Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is a rare disorder that affects several parts of the body. It is characterized by a clouding of the lens of the eyes at birth (congenital cataracts) and other eye abnormalities, such as small or poorly developed eyes (microphthalmia) and abnormal eye movements (nystagmus). Affected individuals, particularly males, often have distinctive facial features that become more apparent as they reach adulthood. These features include a prominent midface, a large nose, protruding teeth, and a small lower jaw.

CCFDN causes progressive damage to the peripheral nerves, which connect the brain and spinal cord to muscles and sensory cells. This nerve damage is known as peripheral neuropathy. Weakness in the legs, followed by the arms, begins in the first few years of life, and as a result children with CCFDN have delayed development of motor skills such as standing and walking. In adolescence, affected individuals develop sensory abnormalities such as numbness and tingling, mainly in the legs. By adulthood they typically have significant difficulties with mobility. Muscle weakness can also lead to skeletal abnormalities such as hand and foot deformities and abnormal curvature of the spine.

People with CCFDN may have problems with balance and coordination (ataxia), tremors, and difficulty with movements that involve judging distance or scale (dysmetria). Some have mild intellectual disability. Individuals with CCFDN have short stature, are typically underweight, and have reduced bone density.

A complication called rhabdomyolysis occurs in some people with CCFDN, typically following a viral infection or, in rare cases, during or after surgery. Rhabdomyolysis is a breakdown of muscle tissue that results in severe muscle weakness. The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). The presence of myoglobin causes the urine to be red or brown. The muscles may take up to a year to recover, and the episodes may worsen the muscle weakness caused by the neuropathy.

The prevalence of CCFDN is unknown. The disorder has been identified in about 150 individuals of Romani ethnicity. Thus far, no affected individuals have been observed outside this community.

A mutation in the CTDP1 gene causes CCFDN. The CTDP1 gene provides instructions for making a protein called carboxy-terminal domain phosphatase 1. This protein helps regulate the process of transcription, which is a key step in using the information carried by genes to direct the production (synthesis) of proteins.

All known individuals with CCFDN have the same mutation in both copies of the CTDP1 gene in each cell. This mutation alters the way the gene's instructions are pieced together to produce the carboxy-terminal domain phosphatase 1 protein. The altered instructions introduce a premature stop signal, resulting in an abnormally short, nonfunctional protein that cannot regulate transcription. Defective regulation of the transcription process affects the development and function of many parts of the body. It is not known how nonfunctional carboxy-terminal domain phosphatase 1 protein results in the specific signs and symptoms of CCFDN.

Genetic Testing Information

• Genetic Testing Registry: Congenital cataracts-facial dysmorphism-neuropathy syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• CONGENITAL CATARACTS, FACIAL DYSMORPHISM, AND NEUROPATHY; CCFDN

Scientific Articles on PubMed

• PubMed

• Angelicheva D, Turnev I, Dye D, Chandler D, Thomas PK, Kalaydjieva L. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter. Eur J Hum Genet. 1999 Jul;7(5):560-6. doi: 10.1038/sj.ejhg.5200319. Citation on PubMed
• Kalaydjieva L, Chamova T. CTDP1-Related Congenital Cataracts, Facial Dysmorphism, and Neuropathy. 2010 Mar 2 [updated 2022 Oct 13]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK25565/ Citation on PubMed
• Kalaydjieva L. Congenital cataracts-facial dysmorphism-neuropathy. Orphanet J Rare Dis. 2006 Aug 29;1:32. doi: 10.1186/1750-1172-1-32. Citation on PubMed or Free article on PubMed Central
• Mastroyianni SD, Garoufi A, Voudris K, Skardoutsou A, Stefanidis CJ, Katsarou E, Gooding R, Kalaydjieva L. Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis. Eur J Pediatr. 2007 Jul;166(7):747-9. doi: 10.1007/s00431-006-0307-9. Epub 2006 Dec 30. Citation on PubMed
• Mullner-Eidenbock A, Moser E, Klebermass N, Amon M, Walter MC, Lochmuller H, Gooding R, Kalaydjieva L. Ocular features of the congenital cataracts facial dysmorphism neuropathy syndrome. Ophthalmology. 2004 Jul;111(7):1415-23. doi: 10.1016/j.ophtha.2003.11.007. Citation on PubMed
• Navarro C, Teijeira S. Neuromuscular disorders in the Gypsy ethnic group. A short review. Acta Myol. 2003 May;22(1):11-4. Citation on PubMed
• Shabo G, Scheffer H, Cruysberg JR, Lammens M, Pasman JW, Spruit M, Willemsen MA. Congenital cataract facial dysmorphism neuropathy syndrome: a clinically recognizable entity. Pediatr Neurol. 2005 Oct;33(4):277-9. doi: 10.1016/j.pediatrneurol.2005.04.011. Citation on PubMed
• Tournev I, Kalaydjieva L, Youl B, Ishpekova B, Guergueltcheva V, Kamenov O, Katzarova M, Kamenov Z, Raicheva-Terzieva M, King RH, Romanski K, Petkov R, Schmarov A, Dimitrova G, Popova N, Uzunova M, Milanov S, Petrova J, Petkov Y, Kolarov G, Aneva L, Radeva O, Thomas PK. Congenital cataracts facial dysmorphism neuropathy syndrome, a novel complex genetic disease in Balkan Gypsies: clinical and electrophysiological observations. Ann Neurol. 1999 Jun;45(6):742-50. Citation on PubMed
• Varon R, Gooding R, Steglich C, Marns L, Tang H, Angelicheva D, Yong KK, Ambrugger P, Reinhold A, Morar B, Baas F, Kwa M, Tournev I, Guerguelcheva V, Kremensky I, Lochmuller H, Mullner-Eidenbock A, Merlini L, Neumann L, Burger J, Walter M, Swoboda K, Thomas PK, von Moers A, Risch N, Kalaydjieva L. Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome. Nat Genet. 2003 Oct;35(2):185-9. doi: 10.1038/ng1243. Epub 2003 Sep 21. Citation on PubMed