose, narrow alae nasi, long face Slender fingers DiGeorge Syndrome/ Deletion 22q11.2/VCF VSD (62%) R AoArch (52%), TOF (21%) What lab test makes the diagnosis: FISH 22q
You would use FISH to detect all of the following syndromes except: A.Prader willi B.Edwards C.Velocardiofacial D.Williams E.Cri du chat All of them are deletions except Edwards (check chromosomes)
Mental retardation, dysmorphic facies, infantile hypercalcemia, growth deficiency, cocktail personality, hoarse voice, enamel hypoplasia Williams Syndrome Supravalvular Ao stenosis
Prenatal and postnatal growth delay Neurodevelopmental deficits Long philtrum Thin/smooth upper lip Short palpebral fissures Epicanthal folds mid face hypoplasia Mild to moderate microcephaly Short nose Fetal Alcohol Syndrome