Focal Dermal Hypoplasia (FDH)

What is Focal Dermal Hypoplasia (FDH)?

Also known as Goltz syndrome, this rare genetic condition affects mainly females.

90% of those diagnosed with the syndrome are female. Males may have only very mild symptoms. Generally the syndrome in its full form is fatal for males very early in their development.

As a multi-system disorder it affects multiple parts of the body in affected individuals.

There have been around 200-300 cases reported worldwide to date.

Syndrome Synonyms:
FDH Focal dermal hypoplasia Fodh; Dhof Goltz Syndrome Goltz-gorlin Syndrome Gorlin-Goltz syndrome

What gene changes cause Focal Dermal Hypoplasia (FDH)?

The syndrome is caused by changes to the PORCN syndrome. It is inherited in an X-linked dominant pattern.

With syndromes inherited in an X-linked dominant pattern, a mutation in just one of the copies of the gene, causes the syndrome. This can be in one of the female X chromosomes, and in the one X chromosomes males have. Males tend to have more severe symptoms than females.

What are the main symptoms of Focal Dermal Hypoplasia (FDH)?

Goltz syndrome is known as a multi system disorder, meaning it affects many different parts of the body.

The main syndromes affect the skin of affected individuals, as well as the hands, feet and eyes.

These symptoms might include papilloma, or wart-like growths that develop in individuals with age. They can be found all over the body including the gums, tongue, lips, nose, genitalia and anus.

Individuals may have issues with either excessive sweating or conversely an inability to sweat, particularly on their hands and feet.

Other physical features of the syndrome include drooping eyelids, defects in the iris or retina, small or missing eyes, widely spaced eyes, and crossed eyes. Individuals may have missing digits, or digits that have fused together. Features relating to the mouth might include dental and teeth abnormalities, and a cleft lip and palate.

Possible clinical traits/features:
Mixed hearing impairment, Multicystic kidney dysplasia, Abnormal adipose tissue morphology, Abnormality of dental morphology, Abnormality of dental enamel, Abdominal pain, Abnormal localization of kidney, Neoplasm of the skeletal system, Narrow nasal bridge, Low-set ears, Low-set, posteriorly rotated ears, Lower limb asymmetry, Linear hyperpigmentation, Labial hypoplasia, Joint laxity, Iris coloboma, Microphthalmia, Midclavicular aplasia, Midclavicular hypoplasia, Myelomeningocele, Intestinal malrotation, Intellectual disability, Inguinal hernia, Hydronephrosis, Hydrocephalus, Horseshoe kidney, Hiatus hernia, Short stature, Opacification of the corneal stroma, Cognitive impairment, Short finger, Visual impairment, Short phalanx of finger, Hypermelanotic macule, Short ribs, Hypoplastic nipples, Hypodontia, Hypoplasia of dental enamel, Thin skin, Telangiectasia, Postaxial hand polydactyly, Pointed chin, Foot polydactyly, Hand polydactyly, Nystagmus, Optic atrophy, Osteopathia striata, Foot oligodactyly, Hand ol

How does someone get tested for Focal Dermal Hypoplasia (FDH)?

The initial diagnosis of Focal Dermal Hypoplasia syndrome can begin with facial analysis screening, as offered by FDNA Telehealth, which can identify the key markers of the syndrome and outline the need for further testing. If further testing is recommended what will follow is a consultation with a genetic counselor and then a geneticist. These consultations will usually involve a comprehensive review of the patient’s medical history, a generational family history documenting health issues and genetic conditions, and a detailed physical examination.

Medical information on Focal Dermal Hypoplasia (FDH)

Mixed hearing impairment, Multicystic kidney dysplasia, Abnormal adipose tissue morphology, Abnormality of dental morphology, Abnormality of dental enamel, Abdominal pain, Abnormal localization of kidney, Neoplasm of the skeletal system, Narrow nasal bridge, Low-set ears, Low-set, posteriorly rotated ears, Lower limb asymmetry, Linear hyperpigmentation, Labial hypoplasia, Joint laxity, Iris coloboma, Microphthalmia, Midclavicular aplasia, Midclavicular hypoplasia, Myelomeningocele, Intestinal malrotation, Intellectual disability, Inguinal hernia, Hydronephrosis, Hydrocephalus, Horseshoe kidney, Hiatus hernia, Short stature, Opacification of the corneal stroma, Cognitive impairment, Short finger, Visual impairment, Short phalanx of finger, Hypermelanotic macule, Short ribs, Hypoplastic nipples, Hypodontia, Hypoplasia of dental enamel, Thin skin, Telangiectasia, Postaxial hand polydactyly, Pointed chin, Foot polydactyly, Hand polydactyly, Nystagmus, Optic atrophy, Osteopathia striata, Foot oligodactyly, Hand ol

