Neotenic complex syndrome (NCS) is a

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...

that presents as an extreme form of

developmental delay The term developmental delay can refer to: *Global developmental delay, an umbrella term used when children are significantly delayed in two or more areas of development *Specific developmental disorder, a classification of disorders characterize ...

, with the defining characteristic being

neoteny Neoteny (), also called juvenilization,Montagu, A. (1989). Growing Young. Bergin & Garvey: CT. is the delaying or slowing of the Physiology, physiological, or Somatic (biology), somatic, development of an organism, typically an animal. Neoteny i ...

of the patient. It was named in 2017 by Dr. Richard F. Walker, who discovered several genes implicated in the syndrome. Prior to 2015, when

whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing or just genome sequencing, is the process of determining the entirety of the DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's ...

was used to identify some genes involved in NCS, the condition was labelled "Syndrome X" when it was first discovered in Brooke Greenberg. Thereafter, others with the developmental symptoms were sought out in order to find common genetic aberrations that could provide clues as to cause. To date, seven human females have been diagnosed with NCS. In five patients, coding ''de novo'' mutations were found in five different

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s which fall into similar functional categories of

transcription regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...

and

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

modification.

Genetics

In most of the patients analyzed, researchers identified

missense In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn al ...

''de novo'' mutations in a set of genes. Mutations in three of these genes (''

DDX3X ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the ''DDX3X'' gene. Function DEAD box proteins are putative RNA helicases characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD). They are implicated in a numb ...

'', '' TLK2'' and '' HDAC8'') were shared with those found in databases of individuals with developmental delay or

autism spectrum disorder Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing di ...

. A mutation in one gene (''TMEM63B'') was identified in a large

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

study as likely to result in disease in humans. In two patients, a small (~150 kb)

non-coding Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regula ...

region of

chromosome X The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

was discovered to have a rare haplotype. This region appears to have regulatory functions ( histone acetylation and DNase I hypersensitivity) and is in close proximity to several genes (''AP1S2'', ''MRX59'', ''MRXSF'', ''MRXS21'', ''MRXS5'' and ''PGS'') involved in mental retardation. The fact that NCS has so far only been found in females may be by chance or may be due to the

X linkage Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). Genes situated on the X-chromosome are thus termed X-linked, and a ...

of some of the genes and regions potentially responsible for NCS, in which the lack of a healthy copy on a second X chromosome could render the disease lethal in males. Whether or not these mutations contribute to NCS is unclear. Not enough research has been conducted, complicated by the rarity of the syndrome. Many genetic differences were noted to be insignificant, and the effects of mutations in some genes are currently beyond scientific understanding.

History

An 1888 article in the newspaper ''The Diamond Drill'' of Crystal Falls,

Michigan Michigan ( ) is a peninsular U.S. state, state in the Great Lakes region, Great Lakes region of the Upper Midwest, Upper Midwestern United States. It shares water and land boundaries with Minnesota to the northwest, Wisconsin to the west, ...

, describes a 17-year-old girl from

Stockerau Stockerau () is a town in the district of Korneuburg (district), Korneuburg in Lower Austria, Austria. Stockerau has 16,974 inhabitants, which makes it the largest town in the Weinviertel. Stockerau is also called "Lenaustadt" (Lenau Town) because ...

Vienna Vienna ( ; ; ) is the capital city, capital, List of largest cities in Austria, most populous city, and one of Federal states of Austria, nine federal states of Austria. It is Austria's primate city, with just over two million inhabitants. ...

, named Maria Schumann. Due to her condition (identified at the time as "

microcephaly Microcephaly (from Neo-Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it m ...

"), she had never outgrown the mental state or size of an infant, but was of "sound composition". She could not speak or masticate, consumed only liquids and pulpy foods despite having all of her teeth, and often slept for 2 days and 2 nights at a time.

Prominent cases

* Brooke Greenberg

References

{{reflist, refs= {{cite journal, last1=Walker, first1=Richard F., last2=Liu, first2=Jia Sophie, last3=Peters, first3=Brock A., last4=Ritz, first4=Beate R., last5=Wu, first5=Timothy, last6=Ophoff, first6=Roel A., last7=Horvath, first7=Steve, title=Epigenetic age analysis of children who seem to evade aging, journal=Aging (Albany NY), date=May 15, 2015, volume=7, issue=5, pages=334–339, doi=10.18632/aging.100744, pmc=4468314, pmid=25991677 {{cite journal, last1=Walker, first1=Richard F., last2=Ciotlos, first2=Serban, last3=Mao, first3=Qing, last4=Chin, first4=Robert, last5=Drmanac, first5=Snezana, last6=Barua, first6=Nina, last7=Agarwal, first7=Misha R., last8=Rebecca, first8=Yu Zhang, last9=Zhenyu, first9=Li, last10=Ka Yan Wu, first10=Michelle, last11=Sun, first11=Kevin, last12=Lee, first12=Katharine, last13=Nguyen, first13=Staci, last14=Liu, first14=Jia Sophie, last15=Carnevali, first15=Paolo, last16=Drmanac, first16=Radoje, last17=Peters, first17=Brock A., title=Clinical and genetic analysis of a rare syndrome associated with neoteny, journal=Genetics in Medicine, date=September 21, 2017, volume=20, issue=5, pages=495–502, doi=10.1038/gim.2017.140, pmid=29758565, doi-access=free Neurogenetic disorders Rare genetic syndromes Growth disorders Specific developmental disorders