2025 – PAGE 266 – GENETICS & INHERITED DISEASES

HOLT ORAM SYNDROME

Holt Oram Syndrome findings include upper limb and cardiac defects. Look for an ABSENT (or HYPOPLASTIC) radius and thumb, TRIPLE-jointed thumb, and/or septal defects (ASD or VSD).

MNEMONICS: Imagine using your TRIPLE-JOINTED THUMB to take out a JOINT of marijuana from your mouth. You put it out on your ARM and create a HOLE (a “HOLED ARM”). Or, just say “Heart Arm” syndrome.

KEY: For the first mnemonic, the JOINT reminds you that there is a joint issue. “HOLED ARM” can remind you of Holt Oram and septal defects. The ARM reminds you of the potential absent, or hypoplastic, radius.

CRI-DU-CHAT SYNDROME (AKA 5p-, 5p minus or 5p DELETION SYNDROME)

Cri-Du-Chat Syndrome (AKA 5p-, 5p minus or 5p deletion syndrome) findings include a high-pitched cry, developmental delay, microcephaly, wide-set eyes (hypertelorism), a high palate, and possibly a VSD. The name means “cry of a cat.” Cries sound like the meow of a cat.

IMAGE: www.pbrlinks.com/CRIDUCHAT1

CROUZON SYNDROME (AKA CRANIOFACIAL DYSOSTOSIS)

Crouzon syndrome (AKA craniofacial dysostosis) findings include craniosynostosis (early suture closure), with a prominent forehead, proptosis, a cleft lip/palate, and the lack of syndactyly. Early suture closure usually refers to closure at < 6 months of age.

PEARL: Early suture closure also happens in Apert Syndrome (“A PEAR”), but there is no fusion of digits (syndactyly) in Crouzon. Also, there is some variability in the appearance of children with Crouzon Syndrome based on WHICH sutures close early.

IMAGE: www.pbrlinks.com/CROUZON1
IMAGE: www.pbrlinks.com/CROUZON2

MNEMONIC: Remember the pink plate (palate) with CROUTONS on it from the mnemonic earlier?

MNEMONIC: Sorry for any weak stomachs. Imagine a person who is missing eyes and has a cleft palate. You put two SUTURES in the FOREHEAD of the patient above the eyebrows. You leave some extra SUTURE material and then SUTURE through two CROUTONS as well and let them hang in front of the empty eye sockets (CROUTON EYES). You then take some crushed CROUTONS and shove them into the CLEFT PALATE to make it nice and even.

• KEY: SUTURES represent craniosynostosis, FOREHEAD represents a prominent forehead, CROUTON EYES represent proptosis and the filling of the cleft with croutons should help solidify the finding of cleft lip/palate in patients with Crouzon’s.

ANGELMAN SYNDROME (AKA ANGELMAN’S SYNDROME)

Angelman syndrome (AKA Angelman’s syndrome) patients can be MALE or FEMALE so don’t let the name fool you! These patients tend to be happy, “angelic” and laugh frequently. They are developmentally delayed, and have delayed speech. They are easily excited, can have seizures, and are ataxic with what is referred to as a “puppet gait.” The disorder results from the absence or the dysfunction a gene on the MATERNAL copy on chromosome 15. It’s a special type of gene. In normal children, both maternal and paternal copies function but they have DIFFERENT effects. If the maternal copy is MISSING, or dysfunctional, or if it has a mutation that makes it behave like the PATERNAL gene (called paternal imprinting), then Angelman Syndrome develops. Also, if the child gets TWO paternal copies of chromosome 15 (paternal disomy) and NO maternal copies of chromosome 15, then Angelman Syndrome develops. The gene location is probably not important for the test, but the fact that it is KNOWN means that this disorder can be diagnosed by FISH.

PEARL: The “puppet gait” terminology may have fallen out of favor but refers to an unstable and jerky gait like that of a puppet. The concept of unilateral parental disomy can be confusing. This is a great exam question for the pediatric boards. Hopefully the mnemonic below helps.

MNEMONIC: Rename the disease from AngelMAN to AngelWOMAN to remind you that it can ALSO occur in females.

MNEMONIC: Imagine a FEMALE ANGEL with wings. She has a SMILE on her face and is wearing a t-shirt that says “DADDY’S LITTLE ANGEL.” Even though she has wings, the man upstairs decides he is going to pull her to the clouds with some PUPPET STRINGS.

• KEY: FEMALE ANGEL represents that this is a male OR female disorder, SMILE represents frequent laughter, DADDY’S LITTLE ANGEL represents paternal disomy in which she is carrying two sets of Dad’s genes, and the PUPPET STRINGS is to remind you of the “puppet gait.”