"The skin lesions are variable. There is congenital skin hypoplasia, which might be extensive and often involves the scalp. The skin lesions are often bilateral but asymmetrical over both lower limbs, initially red in colour, patchy and of different shapes and sizes. Later, fat might herniate through the areas of atrophy. In addition there are often areas of linear or reticular hyper- or hypopigmentation. Papillomas develop around the lips, gums or the side of the nose. Kore-Eda et al., (1995) reported a case where giant papillomas developed on the trunk and extremities. Scalp hair may be sparse or brittle and the nails are frequently dysplastic. The limb defects include syndactyly of fingers 3 and 4, polydactyly, or even missing fingers or part of a limb. The eyes are also frequently affected, mostly asymmetrically, with chorioretinal or iris colobomata, but unilateral anophthalmos has been reported. Lueder and Steiner (1995) reported a mother and daughter with subepithelial corneal opacities and prominent corneal nerves. They were said to have features of Goltz syndrome, but this was not well documented. Microcephaly and retardation are frequent. Severe facial clefting can occur (Sbroggio de Oliveira Rodini et al., (2006), and natal teeth have been reported (Dias et al., 2010).
Rodini et al., (1992) studied two probable cases without the typical skin lesions, but with signs of osteopathia striata. Irvine et al., (1996) reported a case with mediastinal dextropostion (presumably not true dextrocardia), intestinal malrotation, and duodenal atresia. Han et al., (2000) reported a case with truncus arteriosus, VSD, a massive diaphragmatic hernia and absence of the right kidney. The female infant reported by Pivnick et al., (1998) with thoracoabdominal schisis, diaphragmatic and severe limb defects might represent Goltz syndrome.
Giant cell tumors of bone have been reported (Borgers et al., 2014)
Most cases are female and inheritance is thought to be X-linked dominant with early intrauterine lethality in males. There have been two reports of father to daughter transmission (Larregue et al., 1971; Burgdorf et al., 1981). The latter family was restudied by Gorski (1991), looking at X-inactivation, and it was concluded that the father was most likely to be a mosaic.
Naritomi et al., (1992) reported two females with terminal Xp deletions. They had microphthalmia, cloudy corneae, mild linear skin lesions and agenesis of the corpus callosum. The authors felt that the clinical features overlapped with Aicardi and Goltz syndromes and suggested a contiguous gene syndrome.Very rarely, a myelomeningocele, hydrocephalus and Chiari malformation have been noted (Peters et al., 2014)
Zuffardi et al., (1989) a reported a girl with features of the condition who had a 9q32-qter deletion secondary to a maternal 4q35;9q32 translocation. She was found to have heterozygous deletion of COL5A1 and underexpression of alpha1 chains of type V collagen by fibroblasts (Ghiggeri et al., 1993). Bellosta et al., (1996) reported a family with 7 affected females. Cytogenetic analysis in two of these showed an apparent increase of structural chromosomal abnormalities in up to 5% of metaphases. Patel et al., (1997) reported a severely affected case detected by fetal ultrasound scans.
Fryssira et al., (2002) reported a male infant with overlapping features between Goltz and MIDAS syndrome. There was asymmetric polysyndactyly with severe sclerocornea of the right eye and persistent hypoplastic primary vitreous of the left eye. At three months there were erythematous and atrophic linear skin defects, however these were over the trunk and extremity, which would be unusual for MIDAS syndrome.
The gene has now been identified as PORCN a regulator of Wnt signaling (Grzeschik et al., 2007, Wang et al., 2007). Note the report by Maas et al., (2009) of 17 patients (14 had mutations and the 3 without were atypical). Two classically affected females had 3 affected females with thoracic and abdominal body wall defects resembling the pentalogy of Cantrell. A further case with the overlap between Goltz and the pentalogy of Cantrell was reported by Smigiel et al., (2011). The patiet, with a mutation, reported by Contreras-Capetillo et al., (2014) was clinically absolutely typical, but did not have focal dermal hypoplasia.
Wright et al. (2016) evaluated oral findings in 19 individuals with focal dermal hypoplasia. The authors reported that 80% of the affected individuals had anomalies of oral hard and/or soft tissue. Dental anomalies included vertical enamel grooving, peg-shaped tooth deformities, and enamel hypoplasia with or without discoloration. Cleft lip and cleft palate were present in 15% of the patients. Other findings included intraoral lipoma or papilloma. The patients frequently presented with speech problems or chewing difficulty.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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